bluuebunny/crossref_metadata_2025 huggingface dataset:
The Secret Nexus. A Case Study of Deviant Masons, Mafia and Corruption in Italy
Authors: Sergi Anna , Vannucci Alberto
Published: December 2022

This paper wishes to explore some characteristics of the relevant interconnections between mafias/mafiosi and masonic lodges/masons in the Italian context. The paper sets out to study these interconnections from a social science perspective rooted in sociological and neo-institutional studies of organised crime and mafias, but also in criminological approaches to social constructionism, in the form of symbols and narratives. We will present a case study to reflect on the roles that (deviant) masons can assume in contexts where both mafias’ and personal, political, or economic interests are at play. The case study shows how masonic alliances can augment networking and enforcing capabilities: we call this process masonic deviance amplification. Additionally, the case study confirms the constitutive power that narratives around the masonic world hold today in the Italian context.
Switching angle optimization and fault analysis of a multistring-multilevel inverter for renewable-energy-source applications
Authors: Savitha M , Nagaraja Rao S
Published: December 2022

In this paper, a multistring-multilevel inverter (M-MLI) for renewable-energy-source applications has been proposed with reduced switch count and harmonics along with single-switch fault analysis for various levels. It requires only ‘m+1’ power switches for ‘m’ voltage levels. The proposed work achieves the fine-tuning of switching angles using a metaheuristic technique, i.e. the teaching–learning-based optimization algorithm (TLBOA), to mitigate the total harmonic distortion (THD) of the M-MLI. Furthermore, the proposed TLBOA has been compared with conventional modulation techniques such as equal phase (EP), half-equal phase (HEP), near-level control (NLC) and Newton–Raphson (NR) to verify the effectiveness of TLBOA for various voltage levels in terms of % voltage-THD (%V-THD), computational time and methodology. By fine-tuning the switching angles, the %V-THD is improved significantly when compared with EP, HEP, NLC and NR modulation techniques. For an 11-level single-phase M-MLI, the %V-THD using TLBOA at 0.91 modulation index (MI) is 5.051%. The lower-order harmonics, i.e. 5, 7, 11 and 13, are eliminated to improve the power quality. Furthermore, MLIs are often prone to failure, resulting in waveform distortion. The extreme reduction in power quality impacts the load and significant damage is likely. The location of the open-circuit fault to be identified becomes more tedious under the faulty conditions with increased switch counts and voltage levels since the mathematical modelling fails to address the scenario in less computational time. Hence, the machine-learning approach, i.e. support vector machine (SVM) with Bayesian optimization, has been discussed to locate the faulty switch. Finally, the proposed M-MLI configuration has been modelled, simulated and validated using MATLAB® and Simulink®. The results of the M-MLI configuration have been verified for 7, 9 and 11 levels using TLBOA along with fault analysis using the SVM approach.
Effectiveness of diabetes education interventions in rural America: a systematic review
Authors: Jarvandi Soghra , Roberson Patricia , Greig Jamie , Upendram Sreedhar , Grion Joelle
Published: December 2022

The purpose of this systematic review is to summarize the characteristics of recent studies on diabetes education interventions in rural areas and identify the relative proportion of studies with characteristics of interest that showed a reduction in glycated hemoglobin (A1C). A systematic literature search was performed in Web of Science, PubMed and PsychInfo, using keywords and Medical Subject Heading terms. Articles conducted in rural areas of the United States tested an educational intervention for people with type 2 diabetes, and reported outcomes were identified. A total of 2762 articles were identified, of which 27 were included. Of the 27 articles, most were implemented in the Southeast (n = 13). Of the 21 interventions that measured A1C, 10 reported a statistically significant decrease in A1C. The proportion of studies with a significant A1C reduction was higher for the studies that used telehealth/online, delivered by a collaboration between health-care professionals and lay educators or included family or group components. Only three studies included their criteria in determining rurality. Future diabetes education interventions may consider including family members or group sessions, holding online sessions and partnering with local resources. Additionally, stronger research methods are needed to test practical and effective interventions to improve diabetes education in rural areas.
RcbHLH59-RcPRs module enhances salinity stress tolerance by balancing Na+/K+ through callose deposition in rose (Rosa chinensis)
Authors: Su Lin , Zhang Yichang , Yu Shuang , Geng Lifang , Lin Shang , Ouyang Lin , Jiang Xinqiang
Published: December 2022

Basic helix–loop–helix (bHLH) proteins play pivotal roles in plant growth, development, and stress responses. However, the molecular and functional properties of bHLHs have not been fully characterized. In this study, a novel XI subgroup of the bHLH protein gene RcbHLH59 was isolated and identified in rose (Rosa sp.). This gene was induced by salinity stress in both rose leaves and roots, and functioned as a transactivator. Accordingly, silencing RcbHLH59 affected the antioxidant system, Na +/K + balance, and photosynthetic system, thereby reducing salt tolerance, while the transient overexpression of RcbHLH59 improved salinity stress tolerance. Additionally, RcbLHLH59 was found to regulate the expression of sets of pathogenesis-related (PR) genes in RcbHLH59-silenced (TRV-RcbHLH59) and RcbHLH59-overexpressing (RcbHLH59-OE) rose plants. The RcPR4/1 and RcPR5/1 transcript levels showed opposite changes in the TRV-RcbHLH59 and RcbHLH59-OE lines, suggesting that these two genes are regulated by RcbHLH59. Further analysis revealed that RcbHLH59 binds to the promoters of RcPR4/1 and RcPR5/1, and that the silencing of RcPR4/1 or RcPR5/1 led to decreased tolerance to salinity stress. Moreover, callose degradation- and deposition-related genes were impaired in RcPR4/1- or RcPR5/1-silenced plants, which displayed a salt tolerance phenotype by balancing the Na+/K+ ratio through callose deposition. Collectively, our data highlight a new RcbLHLH59-RcPRs module that positively regulates salinity stress tolerance by balancing Na+/K+ and through callose deposition in rose plants.
Apparent jejunal amino acid digestibility, gut morphology, and the expression of intestinal amino acid transporters in pigs fed protein or free amino acids
Authors: Eugenio Francis Amann , van Milgen Jaap , Duperray Joël , Sergheraert Renaud , Le Floc’h Nathalie
Published: December 2022

