bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep brain stimulation: a tale of two targets … and closing the loop
Authors: Zrinzo Ludvic
Published: February 2024

This scientific commentary refers to ‘At home adaptive dual target deep brain stimulation in Parkinson disease with proportional control’ by Schmidt et al. (https://doi.org/10.1093/brain/awad429).
Defining the cross-reactivity between peanut allergens Ara h 2 and Ara h 6 using monoclonal antibodies
Authors: Marini-Rapoport Orlee , Fernández-Quintero Monica L , Keswani Tarun , Zong Guangning , Shim Jane , Pedersen Lars C , Mueller Geoffrey A , Patil Sarita U
Published: February 2024

In peanut allergy, Arachis hypogaea 2 (Ara h 2) and Arachis hypogaea 6 (Ara h 6) are two clinically relevant peanut allergens with known structural and sequence homology and demonstrated cross-reactivity. We have previously utilized X-ray crystallography and epitope binning to define the epitopes on Ara h 2. We aimed to quantitatively characterize the cross-reactivity between Ara h 2 and Ara h 6 on a molecular level using human monoclonal antibodies (mAbs) and structural characterization of allergenic epitopes. We utilized mAbs cloned from Ara h 2 positive single B cells isolated from peanut-allergic, oral immunotherapy–treated patients to quantitatively analyze cross-reactivity between recombinant Ara h 2 (rAra h 2) and Ara h 6 (rAra h 6) proteins using biolayer interferometry and indirect inhibitory ELISA. Molecular dynamics simulations assessed time-dependent motions and interactions in the antibody–antigen complexes. Three epitopes—conformational epitopes 1.1 and 3, and the sequential epitope KRELRNL/KRELMNL—are conserved between Ara h 2 and Ara h 6, while two more conformational and three sequential epitopes are not. Overall, mAb affinity was significantly lower to rAra h 6 than it was to rAra h 2. This difference in affinity was primarily due to increased dissociation of the antibodies from rAra h 6, a phenomenon explained by the higher conformational flexibility of the Ara h 6–antibody complexes in comparison to Ara h 2–antibody complexes. Our results further elucidate the cross-reactivity of peanut 2S albumins on a molecular level and support the clinical immunodominance of Ara h 2.
Evaluating the depression state during perinatal period by non-invasive scalp EEG
Authors: Peng Yueheng , Lv Bin , Yang Qingqing , Peng Yan , Jiang Lin , He Mengling , Yao Dezhong , Xu Wenming , Li Fali , Xu Peng
Published: February 2024

Perinatal depression, with a prevalence of 10 to 20% in United States, is usually missed as multiple symptoms of perinatal depression are common in pregnant women. Worse, the diagnosis of perinatal depression still largely relies on questionnaires, leaving the objective biomarker being unveiled yet. This study suggested a safe and non-invasive technique to diagnose perinatal depression and further explore its underlying mechanism. Considering the non-invasiveness and clinical convenience of electroencephalogram for mothers-to-be and fetuses, we collected the resting-state electroencephalogram of pregnant women at the 38th week of gestation. Subsequently, the difference in network topology between perinatal depression patients and healthy mothers-to-be was explored, with related spatial patterns being adopted to achieve the classification of pregnant women with perinatal depression from those healthy ones. We found that the perinatal depression patients had decreased brain network connectivity, which indexed impaired efficiency of information processing. By adopting the spatial patterns, the perinatal depression could be accurately recognized with an accuracy of 87.88%; meanwhile, the depression severity at the individual level was effectively predicted, as well. These findings consistently illustrated that the resting-state electroencephalogram network could be a reliable tool for investigating the depression state across pregnant women, and will further facilitate the clinical diagnosis of perinatal depression.
An Intelligent Security System Using Enhanced Anomaly-Based Detection Scheme
Authors: Louati Faten , Barika Ktata Farah , Amous Ikram
Published: February 2024

