bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosome Structural Rearrangements in Invasive Haplodiploid Ambrosia Beetles Revealed by the Genomes of Euwallacea fornicatus (Eichhoff) and Euwallacea similis (Ferrari) (Coleoptera, Curculionidae, Scolytinae)
Authors: Bickerstaff James R M , Walsh Tom , Court Leon , Pandey Gunjan , Ireland Kylie , Cousins David , Caron Valerie , Wallenius Thomas , Slipinski Adam , Rane Rahul , Escalona Hermes E
Published: October 2024

Bark and ambrosia beetles are among the most ecologically and economically damaging introduced plant pests worldwide. Life history traits including polyphagy, haplodiploidy, inbreeding polygyny, and symbiosis with fungi contribute to their dispersal and impact. Species vary in their interactions with host trees, with many attacking stressed or recently dead trees, such as the globally distributed Euwallacea similis (Ferrari). Other species, like the Polyphagous Shot Hole Borer Euwallacea fornicatus (Eichhoff), can attack over 680 host plants and is causing considerable economic damage in several countries. Despite their notoriety, publicly accessible genomic resources for Euwallacea Hopkins species are scarce, hampering our understanding of their invasive capabilities as well as modern control measures, surveillance, and management. Using a combination of long and short read sequencing platforms, we assembled and annotated high quality (BUSCO > 98% complete) pseudo-chromosome-level genomes for these species. Comparative macrosynteny analysis identified an increased number of pseudo-chromosome scaffolds in the haplodiploid inbreeding species of Euwallacea compared to diploid outbred species, due to fission events. This suggests that life history traits can impact chromosome structure. Further, the genome of E. fornicatus had a higher relative proportion of repetitive elements, up to 17% more, than E. similis. Metagenomic assembly pipelines identified microbiota associated with both species including Fusarium fungal symbionts and a novel Wolbachia strain. These novel genomes of haplodiploid inbreeding species will contribute to the understanding of how life history traits are related to their evolution and to the management of these invasive pests.
Increased Evolutionary Rate in the Z chromosome of Sympatric and Allopatric Species of Morpho Butterflies
Authors: López Villavicencio Manuela , Ledamoisel Joséphine , Poloni Riccardo , Lopez-Roques Céline , Debat Vincent , Llaurens Violaine
Published: October 2024

Divergent evolution of genomes among closely related species is shaped by both neutral processes and ecological forces, such as local adaptation and reinforcement. These factors can drive accelerated evolution of sex chromosomes relative to autosomes. Comparative genomic analyses between allopatric and sympatric species with overlapping or divergent ecological niches offer insights into reinforcement and ecological specialization on genome evolution. In the butterfly genus Morpho, several species coexist in sympatry, with specialization across forest strata and temporal niches. We analyzed the genomes of eight Morpho species, along with previously published genomes of three others, to compare chromosomal rearrangements and signs of positive selection in the Z chromosome vs. autosomes. We found extensive chromosomal rearrangements in Z chromosome, particularly in sympatric species with similar ecological niches, suggesting a role for inversions in restricting gene flow at a postzygotic level. Z-linked genes also exhibited significantly higher dN/dS ratios than autosomal genes across the genus, with pronounced differences in closely related species living in sympatry. Additionally, we examined the evolution of eight circadian clock genes, detecting positive selection in Period, located on the Z chromosome. Our findings suggest that the Z chromosome evolves more rapidly than autosomes, particularly among closely related species, raising questions about its role in prezygotic and postzygotic isolation mechanisms.
Learning from employer experiences with paid leave policy expansions during the COVID-19 pandemic
Authors: Dow William H , Goodman Julia M , Lin Paloma , Park Paige
Published: October 2024

The United States does not have a federal policy offering employees paid leave. We study employer attitudes toward the Families First Coronavirus Response Act (FFCRA) federal emergency paid leave policies temporarily adopted during the COVID-19 pandemic to draw lessons for proposed permanent federal paid leave policies. We analyzed a 2021 survey of 300 San Francisco Bay Area employers to examine employers’ experiences with paid sick leave (PSL) and paid family leave (PFL) policies during the COVID-19 pandemic, along with their attitudes regarding FFCRA paid leave. Most firms reported that it was not difficult to comply with or seek reimbursement for FFCRA leave. Nevertheless, most smaller firms did report difficulty in understanding policy details, and many reported being unaware of FFCRA paid leave availability. FFCRA paid leave was broadly popular among firms aware of it: 64% supported (9% opposed) the PSL provisions, and 52% supported (12% opposed) PFL. However, support for permanent extension dropped to just over 40%, despite this Bay Area sample having long familiarity with California's state paid leave policies. We conclude that federal pandemic paid leave offers a potential model that could be refined for future paid leave policies, but support is mixed.
Effect of yeast probiotics in lactation and yeast cell wall prebiotic and Bacillus subtilis probiotic in nursery on lifetime growth performance, immune response, and carcass characteristics
Authors: Jenkins Abigail K , DeRouchey Joel M , Gebhardt Jordan T , Tokach Mike D , Woodworth Jason C , Goodband Robert D , Loughmiller Joseph A , Kremer Brian T
Published: October 2024

