bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-dimensional shear-wave velocity structure of the Adana–Iskenderun basins by ambient noise tomography
Authors: Bakırcı Taciser , Kaslilar Ayse , Kocaoğlu Argun
Published: September 2024

We construct a 3-D shear-wave velocity model for the crustal structure and the geometry of the Adana and Iskenderun basins by using ambient noise tomography of Rayleigh waves. For this purpose, we compute interstation Green's functions and measure the group velocity dispersion in the period range of 8–25 s. Then Rayleigh wave group velocity maps obtained by tomographic inversion are used to derive a shear wave velocity model by linearized inversion. Both Rayleigh wave group velocity maps and the 3-D shear-wave velocity structure are correlated with the geology and the major tectonic features of the region. Cross sections taken from the velocity model suggest a sediment thickness of up to 11 km in the wedge-shaped Adana Basin with the velocity ranging between 2.4 and 2.9 km s−1. The horseshoe-like high velocities surrounding the basin correspond to the Taurus Mountains in the west and north, and the Amanos Mountains in the east. In the region, down to a depth of 35 km the crustal velocity varies between 2.9 and 3.7 km s−1. Our investigations reveal the detailed 3-D basin geometry and crustal structure that can be beneficial for hazard assessment, geodynamic modelling as well as hydrocarbon exploration studies.
Model-based translation of results from in vitro to in vivo experiments for afabicin activity against Staphylococcus aureus
Authors: Saporta Raphaël , Nielsen Elisabet I , Menetrey Annick , Cameron David R , Nicolas-Metral Valérie , Friberg Lena E
Published: September 2024

Background

Translation of experimental data on antibiotic activity typically relies on pharmacokinetic/pharmacodynamic (PK/PD) indices. Model-based approaches, considering the full antibiotic killing time course, could be an alternative.

Objectives

To develop a mechanism-based modelling framework to assess the in vitro and in vivo activity of the FabI inhibitor antibiotic afabicin, and explore the ability of a model built on in vitro data to predict in vivo outcome.

Methods

A PK/PD model was built to describe bacterial counts from 162 static in vitro time–kill curves evaluating the effect of afabicin desphosphono, the active moiety of the prodrug afabicin, against 21 Staphylococcus aureus strains. Combined with a mouse PK model, outcomes of afabicin doses of 0.011–190 mg/kg q6h against nine S. aureus strains in a murine thigh infection model were predicted, and thereafter refined by estimating PD parameters.

Results

A sigmoid Emax model, with EC50 scaled by the MIC described the afabicin desphosphono killing in vitro. This model predicted, without parameter re-estimation, the in vivo bacterial counts at 24 h within a ±1 log margin for most dosing groups. When parameters were allowed to be estimated, EC50 was 38%–45% lower in vivo, compared with in vitro, within the studied MIC range.

Conclusions

The developed PK/PD model described the time course of afabicin activity across experimental conditions and bacterial strains. This model showed translational capacity as parameters estimated on in vitro time–kill data could well predict the in vivo outcome for a wide variety of doses in a mouse thigh infection model.
BACH to the ferroptosis
Authors: Tokunaga Fuminori
Published: September 2024

Ferroptosis is a form of regulated cell death characterized by iron-dependent phospholipid peroxidation and is closely related to various diseases. System Xc−, a cystine/glutamate antiporter, and glutathione peroxidase 4 (GPX4) are key molecules in ferroptosis. Erastin and RSL3, known as inhibitors of system Xc− and GPX4, respectively, are commonly used as ferroptosis inducers. Broad-Complex, Tramtrack and Bric a brac (BTB) and Cap‘n’collar (CNC) homology 1 (BACH1), a heme-binding transcription repressor, promotes pro-ferroptotic signalling, and therefore, Bach1-deficient cells are resistant to ferroptosis. Irikura et al. (Ferroptosis model system by the re-expression of BACH1. J. Biochem. 2023;174:239–52) constructed Bach1-re-expressing immortalized mouse embryonic fibroblasts (iMEFs) from Bach1−/− mice, which induce ferroptosis simply through the depletion of 2-mercaptoethanol from the culture medium. Transcriptional repression by re-expressed BACH1 induces suppressed glutathione synthesis and increases labile iron. Furthermore, ferroptosis initiated by BACH1-re-expressing iMEFs is propagated to surrounding cells. Thus, the BACH1-re-expression system is a novel and powerful tool to investigate the cellular basis of ferroptosis.
Pastor Nevers Mumba’s Quest to Actualize the Declaration of Zambia as a Christian Nation through “Zambia Shall Be Saved” Campaign, 1993–2021
Authors: Cheyeka Austin Mumba
Published: September 2024

This article is grounded in the findings from qualitative and interpretivist research based on secondary and primary data. Two analytic frameworks have been used to make sense of the data. The first is Stephen Ellis and Gerrie ter Haar’s hypothesis that politics in sub-Saharan African societies cannot be fully understood without reference to religious ideas therein; and the second is the notion of African Political Theology which, according to Emmanuel Katongole, means going beyond addressing realities of violence, civil unrest, poverty, tribalism, and corruption, but deploying the story of salvation in Jesus as a concrete social, material, political, and economic reality in the African social imaginary for the construction of modern Africa. The article argues that through “Zambia Shall be Saved” orations from 1993 to date, Pastor Nevers Mumba has been calling for actualizing the declaration of Zambia as a Christian Nation (henceforth referred to as “Declaration”) made by President Frederick Chiluba in 1991. Katongole’s understanding of African Political Theology provides an invaluable lens for conceptualizing Mumba’s “Zambia Shall be Saved” discourse. The Declaration remains a topical issue among Zambian and international analysts and the significance of this particular article lies in the fact that it relates Mumba’s cry of “Zambia Shall be Saved” to the new conversation on “Actualizing the Declaration” coined by the government of the republic of Zambia in 2016. Overall, the article seeks to contribute to an ongoing discourse on Zambia’s Christian nationhood.
Impact of COVID-19 on 2021 cancer incidence rates and potential rebound from 2020 decline
Authors: Howlader Nadia , Chen Huann-Sheng , Noone Anne-Michelle , Miller Daniel , Byrne Jeffry , Negoita Serban , Cronin Kathleen A , Mariotto Angela B
Published: September 2024