Dietary amino acids (AA) supplied as protein or in free form are not only digested and absorbed at different rates but can also induce differences in the intestinal physiology of pigs. We compared the apparent jejunal AA digestibility, intestinal morphology, and gene expression of AA transporters of pigs fed diets providing different forms of AA. Thirty growing pigs (33.7 ± 4.1 kg) were fed one of three experimental diets that provided AA either as protein from feather meal (INT), as free AA and small peptides obtained by extensive acid hydrolysis of feathers (HYD), or as a mix of individual purified AA with the same AA profile as HYD (FAA). Pigs were fed the same quantity of feed, energy, and AA. After 14 d, pigs were slaughtered 3 h after feeding a meal with indigestible markers. Digesta and tissue were collected from different sections of the small intestine. Jejunal digesta was used to measure apparent jejunal digestibility of AA. Samples of the duodenum, jejunum, and ileum were used to measure intestinal morphology and the gene expression of intestinal AA transporters. The measured apparent jejunal digestibility of AA of INT was lower compared to HYD and FAA (P < 0.05). The apparent jejunal digestibility of Cys, Gly, His, Met, and Pro was lower for FAA compared to HYD (P < 0.05). This may be due to the small peptides in HYD, which are absorbed faster than individual AA. The villi area in the ileum of HYD fed pigs was the highest (P < 0.05) among the treatments, which may be associated with the reabsorption of endogenous proteins, which occurs mostly in the ileum. In the duodenum, HYD and FAA had lower expression of PepT1 (P < 0.01) probably due to the rapid transit time of digesta compared to INT fed pigs. Pigs fed HYD expressed more ASCT2 (P = 0.02) and CAT-1 (P = 0.04) in the jejunum compared to the pigs fed the other diets. The expression of these transporters along the intestine depended on the relative abundance of readily absorbable dietary AA. Results showed that dietary AA form can have an influence on the morphology and on the expression of different AA transporters along the different sections of the small intestine.
The growth, respiration, and reproduction of crustaceans: a synthesis through the Gill-Oxygen Limitation Theory (GOLT)
Authors: Pauly Daniel , Amarasinghe Upali S , Chu Elaine , Freire Kátia Meirelles Felizola , Vázquez Elsa , Butler Mark J
Published: December 2022

Gill surface area (S) and respiration (R) in juvenile and adult crustaceans scale with their body weight (W) such that S ∝ R ∝ Wd, with d ranging mostly between 0.6 and 0.9, but always <1, as in other water-breathing ectotherms (WBE). The growth of adult crustaceans therefore approaches an asymptote, whether or not seasonal growth oscillations are explicitly considered in the model used to describe that growth (e.g., von Bertalanffy growth function). On the other hand, the variation in asymptotic size (L∞ or W∞) among crustaceans is primarily determined by water temperature, which impacts on the oxygen requirements of WBE. Through multiple examples, this and related aspects of the Gill-Oxygen Limitation Theory (GOLT), first developed for fishes and later extended to other WBE, are shown to also apply to the growth of a wide range of crustacean taxa. The GOLT also explains certain aspects of crustacean reproduction, such as the relationship between size at first maturity and maximum size, and, possibly, the feature that female crustaceans hold their eggs outside of their bodies instead of internally.
Trade Law 4.0: Are We There Yet?
Authors: Burri Mira
Published: December 2022

This article showcases the transformation of the regulatory topic of electronic commerce from trade law 2.0 (as the mere trade in goods and services online) towards trade law 4.0 (as the regulation of the data-driven economy). It traces the dynamics of digital trade regulation in the past decade in a complex geopolitical setting by looking at some broad trends, as well as at distinct regulatory models endorsed by preferential trade agreements (PTAs). The article then goes back to the multilateral forum of the World Trade Organization (WTO) and reveals how PTAs have worked as regulatory laboratories and asks whether their results can be translated to the WTO. The enquiry highlights the possibilities and the constraints of the multilateral forum in this context, as well as seeks to uncover both legal innovation and path dependencies in the global digital trade rule-making landscape.
Engagement with partisan Russian troll tweets during the 2016 U.S. presidential election: a social identity perspective
Authors: Rains Stephen A , Harwood Jake , Shmargad Yotam , Kenski Kate , Coe Kevin , Bethard Steven
Published: December 2022

Operatives working for the Russian Internet Research Agency (IRA) infiltrated social media with the goal of disrupting the 2016 U.S. presidential election. We investigate how these operatives or “trolls” leveraged partisan political identities in discussing presidential candidates and parties on Twitter. Adopting a social identity lens, we conceptualize retweeting troll content as a form of identity performance and examine the message properties that led troll tweets to resonate among Twitter users. The findings highlight the importance of partisan trolls’ persistence in tweeting about candidates and parties as well as their discussion of the political outgroup and incivility in the form of name-calling. The results collectively indicate that Twitter users were sensitive to messages generated by IRA trolls and responded in a manner consistent with identity performance.
A Pilot Medic-based Assessment of the Novel Handheld LifeFlow Device for Rapid Infusion of Blood Products
Authors: Mongold Sarah M , Mancha Fabiola , Weymouth Wells L , Maddry Joseph K , Schauer Steven G
Published: December 2022