Twenty-eight mixed-parity sows (Line 241; DNA) and their offspring were used to evaluate live yeast supplementation during lactation with or without a pre/probiotic combination during the nursery period on lactation performance, lifetime growth performance, and immune response. On day 110 of gestation, sows were allotted to a lactation diet with or without a live yeast probiotic (0.10% Actisaf Sc 47 HR+; Phileo by Lesaffre, Milwaukee, WI). At weaning, their offspring (350 pigs; initially 6.1 ± 0.02 kg) were randomly assigned in a 2 × 2 factorial with main effects of sow treatment and nursery treatment consisting of a control diet or a diet with a yeast cell wall prebiotic and Bacillus subtilis probiotic (0.10% YB; Phileo by Lesaffre, Milwaukee, WI) fed for 42 d followed by common diets fed until marketing. Two nursery pens were combined into 1 finishing pen, such that there were 5 and 10 pigs per pen with 17 or 18 and 8 or 9 replications per treatment during the nursery and finishing periods, respectively. There were no significant effects of yeast supplementation on lactation performance (P ≥ 0.079). There was a sow × nursery diet interaction (P = 0.024) on nursery ADG. Pigs from yeast-fed sows had increased ADG when fed control nursery diets compared to pigs from control sows fed the control nursery diet with pigs fed pre/probiotic nursery diets intermediate, regardless of sow diet. Pigs from yeast-fed sows tended (P = 0.067) to have greater final body weight (BW) (day 165). A subset of pigs was sampled throughout their lifetime to determine serum porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae antibody sample-to-positive (S/P) ratios and percentage inhibition of Lawsonia intracellularis. There was a tendency for a PCV2 S/P ratio sow diet × day interaction (P = 0.097) where progeny from yeast-fed sows had higher PCV2 S/P ratios at 101 d of age compared to control sow progeny (P = 0.046). There was a PCV2 S/P ratio nursery diet × day interaction (P = 0.036) where pigs fed a pre/probiotic combination had reduced S/P ratios at 66, 78, and 162 d of age (P ≤ 0.022); however, at 22 d of age pigs fed a pre/probiotic combination tended to have an increased S/P ratio (P = 0.051). In conclusion, the effects of combining a yeast probiotic in lactation diets and a pre/probiotic in nursery diets were not additive. However, feeding a live yeast probiotic during lactation resulted in tendencies (P ≤ 0.10) for increased progeny final BW and hot carcass weight.
A chromosome-level genome assembly for the desert scorpion Mesobuthus przewalskii from Asian drylands
Authors: Su Yan-Kai , Xiu Ming-Hua , Yang Hao-Yan , Shi Cheng-Min
Published: October 2024

Scorpions are an ancient and charismatic group of arthropods with medical importance, but a high-quality reference genome for this group is still lacking. Here we perform whole-genome sequencing of Mesobuthus przewalskii, a desert scorpion endemic to the Taklimakan Desert. We combine PacBio HiFi sequencing and Hi-C chromosome conformation capturing to generate chromosomal-level, haplotype-resolved, and fully annotated genome assembly for this medically important scorpion. The assembly consists of two haplotypes (1,052.01 Mbp and 1,055.19 Mbp, respectively) reaching chromosome-level contiguity and >98% BUSCO (Benchmarking Universal Single-Copy Orthologs) completeness. Sequences were anchored in 13 chromosomes with a contig N50 of 34.44 Mbp and scaffold N50 of 81.43 Mbp. Several key genome features and the mitochondrial genome assembly were also provided. This genome represents the fifth but the most complete assembly for the order Scorpiones.
Winter torpor patterns of tricolored bats (Perimyotis subflavus) in the southeastern United States
Authors: Sirajuddin Pallavi , Loeb Susan C , Britzke Eric R , Peoples Brandon K , Jachowski David S
Published: October 2024

The Tricolored Bat (Perimyotis subflavus) has suffered significant population declines in much of its geographic range due to white-nose syndrome (WNS). Our aim was to describe the torpor patterns of tricolored bats within the southeastern United States to further our understanding of their winter ecology and potential susceptibility to WNS in currently unimpacted areas based on data from bats in both a WNS-affected hibernaculum and an unaffected hibernaculum. We placed temperature-sensitive radio transmitters on tricolored bats in a site in northwestern South Carolina that was WNS-positive and another site in northwestern Florida that was WNS-negative, and determined torpid and arousal skin temperatures (TSK), torpor bout duration (TBD), and arousal duration (AD) during 3 winters. Mean hibernacula temperature (TH) and vapor pressure deficit (VPDH) in both hibernacula were within the range of optimal Pseudogymnoascus destructans (Pd) growth (TH = 12.7 to 13.6 °C, VPDH = 0.028 to 0.059 kPA). Mean torpid TSK was 15.7 ± 0.1 °C and mean TBD was 4.1 ± 0.2 days across sites. Sex was the best predictor of TBD with males having significantly longer TBD than females. Torpid TSK was positively related to TH and negatively related to VPDH. Because the TSK of a bat was similar to the optimal growth temperatures of Pd, our findings suggest that even though winters in the southeastern United States are more benign than in other parts of the Tricolored Bat range, the warmer temperatures in southern hibernacula may provide optimal conditions for the growth of Pd. Greater understanding of the physiological responses of tricolored bats in hibernacula across their range will provide important data on the potential for WNS morbidity and mortality in unaffected areas and allow for a better distribution of resources for prevention and treatment of WNS.
Multiscale scanning with nuisance parameters
Authors: König Claudia , Munk Axel , Werner Frank
Published: October 2024