The COVID-19 pandemic led to substantial declines in cancer incidence rates in 2020, likely because of disruptions in screening and diagnostic services. This study aimed to assess the impact of the pandemic on cancer incidence rates in the United States using 2021 incidence data from the Surveillance, Epidemiology, and End Results program. The analysis compared observed 2021 cancer incidence rates with expected prepandemic trends, evaluating changes by individual cancer site and stage. Although incidence overall and in many cancer sites the rates were close to prepandemic levels, they did not exhibit a recovery that incorporated the delayed diagnoses from 2020. There were exceptions, however, such as metastatic breast cancer, which showed significantly higher observed rates than expected (rate ratio = 1.09, 95% confidence interval = 1.04 to 1.13). Ongoing monitoring and targeted interventions are needed to address the long-term consequences of the COVID-19 pandemic on cancer care and outcomes.
A comparison of some existing and novel methods for integrating historical models to improve estimation of coefficients in logistic regression
Authors: Boonstra Philip S , Orozco del Pino Pedro
Published: September 2024

Model integration refers to the process of incorporating a fitted historical model into the estimation of a current study to increase statistical efficiency. Integration can be challenging when the current model includes new covariates, leading to potential model misspecification. We present and evaluate seven existing and novel model integration techniques, which employ both likelihood constraints and Bayesian informative priors. Using a simulation study of logistic regression, we quantify how efficiency—assessed by bias and variance—changes with the sample sizes of both historical and current studies and in response to violations to transportability assumptions. We also apply these methods to a case study in which the goal is to use novel predictors to update a risk prediction model for in-hospital mortality among pediatric extracorporeal membrane oxygenation patients. Our simulation study and case study suggest that (i) when historical sample size is small, accounting for this statistical uncertainty is more efficient; (ii) all methods lose efficiency when there exist differences between the historical and current data-generating mechanisms; (iii) additional shrinkage to zero can improve efficiency in higher-dimensional settings but at the cost of bias in estimation.
Βελό́στασις in LXX Jeremiah 28:27 (51:27): A Conjectural Emendation
Authors: Keenan Andrew T
Published: September 2024

In LXX Jer. 28:27 (51:27) there is a semantic mismatch between the Greek βελόστασις, an ‘emplacement for the discharge of missiles’, and the Hebrew טִפְסָר, a ‘tablet writer’. Rather than viewing this reading as a mistake made by the translator, alternative solutions will be suggested. A consideration of several additional factors recommends a conjectural emendation. It will be proposed that the conjectural emendation may resolve the semantic discrepancy between the LXX Jer. 28:27 and the MT.
The Association of Calcium Derangements With 24-Hour Outcomes in the Deployed Combat Setting
Authors: Nguyen Matthew M , Givens Melissa L , Fisher Andrew D , Rizzo Julie A , Ditzel Ricky M , Braverman Maxwell A , April Michael D , Schauer Steven G
Published: September 2024

Introduction

Calcium derangements remain poorly characterized in the combat trauma population. We describe the incidence of emergency department (ED) calcium derangements, associated physiologic derangements, and 24-hour mortality from the deployed combat setting.

Materials and Methods

We analyzed adult casualties from 2007 to 2023 from the DoD Trauma Registry for U.S. military, U.S. contractor, and coalition casualties that had at least 1 ionized calcium value documented in the ED at a Role 2 or Role 3 military treatment facility. We constructed a series of multivariable logistic regression models to test for the association of hypocalcemia and hypercalcemia with physiological derangements, blood product consumption, and survival. Vital signs and other laboratory studies were based on the concurrent ED encounter.

Results

There were 941 casualties that met inclusion for this analysis with 26% (245) having at least 1 calcium derangement. Among those, 22% (211) had at least 1 episode of hypocalcemia and 5% (43) had at least 1 episode of hypercalcemia in the ED. The vast majority (97%, 917) received calcium at least once. Median composite injury severity scores were lower among those with no calcium derangement (8 versus 17, P < .001). Survival was higher during the total hospitalization (98% versus 93%) among those with calcium derangements but similar at 24 hours (99% versus 98%, P = .059). After adjusting for confounder, any hypocalcemic measurement was associated with an elevated international normalized ratio (odds ratio 1.94, 95% CI 1.19–3.16), acidosis (1.66, 1.17–2.37), tachycardia (2.11, 1.42–3.15), hypotension (1.92, 1.09–3.38), depressed Glasgow coma scale (3.20, 2.13–4.81), elevated shock index (2.19, 1.45–3.31), submassive transfusion (3.97, 2.60–6.05), massive transfusion (4.22, 2.66–6.70), supermassive transfusion (3.65, 2.07–6.43), and all hospital stay mortality (2.30, 1.00–5.29). Comparatively, any hypercalcemic measurement was associated with acidosis (2.96, 1.39–6.32), depressed Glasgow coma scale (4.28, 1.81–10.13), submassive transfusion (3.40, 1.37–8.43), massive transfusion (6.25, 2.63–14.83), and supermassive transfusion (13.00, 5.47–30.85).