Introduction

Uncontrolled hemorrhage remains the leading cause of preventable death in the prehospital, combat setting. Treatment guidelines emphasize immediate hemorrhage control and early resuscitation with whole blood or blood products. Current methods for the delivery of blood products are often insufficient to provide trauma resuscitation. The novel LifeFlow device is a hand-powered device that can rapidly infuse fluids, including blood products. However, successful use of this device in the hands of the intended end user has not been demonstrated.

Materials and Methods

We conducted a pilot study to assess how quickly and effectively medics could set up the LifeFlow device and infuse mock blood products into a casualty. They were provided with a brief block of instruction (<10 min) and the opportunity to handle the device. The time to set up the device and proportion of successful completion were recorded. Participants were surveyed regarding the use of the device including post-study interview.

Results

Forty medics, who were recruited and eligible to participate, completed the study procedures. All medics were able to successfully set up the device and perform the infusion. We had two instances of fluid leakage owing to malfunctions with the simulation arm, not the LifeFlow device. The mean time to device setup was 112 s (95% confidence interval [CI], 101-124). The mean time for infusion of 500 mL of fluid was 94 s (95% CI, 83-105). The mean time for all procedures was 197 s (95% CI, 178-213). On product feedback, they generally found it easier to use, easy to manipulate, possessing a useful grip, easily set up, and requiring minimal training.

Conclusions

The medics were able to reliably assemble and use the LifeFlow rapid infusion device. However, there were concerns about the packaging and the single indication for the device.
Management of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Onboard a U.S. Navy Hospital Ship Amid a Global Omicron Surge
Authors: Ramchandar Nanda , Slayden Tanner , Garcia-Rivera Jose A , Crouch Daniel , Gallagher Kia , Harris David , Lane Alison , Ha Lawrence , Halliday Megan , Ruano Eddy , Treiber Daniel , Quast Timothy , Feinberg Jeffrey
Published: December 2022

Introduction

We present a real-world experience of a U.S. Navy Hospital Ship deployed amid a global Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surge and the challenges of navigating policy while maintaining a mission-focused itinerary in an operational environment.

Materials and Methods

We performed a chart review of SARS-CoV-2 cases from April 18 to September 20, 2022, within a closed population of fully vaccinated adults onboard the USNS Mercy (T-AH 19) during the 5-month 2022 Pacific Partnership mission to Guam, Vietnam, Palau, Philippines, and the Solomon Islands.

Results

There were 123 total SARS-CoV-2 cases over the course of the mission, constituting 16.6% of the total crew (123/741). No more than 14 service members were actively infected at a given time (1.9%, 14/741). The average number of active cases at any given time was 0.8 (1.9 SD, 0.1% [0.8/741]), and just 14 of these were shipboard secondary cases. No significant operational requirements of the ship were impacted by infection-related manning shortages, there were no hospitalizations, and all infected members experienced full recovery.

Conclusions

Despite ongoing cases throughout the majority of the mission, a healthy immunized crew experienced no serious cases and minimal impact on operational effectiveness.
Escherichia Coli: What Is and Which Are?
Authors: Cobo-Simón Marta , Hart Rowan , Ochman Howard
Published: December 2022

Escherichia coli have served as important model organisms for over a century—used to elucidate key aspects of genetics, evolution, molecular biology, and pathogenesis. However, defining which strains actually belong to this species is erratic and unstable due to shifts in the characters and criteria used to distinguish bacterial species. Additionally, many isolates designated as E. coli are genetically more closely related to strains of Shigella than to other E. coli, creating a situation in which the entire genus of Shigella and its four species are encompassed within the single species E. coli. We evaluated all complete genomes assigned to E. coli and its closest relatives according to the biological species concept (BSC), using evidence of reproductive isolation and gene flow (i.e., homologous recombination in the case of asexual bacteria) to ascertain species boundaries. The BSC establishes a uniform, consistent, and objective principle that allows species-level classification across all domains of life and does not rely on either phenotypic or genotypic similarity to a defined type-specimen for species membership. Analyzing a total of 1,887 sequenced genomes and comparing our results to other genome-based classification methods, we found few barriers to gene flow among the strains, clades, phylogroups, or species within E. coli and Shigella. Due to the utility in recognizing which strains constitute a true biological species, we designate genomes that form a genetic cohesive group as members of E. coliBIO.
Trypanosoma brucei RRP44: a versatile enzyme for processing structured and non-structured RNA substrates
Authors: Cesaro Giovanna , da Soler Heloisa Tramontin , Guerra-Slompo Eloise Pavão , Haouz Ahmed , Legrand Pierre , Zanchin Nilson Ivo Tonin , Guimaraes Beatriz Gomes
Published: December 2022