We develop a multiscale scanning method to find anomalies in a d-dimensional random field in the presence of nuisance parameters. This covers the common situation that either the baseline-level or additional parameters such as the variance are unknown and have to be estimated from the data. We argue that state of the art approaches to determine asymptotically correct critical values for multiscale scanning statistics will in general fail when such parameters are naively replaced by plug-in estimators. Instead, we suggest to estimate the nuisance parameters on the largest scale and to use (only) smaller scales for multiscale scanning. We prove a uniform invariance principle for the resulting adjusted multiscale statistic, which is widely applicable and provides a computationally feasible way to simulate asymptotically correct critical values. We illustrate the implications of our theoretical results in a simulation study and in a real data example from super-resolution STED microscopy. This allows us to identify interesting regions inside a specimen in a pre-scan with controlled family-wise error rate.
Unveiling the secrets of lotus seed longevity: insights into adaptive strategies for extended storage
Authors: Sun Heng , Xin Jia , Ullah Abid , Song Heyun , Chen Lin , Yang Dong , Deng Xianbao , Liu Juan , Ming Ray , Zhang Minghua , Yang Hui , Dong Gangqiang , Yang Mei
Published: October 2024

Seed longevity is crucial for long-term storage, but prolonged unfavorable conditions can lead to loss of viability. This study integrated theoretical and experimental techniques to elucidate the inherent mechanisms underlying the unique ability of lotus seeds to maintain stable viability over many years. Transcriptome analysis and microscopy revealed a sturdy structure of the lotus seed pericarp, which predominantly expressed cellulose synthase genes involved in cell wall biogenesis. The cotyledon serves as a nutrient source for seeds during long-term storage. Additionally, the inactivation of chlorophyll degradation pathways may allow for the retention of chlorophyll in the lotus seed plumule, potentially enhancing the environmental adaptability of lotus seedlings. Reduced abundance of transcripts corresponding to heat shock protein genes could impact protein processing and consequently diminish the vitality of aging lotus seeds. Moreover, an expansion in the number of seed maturation and defense response genes was observed in the lotus genome compared with 11 other species, which might represent an adaptive strategy against long-term adverse storage conditions. Overall, these findings are crucial for understanding the mechanisms underlying lotus seed longevity and may inform future improvements in the extended storage periods of seed crops.
Health Literacy and Health-Related Habits among Conscripts in the Norwegian Armed Forces—A Cross-Sectional Survey
Authors: Vejrup Kristine , Engel Tim Niklas , Lillegård Hanne Johansen , Strand Sara Kristine , Stein Linda , Olsen-Bergem Heming
Published: October 2024

Introduction

Although health information is widely available to the Norwegian population a lack of health literacy is still common and considered a public health challenge. However, there is limited information on the health literacy of the adolescent population in Norway. The purpose of this pilot study was to assess health literacy and self-reported health habits among soldiers in basic military training, both in field, camp, and home settings. Furthermore, we aimed to investigate which health habits characterize soldiers with inadequate health literacy.

Methods

An electronic questionnaire was sent out to conscripts who completed first-time military service in 2022 and was answered by 2,225 conscripts. Descriptive statistics were performed using cross-tabulations, correlations, and chi-squared tests. The survey is part of an internal quality study of the Norwegian Armed Forces routines. It is approved by the Norwegian Armed Forces joint medical services.

Results

In the study population, 43% scored inadequate health literacy on the European Health Literacy Survey Questionnaire-Q12 (HLS-Q12), and 57% scored adequate health literacy. We found a significant difference between those having inadequate and adequate HLS-Q12 scores in categories of self-rated health habits of oral health and diet with lower scores in the inadequate score group. The use of tobacco during field exercise in camp and at home was higher in the group of conscripts with adequate health literacy scores. The conscripts generally reported a lower standard of health habits during field exercises with significantly less brushing and flossing, higher use of tobacco products and higher consumption of energy drinks and sugary snacks compared to reported habits in camp and at home.

Conclusion

The results from our study suggest that the conscripts in the Norwegian Armed Forces have a lower health literacy than the general population, and this is reflected in reported higher frequency of unhealthy habits in service settings than at home. The Armed Forces have an opportunity to take responsibility to optimize the health skills of their soldiers and to encourage them to make informed decisions about their own health. Improved adaptation to the national recommendations regarding nutrition, tobacco use, and oral health are areas having the potential to greatly improve the overall health habits of conscripts.
Utility of the Vestibular/Ocular Motor Screening in Military Medicine: A Systematic Review
Authors: Hoppes Carrie W , Garcia de la Huerta Tomas , Faull Stefanie , Weightman Margaret , Stojak Margaret , Dibble Leland , Pelo Ryan M , Fino Peter C , Richard Holly , Lester Mark , King Laurie A
Published: October 2024

Introduction

The Vestibular/Ocular Motor Screening (VOMS) was created as a brief clinical screening tool for identifying vestibular and ocular motor symptoms and impairments post-concussion. It was found to have predictive validity in correctly identifying concussed athletes from healthy controls. In 2018, the Military Acute Concussion Evaluation 2 (MACE2) replaced the original Military Acute Concussion Evaluation (MACE); the most prominent change between the MACE and MACE2 was the addition of the VOMS. Despite its adoption into military medicine, it is not known if the addition of the VOMS to the MACE2 is acutely helpful, and if it provides additional information for diagnosis, prognosis, and/or management. The purposes of this systematic review were: (1) to determine the utility of the VOMS in correctly identifying concussed individuals, particularly as it pertains to military medicine; (2) to explore the extent to which the VOMS can inform concussion prognosis; and (3) to establish the value of the VOMS as a measure for monitoring the evolution of symptoms throughout a service member’s course of care.