Conclusions

Both hypocalcemia and hypercalcemia in the ED were associated with physiological derangements and blood product use, with a greater extent observed in those with hypocalcemia compared to those with hypercalcemia. Prospective studies are underway to better explain and validate these findings.
Family Physician Education and Barriers to Promoting Smoking Cessation: A Multiservice Investigation
Authors: Domalaon Kryls , Valerio Christina
Published: September 2024

Introduction

Cigarette smoking remains the leading cause of preventable disease and death in the United States. Brief discussions with doctors increase cessation rates by two-thirds, and physicians trained in smoking cessation are more likely to perform counseling. Multiple organizations also recommend connecting counseling with lung cancer screening (LCS), yet physicians and patients report a lack of such integration. We sought to characterize the education received and the barriers to providing smoking cessation counseling, and to determine its integration with LCS among military Family Medicine physicians.

Methods

This is a cross-sectional study of registered attendees of 2022 Uniformed Services Academy of Family Physicians Annual Conference. Our study aimed to: (1) Assess the amount of formal smoking cessation education during and after residency; (2) assess barriers to providing smoking cessation within the military health care system; and (3) assess if physicians connect smoking cessation counseling and LCS. Descriptive statistics with chi-squared analysis were used to analyze the survey results.

Results

With a response rate of 61% (n = 323/487), most participants reported receiving <3 sessions of formal education during residency (72.9%) and <3 h after residency (76.2%). Forty-eight percent cited their health care system never or rarely provided resources on smoking cessation. Time was the largest barrier to promoting smoking cessation (62.6%) and to integrating it with LCS (56.7%), although a considerable percentage also cited lack of supporting staff (34.3%). Furthermore, only 50.6% of respondents always reported counseling on smoking cessation with LCS.

Conclusion

Smoking cessation education is provided in family medicine residencies but rarely offered afterwards. Time and lack of support staff and resources are recognized as notable barriers within the military health care system. A large proportion of uniformed Family Medicine physicians also do not link LCS guidelines with patient education on tobacco cessation and resources. Further research is needed to guide interventions to overcome these challenges within the military health care system.
[Ne v] emission from a faint epoch of reionization-era galaxy: evidence for a narrow-line intermediate-mass black hole
Authors: Chisholm J , Berg D A , Endsley R , Gazagnes S , Richardson C T , Lambrides E , Greene J , Finkelstein S , Flury S , Guseva N G , Henry A , Hutchison T A , Izotov Y I , Marques-Chaves R , Oesch P , Papovich C , Saldana-Lopez A , Schaerer D , Stephenson M  G
Published: September 2024

Here, we present high spectral resolution ${\it JWST}$ NIRSpec observations of GN 42437, a low-mass (log(M$_\ast /{\rm M}_\odot)=7.9$), compact ($r_e \lt 500$pc), extreme starburst galaxy at $z=5.59$ with 13 emission-line detections. GN 42437 has a low metallicity (5–10 per cent Z$_\odot$) and its rest-frame H$\alpha$ equivalent width suggests nearly all of the observed stellar mass formed within the last 3 Myr. GN 42437 has an extraordinary 7$\sigma$ significant [Ne v] 3427 Å detection. The [Ne v] line has a rest-frame equivalent width of $11\pm 2$Å, [Ne v]/H$\alpha =0.04\pm 0.007$, [Ne v]/[Ne iii] 3870Å $= 0.26\pm 0.04$, and [Ne v]/He ii 4687Å $ = 1.2\pm 0.5$. Ionization from massive stars, shocks, or high-mass X-ray binaries cannot simultaneously produce these [Ne v] and other low-ionization line ratios. Reproducing the complete nebular structure requires both massive stars and accretion on to a black hole. We do not detect broad lines nor do the traditional diagnostics indicate that GN 42437 has an accreting black hole. Thus, the very high-ionization emission lines powerfully diagnose faint narrow-line black holes at high redshift. We approximate the black hole mass in a variety of ways as log(M$_{\rm BH}/{\rm M}_\odot) \sim 5{-}7$. This black hole mass is consistent with local relations between the black hole mass and the observed velocity dispersion, but significantly more massive than the stellar mass would predict. Very high-ionization emission lines may reveal samples to probe the formation and growth of the first black holes in the universe.
Hierarchical three-body problem at high eccentricities = simple pendulum II: octupole including Brown’s Hamiltonian
Authors: Klein Ygal Y , Katz Boaz
Published: September 2024

The very long-term evolution of the hierarchical restricted three-body problem with a massive perturber is analysed analytically in the high eccentricity regime. Perturbations on the time-scale of the outer orbit can accumulate over long time-scales and be comparable to the effect of the octupole term. These perturbations are described by Brown’s Hamiltonian – having different forms in the literature. We show that at the high eccentricity regime – the effect of Brown’s Hamiltonian is an azimuthal precession of the eccentricity vector and can be solved analytically. In fact, the dynamics are equivalent to a simple pendulum model allowing an explicit flip criterion.
Chem-CRISPR/dCas9FCPF: a platform for chemically induced epigenome editing
Authors: Altinbay Mukaddes , Wang Jianhui , Chen Jie , Schäfer Daniel , Sprang Maximilian , Blagojevic Biljana , Wölfl Stefan , Andrade-Navarro Miguel A , Dikic Ivan , Knapp Stefan , Cheng Xinlai
Published: September 2024