Rrp44/Dis3 is a conserved eukaryotic ribonuclease that acts on processing and degradation of nearly all types of RNA. It contains an endo- (PIN) and an exonucleolytic (RNB) domain and, its depletion in model organisms supports its essential function for cell viability. In Trypanosoma brucei, depletion of Rrp44 (TbRRP44) blocks maturation of ribosomal RNA, leading to disruption of ribosome synthesis and inhibition of cell proliferation. We have determined the crystal structure of the exoribonucleolytic module of TbRRP44 in an active conformation, revealing novel details of the catalytic mechanism of the RNB domain. For the first time, the position of the second magnesium involved in the two-metal-ion mechanism was determined for a member of the RNase II family. In vitro, TbRRP44 acts preferentially on non-structured uridine-rich RNA substrates. However, we demonstrated for the first time that both TbRRP44 and its homologue from Saccharomyces cerevisiae can also degrade structured substrates without 3’-end overhang, suggesting that Rrp44/Dis3 ribonucleases may be involved in degradation of a wider panel of RNA than has been assumed. Interestingly, deletion of TbRRP44 PIN domain impairs RNA binding to different extents, depending on the type of substrate.
Structural basis of DNA polymerase θ mediated DNA end joining
Authors: Li Chuxuan , Zhu Hanwen , Jin Shikai , Maksoud Leora M , Jain Nikhil , Sun Ji , Gao Yang
Published: December 2022

DNA polymerase θ (Pol θ) plays an essential role in the microhomology-mediated end joining (MMEJ) pathway for repairing DNA double-strand breaks. However, the mechanisms by which Pol θ recognizes microhomologous DNA ends and performs low-fidelity DNA synthesis remain unclear. Here, we present cryo-electron microscope structures of the polymerase domain of Lates calcarifer Pol θ with long and short duplex DNA at up to 2.4 Å resolution. Interestingly, Pol θ binds to long and short DNA substrates similarly, with extensive interactions around the active site. Moreover, Pol θ shares a similar active site as high-fidelity A-family polymerases with its finger domain well-closed but differs in having hydrophilic residues surrounding the nascent base pair. Computational simulations and mutagenesis studies suggest that the unique insertion loops of Pol θ help to stabilize short DNA binding and assemble the active site for MMEJ repair. Taken together, our results illustrate the structural basis of Pol θ-mediated MMEJ.
POT-3 preferentially binds the terminal DNA-repeat on the telomeric G-overhang
Authors: Yu Xupeng , Gray Sean , Ferreira Helder C
Published: December 2022

Eukaryotic chromosomes typically end in 3′ telomeric overhangs. The safeguarding of telomeric single-stranded DNA overhangs is carried out by factors related to the protection of telomeres 1 (POT1) protein in humans. Of the three POT1-like proteins in Caenorhabditis elegans, POT-3 was the only member thought to not play a role at telomeres. Here, we provide evidence that POT-3 is a bona fide telomere-binding protein. Using a new loss-of-function mutant, we show that the absence of POT-3 causes telomere lengthening and increased levels of telomeric C-circles. We find that POT-3 directly binds the telomeric G-strand in vitro and map its minimal DNA binding site to the six-nucleotide motif, GCTTAG. We further show that the closely related POT-2 protein binds the same motif, but that POT-3 shows higher sequence selectivity. Crucially, in contrast to POT-2, POT-3 prefers binding sites immediately adjacent to the 3′ end of DNA. These differences are significant as genetic analyses reveal that pot-2 and pot-3 do not function redundantly with each other in vivo. Our work highlights the rapid evolution and specialisation of telomere binding proteins and places POT-3 in a unique position to influence activities that control telomere length.
DNA–protein cross-links between abasic DNA damage and mitochondrial transcription factor A (TFAM)
Authors: Xu Wenyan , Tang Jin , Zhao Linlin
Published: December 2022

In higher eukaryotic cells, mitochondria are essential organelles for energy production, metabolism, and signaling. Mitochondrial DNA (mtDNA) encodes 13 protein subunits for oxidative phosphorylation and a set of tRNAs and rRNAs. mtDNA damage, sourced from endogenous chemicals and environmental factors, contributes to mitochondrial genomic instability, which has been associated with various mitochondrial diseases. DNA–protein cross-links (DPCs) are deleterious DNA lesions that threaten genomic integrity. Although much has been learned about the formation and repair of DPCs in the nucleus, little is known about DPCs in mitochondria. Here, we present in vitro and in cellulo data to demonstrate the formation of DPCs between a prevalent abasic (AP) DNA lesion and a DNA-packaging protein, mitochondrial transcription factor A (TFAM). TFAM cleaves AP-DNA and forms DPCs and single-strand breaks (SSB). Lys residues of TFAM are critical for the formation of TFAM-DPC and a reactive 3′-phospho-α,β-unsaturated aldehyde (3′pUA) residue on SSB. The 3′pUA residue reacts with two Cys of TFAM and contributes to the stable TFAM-DPC formation. Glutathione reacts with 3′pUA and competes with TFAM-DPC formation, corroborating our cellular experiments showing the accumulation of TFAM-DPCs under limiting glutathione. Our data point to the involvement of TFAM in AP-DNA turnover and fill a knowledge gap regarding the protein factors in processing damaged mtDNA.
Are Fatwas Dispensable? Examining the Contemporary Relevance and Authority of Fatwas in Australia
Authors: Whyte Shaheen
Published: December 2022