Materials and Methods

A comprehensive search of PubMed was performed from January 1, 2014 through August 16, 2023. Articles were included if they researched concussion or a related health condition or healthy controls and administered the VOMS. Articles were excluded if they discussed health conditions other than concussion; did not administer the VOMS; or were written in languages other than English. The tools used to assess methodological quality and risk of bias varied according to study design. Articles were classified into three primary domains: diagnosis, prognosis, and/or rehabilitation/recovery over time.

Results

A total of 231 articles were retrieved and 3 were duplicates, leaving 228 articles for review. Of the 228 articles screened, 100 relevant full-text articles were assessed for eligibility. Fifty-nine articles met our inclusion and exclusion criteria while the other 41 articles were rejected. Thirty-two articles helped to inform diagnosis, 15 prognosis, and 16 rehabilitation/recovery over time.

Conclusions

The VOMS had excellent internal consistency and moderate to good test-retest reliability; however, a false-positive rate of 21.9% was found. Most studies indicated that a positive VOMS was associated with a delayed recovery. Several studies indicated that VOMS scores improved with targeted, active interventions and/or a symptom-guided progressive return to activity. The greatest limitation was the paucity of published evidence in the military population. More research is needed on the use of the VOMS in service members.
Sex Differences in Subclinical Psychotic Experiences: The Role of Daily-Life Social Interactions
Authors: Akcaoglu Zeynep , Myin-Germeys Inez , Vaessen Thomas , Janssens Julie J , Wampers Martien , Bamps Eva , Lafit Ginette , Kirtley Olivia J , Achterhof Robin
Published: October 2024

Background and Hypothesis

Sex differences in psychosis are reported across the psychosis spectrum, including in subclinical stages. An important factor in understanding these variations is the subjective experience of everyday social interactions (SI). We investigated whether the presence of psychotic experiences (PEs), as well as associated distress, differs between men and women. We focused on the role of daily-life SI quality and whether its association with PEs varies by sex.

Study Design

We included adolescents from SIGMA, a general youth population study in Flanders, Belgium (n = 344; mean age = 18.7; 63.4% female). Psychotic experiences were measured using the PQ-16. We used Experience Sampling Methodology to assess daily-life SI. A multilevel model and multiple linear regressions were used to assess, respectively, the relationship between sex and SI quality and whether PEs and their association with SI quality differ between young men and women.

Study Results

The results of the multilevel linear regression model indicate that the prevalence of and distress associated with PEs were higher in women. No significant difference was observed in the subjective quality of daily SI. Social interaction quality was strongly related to PEs. This association did not seem to vary for the prevalence of PEs, though women’s distress about PEs appeared to be more affected by SI quality.

Conclusions

Present findings highlight the role of the subjective quality of SI in subclinical psychosis. More research is needed to investigate the mechanisms through which SI quality relates to PEs, and whether these differ between young men and women.
Intranasal Oxytocin Combined With Social Skills Training for Schizophrenia: An Add-on Randomized Controlled Trial
Authors: Saporta-Wiesel Liron , Feldman Ruth , Levi Linda , Davidson Michael , Burshtein Shimon , Gur Ruben , Zagoory-Sharon Orna , Amiaz Revital , Park Jinyoung , Davis John M , Weiser Mark
Published: October 2024

Some but not other studies on oxytocin for schizophrenia, particularly those using a higher dose, indicate that oxytocin improves negative symptoms of schizophrenia. We performed an add-on randomized controlled trial to examine the effect of high-dose oxytocin, social skills training, and their combination in the treatment of negative symptoms and social dysfunction in schizophrenia. Fifty-one subjects with schizophrenia were randomized, employing a two-by-two design: intranasal oxytocin (24 IU X3/day) or placebo, and social skills training or supportive psychotherapy, for 3 weeks. The primary outcome was the difference in the total score from baseline to end-of-study of a semi-structured interview which assessed patients’ social interactions in 3 scenarios: sharing a positive experience, sharing a conflict, and giving support when the experimenter shared a conflict. The interactions were scored using the Coding Interactive Behavior Manual (CIB), clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). No significant difference was found between groups in the total CIB or PANSS scores. The majority of comparisons in the different social interactions between oxytocin and placebo, and between social skills training vs supportive psychotherapy, were also nonsignificant. Social skills training reduced blunted affect and gaze. In post-hoc analyses of the support interaction, oxytocin improved synchrony and decreased tension, while in the positive interaction it improved positive affect and avoidance. None of these findings remained significant when controlling for multiple comparisons. In conclusion, oxytocin did not influence participants’ social behavior, and was not effective in improving the symptoms of schizophrenia.