Epigenetic aberration is one of the major driving factors in human cancer, often leading to acquired resistance to chemotherapies. Various small molecule epigenetic modulators have been reported. Nonetheless, outcomes from animal models and clinical trials have underscored the substantial setbacks attributed to pronounced on- and off-target toxicities. To address these challenges, CRISPR/dCas9 technology is emerging as a potent tool for precise modulation of epigenetic mechanism. However, this technology involves co-expressing exogenous epigenetic modulator proteins, which presents technical challenges in preparation and delivery with potential undesirable side effects. Recently, our research demonstrated that Cas9 tagged with the Phe-Cys-Pro-Phe (FCPF)-peptide motif can be specifically targeted by perfluorobiphenyl (PFB) derivatives. Here, we integrated the FCPF-tag into dCas9 and established a chemically inducible platform for epigenome editing, called Chem-CRISPR/dCas9FCPF. We designed a series of chemical inhibitor-PFB conjugates targeting various epigenetic modulator proteins. Focusing on JQ1, a panBET inhibitor, we demonstrate that c-MYC-sgRNA-guided JQ1-PFB specifically inhibits BRD4 in close proximity to the c-MYC promoter/enhancer, thereby effectively repressing the intricate transcription networks orchestrated by c-MYC as compared with JQ1 alone. In conclusion, our Chem-CRISPR/dCas9FCPF platform significantly increased target specificity of chemical epigenetic inhibitors, offering a viable alternative to conventional fusion protein systems for epigenome editing.
FRAME: flap endonuclease 1-engineered PAM module for precise and sensitive modulation of CRISPR/Cas12a trans-cleavage activity
Authors: Zuo Tongshan , Shen Chen , Xie Zhen , Xu Guanhong , Wei Fangdi , Yang Jing , Zhu Xiaolei , Hu Qin , Zhao Zheng , Tang Ben Zhong , Cen Yao
Published: September 2024

CRISPR/Cas12a system, renowned for its precise recognition and efficient nucleic acid cleavage capabilities, has demonstrated remarkable performance in molecular diagnostics and biosensing. However, the reported Cas12a activity regulation methods often involved intricate CRISPR RNA (crRNA) structural adjustments or costly chemical modifications, which limited their applications. Here, we demonstrated a unique enzyme activity engineering strategy using flap endonuclease 1 (FEN1) to regulate the accessibility of the protospacer adjacent motif (PAM) module in the double-stranded DNA activator (FRAME). By identifying the three-base overlapping structure between the target inputs and substrate, FEN1 selectively cleaved and released the 5′-flap containing the ‘TTTN’ sequence, which triggered the secondary cleavage of FEN1 while forming a nicked PAM, ultimately achieving the sensitive switching of Cas12a’s activity. The FRAME strategy exemplified the ‘two birds with one stone’ principle, as it not only precisely programmed Cas12a’s activity but also simultaneously triggered isothermal cyclic amplification. Moreover, the FRAME strategy was applied to construct a sensing platform for detecting myeloperoxidase and miR-155, which demonstrated high sensitivity and specificity. Importantly, it proved its versatility in detecting multiple targets using a single crRNA without redesign. Collectively, the FRAME strategy opens up a novel avenue for modulating Cas12a’s activity, promising immense potential in the realm of medical diagnostics.
p53-dependent crosstalk between DNA replication integrity and redox metabolism mediated through a NRF2-PARP1 axis
Authors: Elfar Gamal Ahmed , Aning Obed , Ngai Tsz Wai , Yeo Pearlyn , Chan Joel Wai Kit , Sim Shang Hong , Goh Leonard , Yuan Ju , Phua Cheryl Zi Jin , Yeo Joanna Zhen Zhen , Mak Shi Ya , Goh Brian Kim Poh , Chow Pierce Kah-Hoe , Tam Wai Leong , Ho Ying Swan , Cheok Chit Fang
Published: September 2024

Mechanisms underlying p53-mediated protection of the replicating genome remain elusive, despite the quintessential role of p53 in maintaining genomic stability. Here, we uncover an unexpected function of p53 in curbing replication stress by limiting PARP1 activity and preventing the unscheduled degradation of deprotected stalled forks. We searched for p53-dependent factors and elucidated RRM2B as a prime factor. Deficiency in p53/RRM2B results in the activation of an NRF2 antioxidant transcriptional program, with a concomitant elevation in basal PARylation in cells. Dissecting the consequences of p53/RRM2B loss revealed a crosstalk between redox metabolism and genome integrity that is negotiated through a hitherto undescribed NRF2-PARP1 axis, and pinpoint G6PD as a primary oxidative stress-induced NRF2 target and activator of basal PARylation. This study elucidates how loss of p53 could be destabilizing for the replicating genome and, importantly, describes an unanticipated crosstalk between redox metabolism, PARP1 and p53 tumor suppressor pathway that is broadly relevant in cancers and can be leveraged therapeutically.
Phage defence loci of Streptococcus thermophilus—tip of the anti-phage iceberg?
Authors: Kelleher Philip , Ortiz Charneco Guillermo , Kampff Zoe , Diaz-Garrido Natalia , Bottacini Francesca , McDonnell Brian , Lugli Gabriele A , Ventura Marco , Fomenkov Alexey , Quénée Pascal , Kulakauskas Saulius , de Waal Paul , van Peij Noël N M E , Cambillau Christian , Roberts Richard John , van Sinderen Douwe , Mahony Jennifer
Published: September 2024