Fatwas play a central role in the articulation and contextualization of Islamic law. Despite its lofty status within Islam’s juristic tradition, the authoritative value and function of fatwas in contemporary Muslim societies is undergoing significant change. Whereas historical fatwas generated immense solidarity within Islam’s legal schools and traditional ulama (religious scholars), Muslims today are confronted with an unprecedented supply of fatwas from various religious actors, institutions and digital platforms vying to speak for Islam. Using Australia as a case study, this article investigates the role, demand, and relevance of fatwas in Australia. It draws on empirical fieldwork conducted between 2018 and 2019 with Muslim religious actors including imams/sheikhs, educators, academics and members of the Australian Muslim community. The findings show Australian Muslims are largely sceptical about the relevance and credibility behind fatwa-making in Australia. Among the findings, participants demand greater scholarly expertise, legal analysis, and institutional output in the production of fatwas. Participants additionally expressed desire to establish locally based fatwa councils with the ability to produce context-specific fatwas for Australian Muslims.
Risk factors for haemodynamic compromise in multisystem inflammatory syndrome in children: a multicentre retrospective study
Authors: Kaidar Kfir , Dizitzer Yotam , Hashkes Philip J , Wagner-Weiner Linda , Tesher Melissa , Butbul Aviel Yonatan , Inbar Kanteman , Berkun Yackov , Eisenstein Eli M , Saied Mohamad Hamad , Goldzweig Ofra , Heshin-Bekenstein Merav , Ling Eduard , Feldon Michal , Levinsky Yoel , Tal Rotem , Harel Liora , Amarilyo Gil
Published: December 2022

Objectives

To identify predictors of a severe clinical course of multisystem inflammatory syndrome in children (MIS-C), as defined by the need for inotropic support.

Methods

This retrospective study included patients diagnosed with MIS-C (according to the CDC definition) in nine Israeli and one US medical centre between July 2020 and March 2021. Univariate and multivariate regression models assessed odds ratio (OR) of demographic, clinical, laboratory and imaging variables during admission and hospitalization for severe disease.

Results

Of 100 patients, 61 (61%) were male; mean age 9.65 (4.48) years. Sixty-five patients were hypotensive, 44 required inotropic support. Eleven patients with MIS-C fulfilled Kawasaki disease diagnostic criteria; 87 had gastrointestinal symptoms on admission. Echocardiographic evaluation showed 10 patients with acute coronary ectasia or aneurysm, and 37 with left ventricular dysfunction. In a univariate model, left ventricular dysfunction was associated with severe disease [OR 4.178 (95% CI 1.760, 9.917)], while conjunctivitis [OR 0.403 (95% CI 0.173, 0.938)] and mucosal changes [OR 0.333 (95% CI 0.119, 0.931)] at admission were protective. Laboratory markers for a severe disease course were low values of haemoglobin, platelets, albumin and potassium; and high leukocytes, neutrophils, troponin and brain natriuretic peptide. In multivariate analysis, central nervous system involvement and fever >39.5°C were associated with severe disease. Mucosal involvement showed 6.2-fold lower risk for severe disease. Low haemoglobin and platelet count, and elevated C-reactive protein and troponin levels were identified as risk factors for severe disease.

Conclusion

Key clinical and laboratory parameters of MIS-C were identified as risk factors for severe disease, predominantly during the disease course and not at the time of admission; and may prompt close monitoring, and earlier, more aggressive treatment decisions. Patients presenting with a Kawasaki-like phenotype were less likely to require inotropic support.
FAIRE‐MS reveals mitotic retention of transcriptional regulators on a proteome‐wide scale
Authors: Ye Bingyu , Shen Wenlong , Li Yanchang , Wang Dong , Zhang Yan , Li Ping , Yin Man , Wang Yahao , Xie Dejian , Shi Shu , Yao Tao , Chen Juncai , Xu Ping , Zhao Zhihu
Published: December 2022

Mitosis entails global and dramatic alterations, such as higher‐order chromatin organization disruption, concomitant with global transcription downregulation. Cells reliably re‐establishing gene expression patterns upon mitotic exit and maintaining cellular identities remain poorly understood. Previous studies indicated that certain transcription factors (TFs) remain associated with individual loci during mitosis and serve as mitotic bookmarkers. However, it is unclear which regulatory factors remain bound to the compacted mitotic chromosomes. We developed formaldehyde‐assisted isolation of regulatory elements‐coupled mass spectrometry (FAIRE‐MS) that combines FAIRE‐based open chromatin‐associated protein pull‐down and mass spectrometry (MS) to quantify the open chromatin‐associated proteome during the interphase and mitosis. We identified 189 interphase and mitosis maintained (IM) regulatory factors using FAIRE‐MS and found intrinsically disordered proteins and regions (IDP(R)s) are highly enriched, which plays a crucial role in liquid–liquid phase separation (LLPS) and chromatin organization during the cell cycle. Notably, in these IDP(R)s, we identified mitotic bookmarkers, such as CEBPB, HMGB1, and TFAP2A, and several factors, including MAX, HMGB3, hnRNP A2/B1, FUS, hnRNP D, and TIAL1, which are at least partially bound to the mitotic chromosome. Furthermore, it will be essential to study whether these IDP(R)s through LLPS helps cells transit from mitosis to the G1 phase during the cell cycle.
Single‐nucleus RNA and ATAC sequencing uncovers the molecular and cellular characteristics in the musk gland of Chinese forest musk deer (Moschus berezovskii)
Authors: Liu Chenmiao , Hong Tingting , Yu Lin , Chen Yuan , Wang Shuhui , Ren Zhanjun
Published: December 2022