Ensuring the security of computer networks is of utmost importance, and intrusion detection plays a vital role in safeguarding these systems. Traditional intrusion detection systems (IDSs) often suffer from drawbacks like reliance on outdated rules and centralized architectures, limiting their performance in the face of evolving threats and large-scale data networks. To address these challenges, we present an advanced anomaly detection-based IDS that utilizes a decentralized communicative multi-agent reinforcement learning (MARL). In our approach, multiple reinforcement learning agents collaborate in intrusion detection, effectively mitigating the non-stationarity problem and introducing a specialized secure communication method. We further enhance the learning process by incorporating external knowledge. Our approach is evaluated through extensive experiments conducted on the benchmark NSL Knowledge Discovery and Data Mining dataset. These experiments encompass diverse scenarios, involving varying numbers of agents to prove scalability feature. The results underscore the effectiveness of our method, which surpasses the performance of existing state-of-the-art solutions based on MARL, achieving a high accuracy rate of 97.80%.
Borehole Depth Recognition Based on Improved YOLOX Detection
Authors: Ren Dawei , Meng Lingwei , Wang Rui
Published: February 2024

This study proposes a method for recognizing the drill depth in low-light underground environments, with the aim of addressing the issues of low efficiency and susceptibility to manual changes in the current methods. The method is based on an improved You Only Look Once X model. Initially, image data undergo enhancement and annotation. Secondly, it incorporates an attention mechanism to improve the feature extraction capability. The feature pyramid is utilized to minimize feature loss and facilitate better multi-scale feature fusion. Additionally, the loss function is optimized to enhance the localization ability of the prediction box. The enhanced model achieves an accuracy of 91.3$\%$, representing a 4.4$\%$ increase compared to the pre-improvement performance, and demonstrates improved positioning accuracy. Successful drilling depth measurements were carried out with the acquired positioning information.
Temporal relationship between haemodynamic changes and activation of closed-loop stimulation during a tilt-induced vasovagal syncope
Authors: Russo Vincenzo , Tomaino Marco , Parente Erika , Comune Angelo , Giacopelli Daniele , Napoli Paola , Gargaro Alessio , Brignole Michele
Published: February 2024

Aims

A dual-chamber pacemaker with closed-loop stimulation (CLS) mode is effective in reducing syncopal recurrences in patients with asystolic vasovagal syncope (VVS). In this study, we explored the haemodynamic and temporal relationship of CLS during a tilt-induced vasovagal reflex.

Methods and results

Twenty patients underwent a tilt test under video recording 3.9 years after CLS pacemaker implantation. Three patients were excluded from the analysis because of no VVS induced by the tilt test (n = 1) and protocol violation (n = 2). In 14 of the remaining 17 patients, CLS pacing emerged during the pre-syncopal phase of circulatory instability when the mean intrinsic heart rate (HR) was 88 ± 12 b.p.m. and systolic blood pressure (SBP) was 108 ± 19 mmHg. The CLS pacing rate thereafter rapidly increased to 105 ± 14 b.p.m. within a median of 0.1 min [inter-quartile range (IQR), 0.1–0.7 min] when the SBP was 99 ± 21 mmHg. At the time of maximum vasovagal effect (syncope or pre-syncope), SBP was 63 ± 17 mmHg and the CLS rate was 95 ± 13 b.p.m. The onset of CLS pacing was 1.7 min (IQR, 1.5–3.4) before syncope or lowest SBP. The total duration of CLS pacing was 5.0 min (IQR, 3.3–8.3). Closed-loop stimulation pacing was not observed in three patients who had a similar SBP decrease from 142 ± 22 mmHg at baseline to 69 ± 4 mmHg at the time of maximum vasovagal effect, but there was no significant increase in HR (59 ± 1 b.p.m.).

Conclusion

The reproducibility of a vasovagal reflex was high. High-rate CLS pacing was observed early during the pre-syncopal phase in most patients and persisted, although attenuated, at the time of maximum vasovagal effect.