Clinicaltrials.gov Identifier: NCT01598623
How openness and inquisitiveness led to a career as a sleep researcher and a broad contribution to sleep science
Authors: Roehrs Timothy
Published: October 2024

After describing my serendipitous discovery of sleep research as a potential career, I note how my openness and inquisitiveness led to a broad contribution to sleep science. After a PhD in biological psychology, I completed a postdoctoral fellowship in alcoholism and drug abuse. This led to my first studies on rebound insomnia. I then describe early studies on the relation of sleep continuity/sleep time to daytime sleepiness and function. This led to studies of how basal sleep time/sleepiness interacts with the effects of sedating and alerting drugs. Several collaborations led to studies on sleep and hot flashes in perimenopausal women and on sleep and acute and chronic pain.
Advantages of Cell Proliferation and Immune Regulation in CD146+NESTIN+ HUMSCs: Insights from Single-Cell RNA Sequencing
Authors: Huang Peng , Qin Xiaofei , Fan Chuiqin , Zhong Huifeng , Wang Manna , Chen Fuyi , Liao Maochuan , Zheng Nanpeng , Wang Hongwu , Lin Bingchun , Ma Lian
Published: October 2024

The heterogeneity of stem cells is a significant factor inhibiting their clinical application, as different cell subpopulations may exhibit substantial differences in biological functions. We performed single-cell sequencing on HUMSCs from three donors of different gestational ages (22 + 5 weeks, 28 weeks, 39 weeks). We also compared the data with single-cell sequencing data from BMSCs from two public databases. The content of CD146+Nestin+ MSCs in preterm HUMSCs (22 + 5W: 30.2%, 28W: 25.8%) was higher than that in full-term HUMSCs (39W: 0.5%) and BMSCs (BMSC1: 0, BMSC2: 0.9%). Cell cycle analysis indicated a higher proportion of cells in the proliferative G2M phase in CD146+Nestin+ MSCs (40.8%) compared to CD146+Nestin- MSCs (20%) and CD146-Nestin- MSCs (12.5%). Degree of differentiation assessment suggested that CD146+Nestin+ MSCs exhibited lower differentiation than other cell subpopulations. Differential gene analysis revealed that CD146+Nestin+ MSCs overexpressed immune regulation-related factors. GO and KEGG enrichment analysis of modules identified by WGCNA suggested enrichment in pathways related to cellular immune regulation, antimicrobial activity, and proliferation. Immune-related gene analysis indicated that CD146+Nestin+ MSCs exhibited expression of multiple immune-related genes associated with "Antimicrobials," "Cytokines," and "Cytokine Receptors." Gene regulatory network analysis revealed high expression of immune-related regulators RELB, GAPB1, and EHF in CD146+Nestin+ MSCs.Our study provides a single-cell atlas of preterm HUMSCs, demonstrating the expression of CD146+Nestin+ MSCs across different tissues and confirming their advantages in cellular proliferation, antimicrobial activity, immune regulation, and low differentiation at the RNA level. This contributes valuable insights for the clinical application of HUMSCs.
Construction of competitive endogenous RNA network and identification of potential regulatory axis in vascular calcification
Authors: Xu Tongxin , Li Yuzhe , Cheng Meijuan , Jin Jingjing , Zhang Shenglei , Bai Yaling , Xu Jinsheng
Published: October 2024

Competitive endogenous RNAs (ceRNA) theory has been proved in numerous biological processes. Nevertheless, there is a lack of research applying the ceRNA theory to the study of vascular calcification (VC) in chronic kidney diseases (CKD). In the present study, a ceRNA network was constructed after conducting transcriptome sequencing of differentially expressed genes, followed by experimental validation to identify a new target for the diagnosis and treatment of vascular calcification. Total RNA was extracted from β‐glycerophosphate (β‐GP) cultured vascular smooth muscle cells (VSMCs) on Day 7. Illumina HiSeq platform was utilized to build sequencing libraries. GO and KEGG analysis was conducted to identify the function of the differentially expressed genes. Protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. A ceRNA network was established based on TargetScan, miRDB, miRWALK, and miRanda database. Western blot and qRT‐PCR were used to explore the expression level of protein and RNA, respectively. The direct binding sites were confirmed by dual‐luciferase reporter assay. In total, 647 differentially expressed lncRNAs and 289 differentially expressed mRNAs were identified (|log2FC| ≥ 1, p < .05). The function of differentially expressed mRNAs was mainly enriched in negative regulation of osteoblast differentiation, regulation of RNA metabolic process, and other typical pathways. The ceRNA network was generated with a total of 107 interaction pairs. The lncRNA Prrc2c/miR‐145‐5p/Smad3 axis was considered a potential regulatory pathway within the ceRNA network. The regulatory relationship and targets of this ceRNA axis were validated via in vitro experiments. For the first time, we found that lncRNA Prrc2c was highly expressed and promoted calcification of VSMCs. Luciferase reporter assay showed that lncRNA Prrc2c could bind miR‐145‐5p at site 1755–1761. Similarly, luciferase reporter assay showed that miR‐145‐5p inhibited Smad3 expression by binding to its 3′UTR. Our findings provide a comprehensive examination of the ceRNA networks in vascular smooth muscle cells (VSMCs) treated with high phosphorate. Specifically, we have identified the role of lncRNA Prrc2c in promoting VSMC calcification through the miR‐145‐5p/Smad3 axis.
METTL3‐mediated m6A modification enhances lncRNA H19 stability to promote endothelial cell inflammation and pyroptosis to aggravate atherosclerosis
Authors: Tang Feng , Tian Long‐hai , Zhu Xiao‐han , Yang Sen , Zeng Huan , Yang Yong‐yao
Published: October 2024