The Chinese forest musk deer (FMD; Moschus berezovskii) is an endangered artiodactyl mammal. Musk secreted by the musk gland of male has extremely high economic and medicinal value. However, the molecular and cellular characteristics of the musk gland have not been studied. Here, we investigated the diversity and transcriptional composition of musk gland cell types and the effect of cell type‐specific chromatin accessibility on gene expression using single‐nucleus RNA sequencing (snRNA‐seq) and single‐nucleus ATAC sequencing (snATAC‐seq) association analysis. Based on uniform manifold approximation and projection (UMAP) analysis, we identified 13 cell types from the musk gland, which included two different acinar cells (cluster 0 and cluster 10). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that many pathways related to musk secretion were enriched in acinar cells. Our analysis also revealed acinar cell core transcription factors and core target genes, and further constructed acinar cell‐specific regulatory networks. In cluster 0, 11 core target genes (Nedd4l, Adcy9, Akr1c1, Vapb, Me1, Acsl1, Acss3, Srd5a1, Scnn1a, Acadm, and Nceh1) possibly related to musk secretion were regulated by 24 core transcription factors (SP3, NFIC, NR6A1, EHF, RUNX1, TFAP2A, RREB1, GRHL2, NFIB, ELF1, MAX, KLF5, REL, HES1, POU2F3, TFDP1, NR2C1, ATF7, MEIS1, NR4A2, NFIA, PBX1, ZNF652, and NFKB1). In cluster 10, four core target genes (Akr1c1, Pcca, Atp1b1, and Sgk1) possibly related to musk secretion were regulated by 10 core transcription factors (BARX2, EHF, PBX1, RUNX1, NFIB, FOXP1, KLF3, KLF6, ETV6, and NR3C2). Moreover, the credibility of snRNA‐seq and snATAC‐seq data was verified by fluorescence in situ hybridization and immunohistochemistry. Finally, cell communication analysis demonstrated that the two types of acinar cells mainly have communications in musk secretion‐related processes. In conclusion, we provided important insights and invaluable resources for the molecular and cellular characteristics of the musk gland, which will lay a foundation for the study of musk secretion mechanism in the future.
Modulation of TRPV4 protects against degeneration induced by sustained loading and promotes matrix synthesis in the intervertebral disc
Authors: Easson Garrett W. D. , Savadipour Alireza , Anandarajah Akila , Iannucci Leanne E. , Lake Spencer P. , Guilak Farshid , Tang Simon Y.
Published: December 2022

While it is well known that mechanical signals can either promote or disrupt intervertebral disc (IVD) homeostasis, the molecular mechanisms for transducing mechanical stimuli are not fully understood. The transient receptor potential vanilloid 4 (TRPV4) ion channel activated in isolated IVD cells initiates extracellular matrix (ECM) gene expression, while TRPV4 ablation reduces cytokine production in response to circumferential stretching. However, the role of TRPV4 on ECM maintenance during tissue‐level mechanical loading remains unknown. Using an organ culture model, we modulated TRPV4 function over both short‐ (hours) and long‐term (days) and evaluated the IVDs' response. Activating TRPV4 with the agonist GSK101 resulted in a Ca2+ flux propagating across the cells within the IVD. Nuclear factor (NF)‐κB signaling in the IVD peaked at 6 h following TRPV4 activation that subsequently resulted in higher interleukin (IL)‐6 production at 7 days. These cellular responses were concomitant with the accumulation of glycosaminoglycans and increased hydration in the nucleus pulposus that culminated in higher stiffness of the IVD. Sustained compressive loading of the IVD resulted in elevated NF‐κB activity, IL‐6 and vascular endothelial growth factor A (VEGFA) production, and degenerative changes to the ECM. TRPV4 inhibition using GSK205 during loading mitigated the changes in inflammatory cytokines, protected against IVD degeneration, but could not prevent ECM disorganization due to mechanical damage in the annulus fibrosus. These results indicate TRPV4 plays an important role in both short‐ and long‐term adaptations of the IVD to mechanical loading. The modulation of TRPV4 may be a possible therapeutic for preventing load‐induced IVD degeneration.
Excellence in Nursing Preceptorship-to-Hire, part 1
Authors: Letourneau Rayna , Robinson Leah , Cruz Vivien , Pryor Stacy , Williams Kaylyn , Bonamer Jennifer
Published: December 2022

An academic-practice partnership to recruit and retain nurses
Technique Tip: Using a Targeting Guide to Place Flexible Syndesmosis Fixation, in Ankle Fractures With a Dual Plate Construct
Authors: Manchanda Kshitij , Rodriguez-Materon Solangel , Raudes Adrianna , SanGiovanni Thomas Philip
Published: December 2022

Syndesmosis disruption alone or accompanying an ankle fracture is a frequent injury addressed by the foot and ankle surgeon. Reduction and fixation are usually performed with the use of implants as a tight rope and/or screw(s). When treating complex articular injuries requiring multiple buttress plates, the ability to enhance fixation with syndesmotic implants can be difficult in the presence of other hardware. We propose a technique using an anterior cruciate ligament targeting drill guide to precisely place syndesmotic fixation across both plates to achieve the ideal construct for stability. In this case, we used flexible fixation for the syndesmosis.

Level of Evidence: Diagnostic level V; expert opinion.
Extracorporeal Membrane Oxygenation Cannulation Timing in the Pediatric Myocarditis Population: An Exploratory Analysis From the Extracorporeal Life Support Organization Registry
Authors: Gutierrez Maria E. , Anders Marc , Guffey Danielle , Denfield Susan W. , Deshpande Shriprasad R. , Rajagopal Satish K. , Thiagarajan Ravi R. , Alexander Peta M. A. , Lasa Javier J.
Published: December 2022

OBJECTIVES:

Children presenting with acute myocarditis may experience rapid clinical deterioration requiring extracorporeal membrane oxygenation (ECMO); however, our understanding of best practices and timing of ECMO initiation are lacking. We explored the relationships between pre-cannulation factors and survival in this high-acuity patient population.