Registration

ClinicalTrials.gov identifier: NCT06038708
Inverse modelling and classification of magnetic responses to improve marine unexploded ordnance rationalization
Authors: Brighouse Jack , Wood Martin , McGregor Eoin , Kirkland Andrew , Sinclair David , Erbs-Hansen Dorthe Reng , Hviid Simon
Published: February 2024

Unexploded ordnance (UXO), often deployed in WWI and WWII, are still present on the seabed posing a risk to seabed construction. UXO surveys identify potential UXO targets which are then investigated and removed where necessary; however, approximately 96 per cent of targets investigated on projects included in this study were non-UXO (false positives). Here we investigate methods of improving statistical confidence in targets picked through the improved classification of magnetic response, utilizing simulation methods and historic data. A simulation of the induced magnetism of UXO was developed to model the most likely dimensions and orientation of a given source item. Modelling results and measured variables were combined in an optimization algorithm, hereon referred to as ‘the classifier’. We document the results of integrating the magnetic responses of 3027 targets from 18 offshore wind projects into the classifier. Five of these projects were performed as tests in which the target results were unknown during classification. Finally, the classifier was deployed on a live project, Hollandse Kust Zuid 3 and 4 Offshore Wind Farm, in which it enabled the removal of 67 targets from the from the 1200-target investigation list. The classifier proved to be a valuable additional tool to assist the target rationalization process, reliably and repeatably distinguishing UXO from other items, thereby reducing false positives and repeatably demonstrating no threshold UXO false negatives. Assumptions and limitations of this methodology were highlighted, which must be understood and considered when integrating this approach on future projects.
Development of a novel hybrid antimicrobial peptide for enhancing antimicrobial spectrum and potency against food-borne pathogens
Authors: Han Jinzhi , Wu Peifen , Yang Jie , Weng Yanlin , Lin Yayi , Chen Zhiying , Yu Fengfan , Lü Xucong , Ni Li
Published: February 2024

Aims

To address the increasingly serious challenge of the transmission of foodbrone pathogens in the food chain.

Methods and results

In this study, we employed rational design strategies, including truncation, amino acid substitution, and heterozygosity, to generate seven engineered peptides with α-helical structure, cationic property, and amphipathic characteristics based on the original Abhisin template. Among them, as the hybird antimicrobial peptide (AMP), AM exhibits exceptional stability, minimal toxicity, as well as broad-spectrum and potent antimicrobial activity against foodborne pathogens. Besides, it was observed that the electrostatic incorporation demonstrates by AM results in its primary targeting and disruption of the cell wall and membrane of Escherichia coli O157: H7 (EHEC) and methicillin-resistant Staphylococcus aureus (MRSA), resulting in membrane perforation and enhanced permeability. Additionally, AM effectively counteracts the deleterious effects of lipopolysaccharide, eradicating biofilms and ultimately inducing the demise of both food spoilage and pathogenic microorganisms.

Conclusions

The findings highlight the significant potential of AM as a highly promising candidate for a novel food preservative and its great importance in the design and optimization of AMP-related agents.
Denoising CSAMT signals in the time domain based on long short-term memory
Authors: Xu Bingcheng , An Zhiguo , Han Ying , Ye Gaofeng
Published: February 2024

Controlled-source audio frequency magnetotellurics (CSAMT) is an artificial-source electromagnetic technique that partially mitigates the limitations of weak natural-field signals. However, practical field surveys inevitably encounter strong interference, severely affecting signal quality. Traditional methods such as Fourier transformation, which directly computes apparent resistivity from frequency-domain information, are inadequate in this context, so we need alternative denoising approaches. However, research on CSAMT denoising is currently limited. Given the excellent performance of long short-term memory (LSTM) neural networks in the processing of magnetotelluric (MT) data, as demonstrated by previous studies, this paper proposes the use of LSTM to denoise CSAMT signals in the time domain. Unlike traditional denoising methods, we aim to directly extract the target frequency signal from the time-series data for denoising. For MT data, target frequency signals and noise are all mixed together, so noise suppression can only be achieved by identifying noise characteristics in the time series. However, unlike MT data, CSAMT data has an artificial transmitting source, and the frequency of the valid signal is fixed within a time interval. This allows for the direct extraction of target frequency signals without considering the complex characteristics of noise. In this study, we developed a neural network based on bidirectional LSTM to accomplish the task of noise suppression. After conducting both simulated and measured data tests, this method was able to, on average, improve the signal-to-noise ratio (SNR) of CSAMT data by approximately 20 dB and partially address the challenge of denoising when the data's SNR falls below 0 dB.
A drying climate and habitat availability drive extirpations of a southward advancing ground squirrel
Authors: Nash Austin L , McCain Christy M
Published: February 2024