This study explored the impact of N6‐methyladenosine (m6A) modification on the regulation of long noncoding RNA (lncRNA) and atherosclerosis progression. An atherosclerosis cell model was established by treating human aortic endothelial cells (HAECs) with oxidized low‐density lipoprotein. Additionally, an atherosclerotic animal model was developed using ApoE−/− C57BL/6 male mice fed a high‐fat diet. Both models were employed to assess the expression changes of proteins associated with m6A modification. First, the effect of m6A modification writer protein methyltransferase‐like 3 (METTL3) knockdown on changes in the level of pyroptosis in HAECs was investigated, and bioinformatic analysis confirmed that lncRNA H19 (H19) was the potential target of m6A modification. RNA‐binding protein immunoprecipitation assays were subsequently performed to explore the interaction between H19 and the m6A writer protein METTL3, as well as the reader protein recombinant insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2). Finally, the effect of H19 expression on pyroptosis levels in HAECs was evaluated. In the aortas of atherosclerosis mice, overall m6A levels were significantly elevated compared with controls (p < .05), with METTL3 and METTL14 mRNA and protein levels notably increased (p < .05). Similarly, ox‐LDL‐treated HAECs showed a significant rise in m6A levels, along with increased METTL3 and METTL14 expression (p < .05). METTL3 knockdown in HAECs led to decreased pyroptosis, as evidenced by reduced lactate dehydrogenase release and lower levels of IL‐1β, IL‐18, and IL‐6 (p < .05). Overexpression of H19 reversed these effects, indicating METTL3's role in promoting atherosclerosis by stabilizing H19 through m6A modification. H19 was the primary target lncRNA molecule of METTL3‐mediated m6A modification in the pathogenesis of atherosclerosis. METTL3‐mediated m6A modification regulated H19 expression, thereby aggravating atherosclerosis by activating pyroptosis.
Ultrasound-guided Transcutaneous Phrenic Nerve Stimulation in Critically Ill Patients: A New Method to Evaluate Diaphragmatic Function
Authors: Capdevila Mathieu , De Jong Audrey , Belafia Fouad , Vonarb Aurelie , Carr Julie , Molinari Nicolas , Choquet Olivier , Capdevila Xavier , Jaber Samir
Published: October 2024

Background:

Diaphragm dysfunction is common in intensive care unit and associated with weaning failure and mortality. The diagnosis gold standard is the transdiaphragmatic or tracheal pressure induced by magnetic phrenic nerve stimulation. However, the equipment is not commonly available and requires specific technical skills. This study aimed to evaluate ultrasound-guided transcutaneous phrenic nerve stimulation for daily bedside assessment of diaphragm function by targeted electrical phrenic nerve stimulation.

Methods:

This randomized crossover study compared a new method of ultrasound-guided transcutaneous electrical phrenic nerve stimulation (SONOTEPS) using a peripheral nerve stimulator, with magnetic phrenic nerve stimulation. Intensive care unit adult patients under mechanical ventilation with a Richmond Agitation–Sedation Scale score of −4 or −5 were included. Each patient received the two methods of stimulation, in a randomized order. The primary outcome was the tracheal pressure induced by stimulation.

Results:

This study analyzed 232 measures of tracheal pressure from 116 patients, of whom 77 presented diaphragm dysfunction (tracheal pressure less than 11 cm H2O) and 50 presented severe diaphragm dysfunction (tracheal pressure less than 8 cm H2O). The Passing–Bablok regression showed no significant differences (intercept A of −0.03 [95% CI, −0.83 to 0.52] and slope B of 0.98 [95% CI, 0.90 to 1.05]) between the SONOTEPS method and magnetic stimulation, which were positively correlated (R² = 0.639). The mean bias was −1.08 (95% CI, 5.02 to −7.18) cm H2O. The receiver operating curves showed an excellent performance for the diagnosis of diaphragm dysfunction and severe diaphragm dysfunction with areas under the curve of 0.90 (95% CI, 0.83 to 0.97) and 0.88 (95% CI, 0.82 to 0.95), respectively. This performance was not significantly affected by the body mass index or the presence of a neck catheter.

Conclusions:

The SONOTEPS method is a simple and accurate tool for bedside assessment of diaphragm function with ultrasound-guided transcutaneous phrenic nerve stimulation in sedated patients with no or minimal spontaneous respiratory activity.
Utility of Clinical Features in Identifying Electrographic Seizures in Hospitalized Patients Admitted for Non-Neurological Diagnoses
Authors: Tsai Carolyn , Blodgett Courtney , Seo Sunghyun , Alghorazi Rizk , Li Lang , Qaqish Bahjat , Powers William J. , Rubinos Clio
Published: October 2024

IMPORTANCE:

Electrographic seizures (ESz) are seizures without prominent motor activity diagnosed with electroencephalogram and are a common complication in critically ill patients with alterations of consciousness. Previous studies suggested clinical signs, including ocular movement abnormalities, facial/periorbital twitching, or remote seizure risk factors, are sensitive for presence of ESz.

OBJECTIVES:

To assess the utility of clinical features in identifying ESz in critically ill patients with alterations of consciousness.