Bacteria possess (bacterio)phage defence systems to ensure their survival. The thermophilic lactic acid bacterium, Streptococcus thermophilus, which is used in dairy fermentations, harbours multiple CRISPR-Cas and restriction and modification (R/M) systems to protect itself against phage attack, with limited reports on other types of phage-resistance. Here, we describe the systematic identification and functional analysis of the phage resistome of S. thermophilus using a collection of 27 strains as representatives of the species. In addition to CRISPR-Cas and R/M systems, we uncover nine distinct phage-resistance systems including homologues of Kiwa, Gabija, Dodola, defence-associated sirtuins and classical lactococcal/streptococcal abortive infection systems. The genes encoding several of these newly identified S. thermophilus antiphage systems are located in proximity to the genetic determinants of CRISPR-Cas systems thus constituting apparent Phage Defence Islands. Other phage-resistance systems whose encoding genes are not co-located with genes specifying CRISPR-Cas systems may represent anchors to identify additional Defence Islands harbouring, as yet, uncharacterised phage defence systems. We estimate that up to 2.5% of the genetic material of the analysed strains is dedicated to phage defence, highlighting that phage-host antagonism plays an important role in driving the evolution and shaping the composition of dairy streptococcal genomes.
3,N4-Etheno-5-methylcytosine blocks TET1-3 oxidation but is repaired by ALKBH2, 3 and FTO
Authors: Ma Jian , Qi Rui , Harcourt Emily M , Chen Yi-Tzai , Barbosa Giovannia M , Peng Zhiyuan , Howarth Samuel , Delaney Sarah , Li Deyu
Published: September 2024

5-Methyldeoxycytidine (5mC) is a major epigenetic marker that regulates cellular functions in mammals. Endogenous lipid peroxidation can convert 5mC into 3,N4-etheno-5-methylcytosine (ϵ5mC). ϵ5mC is structurally similar to the mutagenic analog 3,N4-ethenocytosine (ϵC), which is repaired by AlkB family enzymes in the direct reversal repair (DRR) pathway and excised by DNA glycosylases in the base excision repair (BER) pathway. However, the repair of ϵ5mC has not been reported. Here, we examined the activities against ϵ5mC by DRR and BER enzymes and TET1-3, enzymes that modify the 5-methyl group in 5mC. We found that the etheno modification of 5mC blocks oxidation by TET1-3. Conversely, three human homologs in the AlkB family, ALKBH2, 3 and FTO were able to repair ϵ5mC to 5mC, which was subsequently modified by TET1 to 5-hydroxymethylcytosine. We also demonstrated that ALKBH2 likely repairs ϵ5mC in MEF cells. Another homolog, ALKBH5, could not repair ϵ5mC. Also, ϵ5mC is not a substrate for BER glycosylases SMUG1, AAG, or TDG. These findings indicate DRR committed by ALKBH2, 3 and FTO could reduce the detrimental effects of ϵ5mC in genetics and epigenetics and may work together with TET enzymes to modulate epigenetic regulations.
scMMO-atlas: a single cell multimodal omics atlas and portal for exploring fine cell heterogeneity and cell dynamics
Authors: Cheng Wenwen , Yin Changhui , Yu Shiya , Chen Xi , Hong Ni , Jin Wenfei
Published: September 2024

Single-cell multimodal sequencing parallelly captures multiple modalities of the same cell, providing unparalleled insights into cell heterogeneity and cell dynamics. For example, joint profiling of chromatin accessibility and transcriptome from the same single cell (scATAC + RNA) identified new cell subsets within the well-defined clusters. However, lack of single-cell multimodal omics (scMMO) database has led to data fragmentation, seriously hindering access, utilization and mining of scMMO data. Here, we constructed a scMMO atlas by collecting and integrating various scMMO data, then constructed scMMO database and portal called scMMO-atlas (https://www.biosino.org/scMMO-atlas/). scMMO-atlas includes scATAC + RNA (ISSAAS-seq, SNARE-seq, paired-seq, sci-CAR, scCARE-seq, 10X Multiome and so on), scRNA + protein, scATAC + protein and scTri-modal omics data, with 3 168 824 cells from 27 cell tissues/organs. scMMO-atlas offered an interactive portal for visualization and featured analysis for each modality and the integrated data. Integrated analysis of scATAC + RNA data of mouse cerebral cortex in scMMO-atlas identified more cell subsets compared with unimodal omics data. Among these new cell subsets, there is an early astrocyte subset highly expressed Grm3, called Astro-Grm3. Furthermore, we identified Ex-L6-Tle4-Nrf1, a progenitor of Ex-L6-Tle4, indicating the statistical power provided by the big data in scMMO-atlas. In summary, scMMO-atlas offers cell atlas, database and portal to facilitate data utilization and biological insight.
Disparate requirements for RAD54L in replication fork reversal
Authors: Uhrig Mollie E , Sharma Neelam , Maxwell Petey , Gomez Jordi , Selemenakis Platon , Mazin Alexander V , Wiese Claudia
Published: September 2024

RAD54L is a DNA motor protein with multiple roles in homologous recombination DNA repair. In vitro, RAD54L was shown to also catalyze the reversal and restoration of model replication forks. In cells, however, little is known about how RAD54L may regulate the dynamics of DNA replication. Here, we show that RAD54L restrains the progression of replication forks and functions as a fork remodeler in human cancer cell lines and non-transformed cells. Analogous to HLTF, SMARCAL1 and FBH1, and consistent with a role in fork reversal, RAD54L decelerates fork progression in response to replication stress and suppresses the formation of replication-associated ssDNA gaps. Interestingly, loss of RAD54L prevents nascent strand DNA degradation in both BRCA1/2- and 53BP1-deficient cells, suggesting that RAD54L functions in both pathways of RAD51-mediated replication fork reversal. In the HLTF/SMARCAL1 pathway, RAD54L is critical, but its ability to catalyze branch migration is dispensable, indicative of its function downstream of HLTF/SMARCAL1. Conversely, in the FBH1 pathway, branch migration activity of RAD54L is essential, and FBH1 engagement is dependent on its concerted action with RAD54L. Collectively, our results reveal disparate requirements for RAD54L in two distinct RAD51-mediated fork reversal pathways, positing its potential as a future therapeutic target.
Severe Optic Neuropathy Induced by Very Prolonged Tedizolid as Suppressive Therapy: Description of a Case Report and Implication for Better Assessment
Authors: Coustilleres F , Thillard E M , Khanna R K , Olivereau S , Ouaissi M , Pansu N , Le Lez M L
Published: September 2024