DESIGN:

Retrospective review of a large international registry. Primary outcome was survival to hospital discharge, stratified by incident cardiac arrest (CA) prior to ECMO and time to cannulation after intubation.

SETTING AND SUBJECTS:

The Extracorporeal Life Support Organization registry was queried for patients less than or equal to 18 years old receiving ECMO support for myocarditis between 2007 and 2018. Exclusion criteria included being nonindex runs, non-venoarterial ECMO or missing data points for main variables studied.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Population characteristics and survival were compared using t test, Wilcoxon rank-sum test, or Fisher exact test. Multivariable logistic regression was used for significant factors in the unadjusted logistic regression. Among 506 index ECMO runs in pediatric patients with myocarditis, survival for the cohort was 72%, with no difference between early and late eras (2007–2012 vs 2013–2018; p = 0.69). Survivors demonstrated higher pre-ECMO pH levels as well as shorter intubation-to-cannulation (ITC) times (3 hr [interquartile range (IQR)], 1–14 hr vs 6 hr [IQR, 2–20 hr]; p = 0.021). CA occurred within 24 hours prior to ECMO cannulation, including extracorporeal cardiopulmonary resuscitation, in 54% of ECMO runs (n = 273). Accounting for the interaction between pre-ECMO CA occurrence and ITC time, longer ITC time remained associated with lower survival for patients who did not experience a CA prior to ECMO, with adjusted odds ratio of 0.09 (IQR, 0.02–0.40; p = 0.002) for ITC time greater than or equal to 18 hours.

CONCLUSIONS:

The results of this multicenter analysis of ECMO utilization and outcomes for pediatric myocarditis suggest that patients approaching ECMO cannulation who have not experienced CA may have better survival outcomes if cannulated onto ECMO early after intubation.
Influence of severe neck angulation on hemodynamic and clinical outcomes following endovascular aneurysm repair: a hemodynamic analysis and a retrospective cohort study
Authors: Liu Yang , Qing Ming , Zhao Jichun , Huang Bin , Yang Yi , Zheng Tinghui , Yuan Ding
Published: December 2022

Background:

For patients with severe neck angulation (SNA), hemodynamic and clinical outcomes following endovascular aneurysm repair (EVAR) are still unclear. This study aimed to explore the influence of SNA on hemodynamic and clinical outcomes following EVAR.

Methods:

This study included a hemodynamic analysis and a retrospective cohort study from West China Hospital of Sichuan University between January 2011 and December 2020. The Cox regression model, inverse probability of treatment weighting (IPTW) analysis, sensitivity analysis, and subgroup analysis were applied. Primary outcome was type IA endoleak (T1AEL).

Results:

In this hemodynamic analysis, nine non-severe neck angulation (nSNA) and 16 SNA idealized models were constructed. We found a significant difference in drag force between SNA and nSNA models (7.016 ± 2.579 N vs. 4.283 ± 1.460 N, P = 0.008), and proximal neck angles were significantly associated with the magnitude of drag force (F = 0.082 × α–0.006 × β + 2.818, α: 95% confidence interval [CI] 0.070–0.094; P = 0.001; β: 95% CI −0.019 to 0.007; P = 0.319). In our cohort study, 514 nSNA patients (71.5 ± 8.5 years; 459 males) and 208 SNA patients (72.5 ± 7.8 years; 135 males) were included, with a median follow-up duration of 34 months (16–63 months). All baseline characteristics were well balanced after IPTW matching. We found that SNA was associated with a significant risk of adverse limb event (hazard ratio [HR] 2.18, 95% CI 1.09–3.12), yet was not associated with T1AEL, overall survival, or reintervention. In patients without proximal or distal additional procedures (DAP), subgroup analyses suggested a significant risk of T1AEL (Proximal: HR 5.25, 95% CI 1.51–18.23; Distal: HR 5.07, 95% CI 1.60–16.07) and adverse limb event (Proximal: HR 2.27, 95% CI 1.01–5.07; Distal: HR 2.91, 95% CI 1.30–6.54) in SNA patients. However, no noticeable difference was observed in patients with proximal or DAP.

Conclusions:

SNA has a critical influence on hemodynamic and clinical outcomes following EVAR. Appropriate additional procedures may be of great benefit to SNA patients.
Calcium-containing versus calcium-free replacement solution in regional citrate anticoagulation for continuous renal replacement therapy: a randomized controlled trial
Authors: Wei Tiantian , Tang Xin , Zhang Ling , Lin Li , Li Peiyun , Wang Fang , Fu Ping
Published: December 2022

Background:

A simplified protocol for regional citrate anticoagulation (RCA) using a commercial calcium-containing replacement solution, without continuous calcium infusion, is more efficient for use in continuous renal replacement therapy (CRRT). We aim to design a randomized clinical trial to compare the safety and efficacy between calcium-free and calcium-containing replacement solutions in CRRT with RCA.

Methods:

Of the 64 patients receiving RCA-based postdilution continuous venovenous hemodiafiltration (CVVHDF) enrolled from 2017 to 2019 in West China Hospital of Sichuan University, 35 patients were randomized to the calcium-containing group and 29 to the calcium-free replacement solution group. The primary endpoint was circuit lifespan and Kaplan–Meier survival analysis was performed. Secondary endpoints included hospital mortality, kidney function recovery rate, and complications. The amount of 4% trisodium citrate solution infusion was recorded. Serum and effluent total (tCa) and ionized (iCa) calcium concentrations were measured during CVVHDF.