DESIGN, SETTING, AND PARTICIPANTS:

This is a retrospective case-control study of 50 patients admitted to the University of North Carolina (UNC) Medical Center and UNC Rex Hospital. Inpatients older than 18 years old undergoing continuous video electroencephalogram (cEEG) were included. Patients admitted for neurologic diagnoses were excluded. A total of 25 patients with ESz (Sz-EEG) were matched with 25 controls by electroencephalogram duration ± 12 hours (No-Sz-EEG). Elements of patient’s history and physical findings previously shown to be sensitive for presence of ESz were collected. Descriptive statistical analyses were used.

RESULTS:

Most patients were admitted to medical ICUs (72%; n = 36). There was no difference between groups in clinical findings previously shown to be sensitive for ESz. Positive and negative likelihood ratios for these findings generally fell between 1–2 and 0.5–1, respectively, indicating they are inaccurate predictors for ESz. Patients with ESz had significantly higher mortality (p = 0.012).

CONCLUSIONS AND RELEVANCE:

Our matched case-control study showed that in the critically ill patient population hospitalized in tertiary care centers and admitted for non-neurologic primary diagnoses, incidence of ocular movement abnormalities, facial/periorbital twitching, and presence of remote risk factors for seizures had low predictive accuracy for ESz. However, these findings are not generalizable to patients with neurologic diseases or to other practice settings with different levels of access to cEEG. We concluded that in this exploratory analysis of hospitalized critically ill patients with non-neurologic diagnoses, these clinical signs did not reliably stratify risk for ESz on cEEG. However, further prospective studies are needed to better evaluate these conclusions.
Impacts of land-use and land-cover changes on temperature-related mortality
Authors: Orlov Anton , De Hertog Steven J. , Havermann Felix , Guo Suqi , Manola Iris , Lejeune Quentin , Schleussner Carl-Friedrich , Thiery Wim , Pongratz Julia , Humpenöder Florian , Popp Alexander , Aunan Kristin , Armstrong Ben , Royé Dominic , Cvijanovic Ivana , Lavigne Eric , Achilleos Souzana , Bell Michelle , Masselot Pierre , Sera Francesco , Vicedo-Cabrera Ana Maria , Gasparrini Antonio , Mistry Malcolm N. ,   Multi-Country Multi-City (MCC) Collaborative Research Network
Published: October 2024

Background:

Land-use and land-cover change (LULCC) can substantially affect climate through biogeochemical and biogeophysical effects. Here, we examine the future temperature–mortality impact for two contrasting LULCC scenarios in a background climate of low greenhouse gas concentrations. The first LULCC scenario implies a globally sustainable land use and socioeconomic development (sustainability). In the second LULCC scenario, sustainability is implemented only in the Organisation for Economic Cooperation and Development countries (inequality).

Methods:

Using the Multi-Country Multi-City (MCC) dataset on mortality from 823 locations in 52 countries and territories, we estimated the temperature–mortality exposure–response functions (ERFs). The LULCC and noLULCC scenarios were implemented in three fully coupled Earth system models (ESMs): Community Earth System Model, Max Planck Institute Earth System Model, and European Consortium Earth System Model. Next, using temperature from the ESMs’ simulations and the estimated location-specific ERFs, we assessed the temperature-related impact on mortality for the LULCC and noLULCC scenarios around the mid and end century.

Results:

Under sustainability, the multimodel mean changes in excess mortality range from −1.1 to +0.6 percentage points by 2050–2059 across all locations and from −1.4 to +0.5 percentage points by 2090–2099. Under inequality, these vary from −0.7 to +0.9 percentage points by 2050–2059 and from −1.3 to +2 percentage points by 2090–2099.

Conclusions:

While an unequal socioeconomic development and unsustainable land use could increase the burden of heat-related mortality in most regions, globally sustainable land use has the potential to reduce it in some locations. However, the total (cold and heat) impact on mortality is very location specific and strongly depends on the underlying climate change scenario due to nonlinearity in the temperature–mortality relationship.
METHA-NeP: effectiveness and safety of methadone for neuropathic pain: a controlled randomized trial
Authors: Pentiado Júnior Jorge Alberto Martins , Barbosa Marcell Maduro , Kubota Gabriel Taricani , Martins Pedro Nascimento , Moreira Larissa Iulle , Fernandes Ana Mércia , da Silva Valquíria Aparecida , Júnior Jefferson Rosi , Yeng Lin Tchia , Teixeira Manoel Jacobsen , Ciampi de Andrade Daniel
Published: October 2024

In this randomized, double-blind, parallel placebo-controlled clinical trial, we evaluated the efficacy of methadone as an add-on therapy for people with chronic neuropathic pain (NP). Eighty-six patients were randomly assigned to receive methadone or placebo for 8 weeks. The primary outcome was the proportion of participants achieving at least 30% pain relief from baseline using a 100-mm pain Visual Analogue Scale. Secondary outcomes included global impression of change, NP symptoms, sleep quality, quality of life, pain interference in daily activities, and mood. A larger number of responders were found in the methadone (68%), compared to the placebo (33%) arm; risk difference 33.6%; 95% confidence interval 13.0%-54.3%; P = 0.003; number needed to treat = 3.0. Methadone reduced pain intensity (P < 0.001), burning (P = 0.023), pressing (P = 0.005), and paroxysmal dimensions (P = 0.006) of NP. Methadone also improved sleep (P < 0.001) and increased the patient's global impression of improvement (P = 0.002). Methadone did not significantly impact quality of life, pain interference, or mood. Treatment-emergent adverse events occurred in all methadone- and in 73% of placebo-treated patients (P < 0.001). No serious adverse events or deaths occurred. Discontinuation due to adverse events was reported in 2 participants in the methadone and none in the placebo arm. Methadone use as an add-on to an optimized treatment for NP with first- and/or second-line drugs provided superior analgesia, improved sleep, and enhanced global impression of change, without being associated with significant serious adverse effects that would raise safety concerns.
Brain predicted age in chronic pelvic pain: a study by the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network
Authors: Leech Kristan A. , Kettlety Sarah A. , Mack Wendy J. , Kreder Karl J. , Schrepf Andrew , Kutch Jason J.
Published: October 2024