Ground squirrels act as important members of grassland ecosystems by serving as both ecosystem engineers and as a prey base for carnivores. There is mounting evidence that climate change is driving ground squirrel population declines. We resurveyed 54 historical localities throughout the Wyoming Basin and western Colorado where Wyoming Ground Squirrel (Urocitellus elegans) specimens were collected to investigate if climate change was driving extirpations at these historically occupied sites. We detected extirpations at 12 sites and used binomial generalized linear models in an information-theoretic framework to investigate if climate change was associated with these extirpations. Additionally, we investigated if land cover change was associated with persistence and if land cover ameliorated or exacerbated the effects of climate change. We found that changes in climate, especially increasingly dry summer air and increasing mean summer temperatures, were associated with a reduced probability that U. elegans persisted at a historically occupied site. In addition, we found that current forest cover at a site and increasing rangeland cover at the regional level were associated with reduced probability that U. elegans persisted, although these associations were weaker than the climate associations. The effects of climate change and land cover change did not interact. Our findings build on mounting evidence that montane-associated ground squirrels throughout the Western United States are negatively impacted by climate change. The reduction in ground squirrel abundance or their extirpation due to climate change could lead to changes in ecosystem structure or reductions in trophic complexity.
Diversity of MHC class II DRB alleles in the Northern chamois genus Rupicapra
Authors: Stipoljev Sunčica , Buzan Elena , Iacolina Laura , Safner Toni , Rezić Andrea , Galov Ana , Križanović Krešimir , Ambarlı Hüseyin , Arnal MariaCruz , Babaev Elmar , Bego Ferdinand , Farkas Attila , Gačić Dragan , Lazar Peter , Maletić Vladimir , Markov Georgi , Milošević Dragana , Papaioannou Haritakis , Scandura Massimo , Šprem Nikica
Published: February 2024

Major histocompatibility complex (MHC) genes are commonly used markers for monitoring adaptive genetic and evolutionary potential of species. In this study, we investigated genetic variation of the MHC class II DRB locus in the chamois genus Rupicapra by using next-generation sequencing. Sequencing of 102 samples led to the identification of 25 alleles, 11 of which are novel. The high ratio of the relative rates of nonsynonymous to synonymous mutations (dN/dS) suggests a signal of positive selection on this locus. We analyzed patterns of genetic variation within and among 2 subspecies of Northern Chamois and compared them to previously published studies using neutral markers to provide a basis for assessing the effects of demographic processes. Our analyses have shown that alleles are likely to be maintained by balancing selection in different populations with similar frequencies and that this mechanism also works in small, isolated populations that are strongly affected by genetic drift.
Returning to Work After Traumatic Spine Fractures: Current Status in a Military Hospital
Authors: Alhabeeb Abdulrahman Yousef , Konbaz Faisal , Aleissa Sami , Alhamed Ghada S , Alhowaish Thamer S , Alhamadh Moustafa S , Masuadi Emad , Abalkhail Majed , AlHelal Fahad , Bourghli Anouar
Published: February 2024

Introduction

The consequences of traumatic spine fracture (TSF) are complex and have a major burden on patients’ social life and financial status. In this study, we aimed to investigate the return to work (RTW) after surgically treated TSFs, develop eventual predictors of delayed or failure to RTW, and assess narcotics use following such injuries.