The long-term tolerability of linezolid is low because of mitochondrial toxicity, whereas tedizolid may represent a better option for suppressive therapy. We report a first presumed case of tedizolid-associated optic neuropathy after a very prolonged (18-month) intake and believe that screening for optic neuropathy should be considered for patients undergoing tedizolid suppression.
The ubiquitin E3 ligase RZFP1 affects drought tolerance in poplar by mediating the degradation of the protein phosphatase PP2C-9
Authors: He Fang , Niu Meng-Xue , Wang Ting , Li Jun-Lin , Shi Yu-Jie , Zhao Jiu-Jiu , Li Hao , Xiang Xiang , Yang Peng , Wei Shu-Ying , Lin Tian-Tian , Huang Xiong , Xia Xinli , Wan Xue-Qin
Published: September 2024

Abscisic acid (ABA) signaling has been implicated in plant responses to water deficit-induced osmotic stress. However, the underlying molecular mechanism remains unelucidated. This study identified the RING-type E3 ubiquitin ligase RING ZINC FINGER PROTEIN1 (PtrRZFP1) in poplar (Populus trichocarpa), a woody model plant. PtrRZFP1 encodes an ubiquitin E3 ligase that participates in protein ubiquitination. PtrRZFP1 mainly functions in the nucleus and endoplasmic reticulum and is activated by drought and ABA. PtrRZFP1-overexpressing transgenic poplars (35S:PtrRZFP1) showed greater tolerance to drought, whereas PtrRZFP1-knockdown lines (KD-PtrRZFP1) showed greater sensitivity to drought. Under treatment with polyethylene glycol and ABA, PtrRZFP1 promoted the production of nitric oxide and hydrogen peroxide in stomatal guard cells, ultimately enhancing stomatal closure and improving drought tolerance. Additionally, PtrRZFP1 physically interacted with the clade A Protein Phosphatase 2C protein PtrPP2C-9, a core regulator of ABA signaling, and mediated its ubiquitination and eventual degradation through the ubiquitination-26S proteasome system, indicating that PtrRZFP1 positively regulates the ABA signaling pathway. Furthermore, the PtrPP2C-9-overexpression line was insensitive to ABA and more sensitive to drought than the wild-type plants, whereas the opposite phenotype was observed in 35S:PtrRZFP1 plants. In general, PtrRZFP1 negatively regulates the stability of PtrPP2C-9 to mediate poplar drought tolerance. The results of this study provide a theoretical framework for the targeted breeding of drought-tolerant traits in perennial woody plants.
Every History
Authors: Knutzen Jonathan
Published: September 2024

This paper focuses on an underexplored challenge in infinite ethics. On realistic assumptions, if our universe is infinite, every nomologically possible history is actual and nothing we ever do makes a difference to the moral quality of the world as a whole. Call this thought Every History. This paper unpacks Every History and explores some of its ethical implications. Specifically, I argue that if Every History is true and the universe turns out to be infinite (1) our lives are globally insignificant, (2) moral principles enjoining the promotion of value need to be given an appropriately scope-restricted interpretation, and (3) impersonal consequentialism faces a serious challenge.
Emotional unreliability and epistemic defeat
Authors: Magalotti Tricia
Published: September 2024

Among those who think that emotions can provide epistemic reasons for belief, there is disagreement about whether emotions provide foundational reasons (ones that are not based on further reasons) or non-foundational reasons (ones that are based on further reasons). I argue in this paper that considerations about evidence of emotional unreliability favour the non-foundational view of emotional reasons. The argument starts with a set of counterexamples to the claim that evidence of emotional unreliability always defeats emotional justification. I then show why only the non-foundational picture of emotional reasons is compatible with this finding. The upshot is 2-fold: first, the commonly held assumption that evidence of emotional unreliability always defeats emotional justification is false; and, second, this gives us a reason for preferring a non-foundational picture of emotional reasons.
Capital Investment, Equity Returns, and Aggregate Dynamics in Oligopolistic Production Economies
Authors: Doshi Hitesh , Kumar Praveen
Published: September 2024

We analyze effects of tacit collusion in a dynamic general equilibrium model of oligopolistic sectors with capital investment and real frictions. Through their effects on equilibrium- and off-equilibrium stock prices, fundamental shocks affect incentives for defection from tacit collusion, amplifying the interaction between the real economy and financial markets as well as firms’ risk exposure. The model implies ambiguous relationship between industry concentration and equity returns depending on operating leverage, which helps reconcile conflicting evidence in the literature. We find quantitative and empirical support for novel theoretical predictions regarding the effects of concentration on returns and investment.
Electrochemical impedance spectroscopy unmasks high‐risk atherosclerotic features in human coronary artery disease
Authors: Chen Michael , Suwannaphoom Krit , Sanaiha Yas , Luo Yuan , Benharash Peyman , Fishbein Michael C. , Packard René R. Sevag
Published: September 2024