The effect of chronic pain on brain-predicted age is unclear. We performed secondary analyses of a large cross-sectional and 3-year longitudinal data set from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network to test the hypothesis that chronic pelvic pain accelerates brain aging and brain aging rate. Brain-predicted ages of 492 chronic pelvic pain patients and 72 controls were determined from T1-weighted MRI scans and used to calculate the brain-predicted age gap estimation (brainAGE; brain-predicted − chronological age). Separate regression models determined whether the presence of chronic pelvic pain could explain brainAGE and brain aging rate when accounting for covariates. We performed secondary analyses to understand whether brainAGE was associated with factors that subtype chronic pelvic pain patients (inflammation, widespread pain, and psychological comorbidities). We found a significant association between chronic pelvic pain and brainAGE that differed by sex. Women with chronic pelvic pain had higher brainAGE than female controls, whereas men with chronic pelvic pain exhibited lower brainAGE than male controls on average—however, the effect was not statistically significant in men or women when considered independently. Secondary analyses demonstrated preliminary evidence of an association between inflammatory load and brainAGE. Further studies of brainAGE and inflammatory load are warranted.
Harmonizing neuropathic pain research: outcomes of the London consensus meeting on peripheral tissue studies
Authors: Villa Sara , Aasvang Eske K. , Attal Nadine , Baron Ralf , Bourinet Emmanuel , Calvo Margarita , Finnerup Nanna B. , Galosi Eleonora , Hockley James R.F. , Karlsson Pall , Kemp Harriet , Körner Jannis , Kutafina Ekaterina , Lampert Angelika , Mürk Margarita , Nochi Zahra , Price Theodore J. , Rice Andrew S.C. , Sommer Claudia , Taba Pille , Themistocleous Andreas C. , Treede Rolf-Detlef , Truini Andrea , Üçeyler Nurcan , Bennett David L. , Schmid Annina B. , Denk Franziska
Published: October 2024

Neuropathic pain remains difficult to treat, with drug development hampered by an incomplete understanding of the pathogenesis of the condition, as well as a lack of biomarkers. The problem is compounded by the scarcity of relevant human peripheral tissues, including skin, nerves, and dorsal root ganglia. Efforts to obtain such samples are accelerating, increasing the need for standardisation across laboratories. In this white paper, we report on a consensus meeting attended by neuropathic pain experts, designed to accelerate protocol alignment and harmonization of studies involving relevant peripheral tissues. The meeting was held in London in March 2024 and attended by 28 networking partners, including industry and patient representatives. We achieved consensus on minimal recommended phenotyping, harmonised wet laboratory protocols, statistical design, reporting, and data sharing. Here, we also share a variety of relevant standard operating procedures as supplementary protocols. We envision that our recommendations will help unify human tissue research in the field and accelerate our understanding of how abnormal interactions between sensory neurons and their local peripheral environment contribute towards neuropathic pain.
Glial-modulating agents for the treatment of pain: a systematic review
Authors: Gilron Ian , Xiao Maggie Z. X. , Carley Meg , Salter Michael W. , Hutchinson Mark R. , Moulin Dwight E. , Moore R. Andrew , Ross-White Amanda
Published: October 2024

Preclinical research supports a critical role for nervous system glia in pain pathophysiology. This systematic review of human trials of potential glia-modulating drugs for the prevention or treatment of pain followed a predefined search strategy and protocol registration. We searched for English language, randomized, double-blind trials comparing putative glia-modulating drugs to placebo or other comparators. The primary outcomes included validated participant-reported measures of pain intensity or relief and, in studies of opioid administration, measures of opioid consumption and/or opioid-related adverse effects. Twenty-six trials (2132 participants) of glial modulators (12 minocycline, 11 pentoxifylline, and 3 ibudilast) were included. Because of clinical heterogeneity related to study drug, participant population, outcome measures, and trial design, no meta-analysis was possible. Only 6 trials reported a positive effect of the treatment (pentoxifylline—4 trials; minocycline—2 trials), whereas 11 trials reported mixed results and 9 trials reported no effect. This review does not provide convincing evidence of efficacy of current pharmacological targets of nervous system glial function for pain treatment or prevention. However, in light of ample preclinical evidence of the importance of neuroimmune signalling and glial functions in pain pathophysiology, continued strategic human research is anticipated to identify (1) drugs with maximal activity as selectively targeted glial modulators, (2) the necessary timing and duration of pharmacological glial modulation needed for pain prevention or treatment for specific injuries or pain conditions, and (3) the best design of future clinical trials of glial-targeted drugs for pain treatment and/or prevention.