Methods

This was a single-center retrospective cohort study that was performed in a tertiary care center. TSF patients who required surgical intervention from 2016 to 2021 were enrolled. Demographic, operative, and complication data, as well as narcotics use, were recorded. RTW was modeled using multivariate logistic regression analysis.

Results

Within the 173 patients with TSF, male patients accounted for 82.7%, and motor vehicle accidents were the most common mechanism of injury (80.2%). Neurologically intact patients represented 59%. Only 38.15% returned to work after their injury. Majority of the patients didn’t use narcotics more than 1 week after discharge (93.1%). High surgical blood loss, operation time, and hospital length of stay were significantly associated with not returning to work. In multivariant regression analysis, every increase of 100 ml of surgical blood loss was found to decrease the chance of RTW by 25% (P = 0.04). Furthermore, every increase of one hour in operation time decreases the chance of RTW by 31% (P = 0.03).

Conclusion

RTW is an important aspect that needs to be taken into consideration by health care providers. We found that age and high surgery time, blood loss, and hospital stay are significantly impacting patients’ RTW after operated TSF.
Catalogue of nearby blue and near-solar gas metallicity SDSS dwarf galaxies
Authors: Guo Yan , Sengupta Chandreyee , Scott Tom C , Lagos Patricio , Luo Yu
Published: February 2024

A less explored aspect of dwarf galaxies is their metallicity evolution. Generally, dwarfs have lower metallicities than Hubble sequence late-type galaxies, but in reality, dwarfs span a wide range of metallicities with several open questions regarding the formation and evolution of the lowest and the highest metallicity dwarfs. We present a catalogue of 3459 blue, nearby, star-forming dwarf galaxies extracted from SDSS DR-16 including calculation of their metallicities using the mean of several calibrators. To compile our catalogue we applied redshift, absolute magnitude, stellar mass, optical diameter, and line flux signal-to-noise criteria. This produced a catalogue from the upper end of the dwarf galaxy stellar mass range. Our catalogued dwarfs have blue g – i colours and Hβ equivalent widths, indicative of having undergone a recent episode of star formation, although their star formation rates (SFRs) suggest only a moderate to low enhancement in star formation, similar to the SFRs in low surface brightness and evolved tidal dwarfs. While the catalogued dwarfs cover a range of metallicities, their mean metallicity is ∼0.2 dex below solar metallicity, indicating relatively chemically evolved galaxies. The vast majority of the catalogue, with clean photometry, are relatively isolated dwarfs with only modest SFRs and a narrow range of g – i colour, consistent with internally driven episodic mild bursts of star formation. The presented catalogue’s robust metallicity estimates for nearby SDSS dwarf galaxies will help target future studies to understand the physical processes driving the metallicity evolution of dwarfs.
AT2020ohl: its nature and probable implications
Authors: Roy Rupak , Mandal Samir , Sahu D K , Anupama G C , Nandi Sumana , Kumar Brijesh
Published: February 2024

ASASSN-20hx, a.k.a AT2020ohl, is an ambiguous nuclear transient, which was discovered in the nearby galaxy NGC6297 by the All-Sky Automated Survey for Supernovae. We have investigated the evolution of AT2020ohl using a multiwavelength data set to explain the geometry of the system and the energy radiated by it between X-ray and radio wavelengths. Our X-ray, UV/optical, and radio observations of the object jointly clarify the association of AT2020ohl with the nuclear activity of NGC6297. We detected radio counterpart of AT2020ohl 111 and 313 d after the discovery in Jansky Very Large Array X-band with flux densities 47 ± 14 and 34 ± 3 $\mu$Jy, respectively. Using multiwavelength data analysis, we nullify the possibility of associating any stellar disruption process with this event. We found some evidence showing that the host galaxy is a merger remnant, so the possibility of a binary supermassive black hole (SMBH) system cannot be ruled out. The central SMBH has a mass of ∼1.2 × 107 M⊙. We propose the accretion disc activity as the origin of AT2020ohl – it is either due to disc accretion event on to the central SMBH or due to the sudden accretion activity in a pre-existing accretion disc of the system during the interaction of two SMBHs which became gravitationally bound during a merger process. However, we also admit that with the existing data set, it is impossible to say definitively, among these two probabilities, which one is the origin of this nuclear transient.
Time evolution of X-ray bright points observed with NuSTAR
Authors: Paterson Sarah , Hannah Iain G , Grefenstette Brian W , Hudson Hugh S , Krucker Säm , Glesener Lindsay , White Stephen M , Smith David M
Published: February 2024