Coronary plaque rupture remains the prominent mechanism of myocardial infarction. Accurate identification of rupture‐prone plaque may improve clinical management. This study assessed the discriminatory performance of electrochemical impedance spectroscopy (EIS) in human cardiac explants to detect high‐risk atherosclerotic features that portend rupture risk. In this single‐center, prospective study, n = 26 cardiac explants were collected for EIS interrogation of the three major coronary arteries. Vessels in which advancement of the EIS catheter without iatrogenic plaque disruption was rendered impossible were not assessed. N = 61 vessels underwent EIS measurement and histological analyses. Plaques were dichotomized according to previously established high rupture‐risk parameter thresholds. Diagnostic performance was determined via receiver operating characteristic areas‐under‐the‐curve (AUC). Necrotic cores were identified in n = 19 vessels (median area 1.53 mm2) with a median fibrous cap thickness of 62 μm. Impedance was significantly greater in plaques with necrotic core area ≥1.75 mm2 versus <1.75 mm2 (19.8 ± 4.4 kΩ vs. 7.2 ± 1.0 kΩ, p = .019), fibrous cap thickness ≤65 μm versus >65 μm (19.1 ± 3.5 kΩ vs. 6.5 ± 0.9 kΩ, p = .004), and ≥20 macrophages per 0.3 mm‐diameter high‐power field (HPF) versus <20 macrophages per HPF (19.8 ± 4.1 kΩ vs. 10.2 ± 0.9 kΩ, p = .002). Impedance identified necrotic core area ≥1.75 mm2, fibrous cap thickness ≤65 μm, and ≥20 macrophages per HPF with AUCs of 0.889 (95% CI: 0.716–1.000) (p = .013), 0.852 (0.646–1.000) (p = .025), and 0.835 (0.577–1.000) (p = .028), respectively. Further, phase delay discriminated severe stenosis (≥70%) with an AUC of 0.767 (0.573–0.962) (p = .035). EIS discriminates high‐risk atherosclerotic features that portend plaque rupture in human coronary artery disease and may serve as a complementary modality for angiography‐guided atherosclerosis evaluation.
Celiac disease
Authors: Olmstead Jill
Published: September 2024

The American College of Gastroenterology revised its recommendations for diagnosing and managing celiac disease in its updated 2023 clinical guideline. Celiac disease is an autoimmune disorder causing malabsorption following exposure to gluten. A wide range of both gastrointestinal and nongastrointestinal signs and symptoms can occur. This article provides an overview of the diagnosis and management of celiac disease, aiding the NP in developing a greater awareness of the condition both to diagnose it and to refer patients as needed to gastroenterology for evaluation.
Relative Perioperative Analgesic Efficacy of Superficial Versus Deep Approach of Serratus Anterior Plane Block for Anterior Chest Wall Surgery
Authors: Singh Narinder P. , Makkar Jeetinder Kaur , Dhawan Ira , Singh Neha , Singh Preet M. , Siddiqui Naveed
Published: September 2024

Objectives:

Both superficial and deep serratus anterior plane (SAP) blocks are effective for anterior chest wall surgeries, but there is little clarity on which is more effective. Hence, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the comparative efficacy of the 2 approaches for SAP block after anterior chest wall surgery.

Materials and Methods:

A systematic literature search was performed using PubMed, Embase, Scopus, and Cochrane Central Registers of Controlled Trials for eligible RCTs from inception until August 2023. The primary outcome was opioid consumption during the first 24 hours of the postoperative period. The secondary outcomes included pain scores at various intervals, intraoperative opioid consumption, time to first analgesic request, block-related complications, opioid-related side effects, and patient satisfaction scores. Statistical analysis of the pooled data was performed using Review Manager Version 5.3.

Results:

We identified 7 RCTs published between 2020 and 2022, enrolling 371 patients (186 in the superficial SAP block and 187 in the deep SAP block). Moderate certainty of evidence suggests that both the approaches (deep and superficial) of SAP block were comparable for 24-hour oral morphine equivalent consumption with a mean difference (MD) of 3.78 mg (95% CI: −1.70 to 9.29; P = 0.18; I
2 = 87%). The results of other secondary outcomes were comparable, including resting pain scores with an MD of 0.08 (95% CI: −0.27 to 0.43; P = 0.67; I
2 = 87%) for early pain and MD of 0.63 (95% CI: −1.28 to 0.01; P = 0.05; I
2 = 95%) for late pain scores, time to first analgesic request with MD of −0.41 hour (95% CI: −1.40 to 0.59; P = 0.42; I
2 = 90%), and incidence of postoperative nausea and vomiting (odds ratio: 1.45 (95% CI: 0.72 to 2.90; P = 0.30; I
2 = 0%).

Conclusion:

Current evidence does not support the preference for one approach of SAP block over the other for postoperative pain. Based on the available data, we recommend further future trials to determine any differences between these interventions.
INCIDENCE OF STEROID-RELATED OCULAR HYPERTENSION AND CATARACT FORMATION AFTER SUB-TENON TRIAMCINOLONE IN NONUVEITIC PEDIATRIC PATIENTS
Authors: Patel Nimesh A. , Hoyek Sandra , López-Font Francisco J. , Shah Serena , Ha Sierra , da Cruz Natasha F. S. , Vu Daniel M. , Chang Ta Chen , Berrocal Audina M.
Published: September 2024

Purpose:

To describe intraocular pressure changes after injection of sub-Tenon triamcinolone during examination under anesthesia for pediatric patients.

Methods:

Multicenter, retrospective case series of pediatric patients who received sub-Tenon triamcinolone from three tertiary care ophthalmic services between November 2018 and October 2023.