Results:

A total of 149 circuits (82 in the calcium-containing group and 67 in the calcium-free group) and 7609 circuit hours (4335 h vs. 3274 h) were included. The mean circuit lifespan was 58.1 h (95% CI 53.8–62.4 h) in the calcium-containing group vs. 55.3 h (95% CI 49.7–60.9 h, log rank P = 0.89) in the calcium-free group. The serum tCa and iCa concentrations were slightly lower in the calcium-containing group during CRRT, whereas the postfilter iCa concentration was lower in the calcium-free group. Moreover, the mean amounts of 4% trisodium citrate solution infusion were not significantly different between the groups (171.1 ± 15.9 mL/h vs. 169.0 ± 15.1 mL/h, P = 0.49). The mortality (14/35 [40%] vs. 13/29 [45%], P = 0.70) and kidney function recovery rates of AKI patients (19/26, 73% vs. 14/24, 58%, P = 0.27) were comparable between the calcium-containing and calcium-free group during hospitalization, respectively. Six (three in each group) patients showed signs of citrate accumulation in this study.

Conclusions:

When compared with calcium-free replacement solution, RCA-based CVVHDF with calcium-containing replacement solution had a similar circuit lifespan, hospital mortality and kidney outcome. Since the calcium-containing solution obviates the need for a separate venous catheter and a large dose of intravenous calcium solution preparation for continuous calcium supplementation, it is more convenient to be applied in RCA-CRRT practice.

Registration:

Chinese Clinical Trial Registry (
www.chictr.org.cn
, ChiCTR-IPR-17012629)
Signaling pathways of adipose stem cell-derived exosomes promoting muscle regeneration
Authors: Zhu Aoxuan , Liu Na , Shang Yujia , Zhen Yonghuan , An Yang
Published: December 2022

Severe muscle injury is still a challenging clinical problem. Exosomes derived from adipose stem cells (ASC-exos) may be a potential therapeutic tool, but their mechanism is not completely clear. This review aims to elaborate the possible mechanism of ASC-exos in muscle regeneration from the perspective of signal pathways and provide guidance for further study. Literature cited in this review was acquired through PubMed using keywords or medical subject headings, including adipose stem cells, exosomes, muscle regeneration, myogenic differentiation, myogenesis, wingless/integrated (Wnt), mitogen-activated protein kinases, phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/Akt), Janus kinase/signal transducers and activators of transcription, and their combinations. We obtained the related signal pathways from proteomics analysis of ASC-exos in the literature, and identified that ASC-exos make different contributions to multiple stages of skeletal muscle regeneration by those signal pathways.
Does a large prostate size, small lesion volume, or long needle distance from the probe to the lesion reduce magnetic resonance imaging–targeted cancer detection?
Authors: Bevill Mark D. , Drobish Justin N. , Flynn Kevin J. , Rajput Maheen , Metz Catherine , Tracy Chad R. , Gellhaus Paul T.
Published: December 2022

Background

We aimed to evaluate whether large prostate size, small lesion volume, or long lesion distance from the ultrasound probe tip would decrease cancer detection in transrectal magnetic resonance imaging (MRI)–targeted biopsies.

Materials and methods

Patients who underwent MRI-targeted biopsy at our institution between May 2017 and August 2019 were enrolled in a prospective database. Three to 5 cores were obtained from ≥2 prostate imaging reporting and data system v2 lesions. A multivariable model was created that included needle distance to the lesion, prostate specific antigen, prostate imaging reporting and data system, lesion volume, and prostate volume.

Results

A total of 377 patients with 533 lesions underwent a biopsy during the study period. A total of 233 (44%) lesions were positive for prostate cancer, and 173 (32%) lesions had clinically significant prostate cancer. The mean needle distance to the lesion was 11.7 mm (interquartile range, 7.6–15.5 mm). The likelihood of obtaining a positive core on biopsy decreased as the distance from the ultrasound probe increased for all prostate cancers and clinically significant prostate cancer (p = 0.018 and p = 0.004, respectively). Every 10 mm from the rectum, there was an 8%–10% decrease in the rate of cancer detection. Similarly, as the prostate volume increased, the odds of obtaining a positive core also decreased (p = 0.039). There was no significant association between the lesion size and amount of cancer obtained on biopsy.

Conclusions

Our data showed that transrectal MRI-targeted biopsy cancer detection modestly decreased the lesion from the ultrasound probe and with a large prostate volume but could not prove that lesion volume was a significant predictor of the amount of cancer detected.
Antibias Efforts in United States Maternity Care: A Scoping Review of the Publicly Funded Health Equity Intervention Pipeline
Authors: Garrett Sarah B. , Walia Anjali , Miller Fiona , Tahir Peggy , Jones Linda , Harris Julie , Powell Breezy , Chambers Brittany , Simon Melissa A.
Published: December 2022

Antibias training is increasingly identified as a strategy to reduce maternal health disparities. Evidence to guide this work is limited. We conducted a community-guided scoping review to characterize new antibias research. Four of 508 projects met our criteria: US-based, publicly funded, initiated from January 1, 2018 to June 30, 2022, and featuring an intervention to reduce bias or racism in maternal health care providers. Training was embedded in multicomponent interventions in 3 projects, limiting its evaluation as a stand-alone intervention. Major public funders have sponsored a few projects to advance antibias training research in maternal health. More support is needed to develop a rigorous and scalable evidence base.