Results:

Of 392 patients identified, 59 eyes (10.5%) of 41 patients were included. Laser was administered in 95.1% of the cases. Sub-Tenon triamcinolone dose ranged from 4 to 20 mg. The most common diagnosis was retinopathy of prematurity (43.9%). Two eyes (3.4%) of two patients (4.9%) were mild steroid responders. One eye (1.7%) of 1 patient (2.4%) was a moderate responder. There were no high steroid responders, and all eyes with steroid response showed a return of intraocular pressure to normal range at next visit without needing any intraocular pressure-lowering medications. No patients were diagnosed with glaucoma or required glaucoma surgery. Only 1 eye (1.7%) developed trace posterior subcapsular cataract, whereas no optic disk cupping or inflammation were noted.

Conclusion:

Sub-Tenon triamcinolone injection is commonly used to prevent inflammation at the time of retinal photocoagulation treatment in pediatric patients. It has a favorable safety profile in relation to intraocular pressure elevation and cataract formation. There was no requirement for intraocular pressure–lowering medications or surgical interventions.
Medical Adhesive-Related Skin Injury at 10 Years
Authors: Barton Andrew , Broadhurst Daphne , Hitchcock Jan , Lund Carolyn , McNichol Laurie , Ratliff Catherine R. , Moraes Juliano Teixeira , Yates Stephanie , Gray Mikel
Published: September 2024

Awareness of medical adhesive-related skin injury (MARSI) has increased in the decade since a foundational consensus report was published in 2013. Additional research has provided greater knowledge of the epidemiology of MARSI, along with its assessment, prevention, and management. To summarize knowledge generated in the past decade and review our current understanding of MARSI, a panel of nine clinical experts from four countries (United States of America, United Kingdom, Canada, and Brazil) convened to discuss the literature published since the initial 2013 document and develop updated recommendations for clinical practice. The group formulated 20 updated consensus statements covering the assessment, prevention, and management of skin injuries related to adhesive medical devices and proposed next steps to address remaining gaps in research and knowledge of this complex and clinically relevant condition.
Accuracy, rationality and specialization in a generalized model of collective navigation
Authors: Mann Richard P. , Bailey Joseph D. , Codling Edward A.
Published: September 2024

Animal navigation is a key behavioural process, from localized foraging to global migration. Within groups, individuals may improve their navigational accuracy by following those with more experience or knowledge, by pooling information from many directional estimates (‘many wrongs’) or some combination of these strategies. Previous agent-based simulations have highlighted that homogeneous leaderless groups can improve their collective navigation accuracy when individuals preferentially copy the movement directions of their neighbours while giving a low weighting to their own navigational knowledge. Meanwhile, other studies have demonstrated how specialized leaders may emerge, and that a small number of such individuals can improve group-level navigation performance. However, in general, these earlier results either lack a full mathematical grounding or do not fully consider the effect of individual self-interest. Here we derive and analyse a mathematically tractable model of collective navigation. We demonstrate that collective navigation is compromised when individuals seek to optimize their own accuracy in both homogeneous groups and those with differing navigational abilities. We further demonstrate how heterogeneous navigational strategies (specialized leaders and followers) may evolve within the model. Our results thus unify different lines of research in collective navigation and highlight the importance of individual selection in determining group composition and performance.
Effects of urbanization on cloud-to-ground lightning strike frequency: a global perspective
Authors: Narvaez J. Pablo , Yanoviak Stephen P. , Bitzer Phillip M. , Burchfield Jeffrey C. , Gora Evan M.
Published: September 2024

Urbanization tends to increase local lightning frequency (i.e. the ‘lightning enhancement’ effect). Despite many urban areas showing lightning enhancement, the prevalence of these effects is unknown and the drivers underlying these patterns are poorly quantified. We conducted a global assessment of cloud-to-ground lightning flashes (lightning strikes) across 349 cities to evaluate how the likelihood and magnitude of lightning enhancement vary with geography, climate, air pollution, topography and urban development. The likelihood of exhibiting lightning enhancement increased with higher temperature and precipitation in urban areas relative to their natural surroundings (i.e. urban heat islands and elevated urban precipitation), higher regional lightning strike frequency, greater distance to water bodies and lower elevations. Lightning enhancement was stronger in cities with conspicuous heat islands and elevated urban precipitation effects, higher lightning strike frequency, larger urban areas and lower latitudes. The particularly strong effects of elevated urban temperature and precipitation indicate that these are dominant mechanisms by which cities cause local lightning enhancement.
Enhanced phytoremediation of cadmium-contaminated soil using chelating agents and plant growth regulators: effect and mechanism
Authors: Yang Qiao , Yu Hao , Yang Chen , Zhao Zhongqiu , Ju Zhengshan , Wang Jinman , Bai Zhongke
Published: September 2024

The heavy metal cadmium (Cd) is a major threat to food safety and human health. Phytoremediation is the most widely used remediation technology, and how to improve the remediation efficiency of phytoremediation has become a key issue. In this study, we constructed an intensive phytoremediation technology for remediation of Cd-contaminated soil with biodegradable chelating agent and plant growth regulator combined with maize and investigated the mechanism of this technology. The results showed that the best remediation effect was achieved in the treatment with 10
−6
mol l
−1
gibberellic acid (GA
3
) and 6 mmol kg
−1
aspartate diethoxysuccinic acid (AES) combined with maize. In this treatment, the total biomass and extraction efficiency of maize were 3.6 and 8.67 times higher than those of the control, respectively, and the antioxidant enzyme activities of maize were also increased. The soil was enriched with dominant bacterial genera that promote plant growth and metabolism and tolerance to heavy metal stress, which in turn promoted maize growth and Cd accumulation. Structural equation modelling results indicated a large effect of plant Cd concentration and plant antioxidant enzyme activity on plant Cd extraction. The enhanced phytoremediation technology showed good potential for safe use of Cd-contaminated soil.