We present analysis on two X-ray bright points observed over several hours during the recent solar minimum (2020 February 21 and 2020 September 12–13) with the Nuclear Spectroscopic Telescope Array (NuSTAR), a sensitive hard X-ray imaging spectrometer. This is so far the most detailed study of bright points in hard X-rays, emission which can be used to search for faint hot and/or non-thermal sources. We investigate the bright points’ time evolution with NuSTAR, and in extreme ultraviolet (EUV) and soft X-rays with Solar Dynamic Observatory/Atmospheric Imaging Assembly (SDO/AIA) and Hinode/X-Ray Telescope. The variability in the X-ray and EUV time profiles is generally not well matched, with NuSTAR detecting spikes that do not appear in EUV. We find that, for the 2020 February bright point, the increased X-ray emission during these spikes is due to material heated to ∼ 4.2–4.4 MK (found from fitting the X-ray spectrum). The 2020 September bright point also shows spikes in the NuSTAR data with no corresponding EUV signature seen by SDO/AIA, though in this case, it was due to an increase in emission measure of material at ∼ 2.6 MK and not a significant temperature change. So, in both cases, the discrepancy is likely due to the different temperature sensitivity of the instruments, with the X-ray variability difficult to detect in EUV due to cooler ambient bright point emission dominating. No non-thermal emission is detected, so we determine upper limits finding that only a steep non-thermal component between 3 and 4 keV could provide the required heating whilst being consistent with a null detection in NuSTAR.
cecilia: a machine learning-based pipeline for measuring metal abundances of helium-rich polluted white dwarfs
Authors: Badenas-Agusti Mariona , Viaña Javier , Vanderburg Andrew , Blouin Simon , Dufour Patrick , Xu Siyi , Sha Lizhou
Published: February 2024

Over the past several decades, conventional spectral analysis techniques of polluted white dwarfs have become powerful tools to learn about the geology and chemistry of extrasolar bodies. Despite their proven capabilities and extensive legacy of scientific discoveries, these techniques are, however, still limited by their manual, time-intensive, and iterative nature. As a result, they are susceptible to human errors and are difficult to scale up to population-wide studies of metal pollution. This paper seeks to address this problem by presenting cecilia, the first machine learning (ML)-powered spectral modelling code designed to measure the metal abundances of intermediate-temperature (10 000 ≤ Teff ≤ 20 000 K), Helium-rich polluted white dwarfs. Trained with more than 22 000 randomly drawn atmosphere models and stellar parameters, our pipeline aims to overcome the limitations of classical methods by replacing the generation of synthetic spectra from computationally expensive codes and uniformly spaced model grids, with a fast, automated, and efficient neural-network-based interpolator. More specifically, cecilia combines state-of-the-art atmosphere models, powerful artificial intelligence tools, and robust statistical techniques to rapidly generate synthetic spectra of polluted white dwarfs in high-dimensional space, and enable accurate (≲0.1 dex) and simultaneous measurements of 14 stellar parameters – including 11 elemental abundances – from real spectroscopic observations. As massively multiplexed astronomical surveys begin scientific operations, cecilia’s performance has the potential to unlock large-scale studies of extrasolar geochemistry and propel the field of white dwarf science into the era of Big Data. In doing so, we aspire to uncover new statistical insights that were previously impractical with traditional white dwarf characterization techniques.
Horizontal branch structure, age, and chemical composition for very metal-poor extragalactic globular clusters
Authors: Sharina M E , Maricheva M I , Kniazev A Y , Shimansky V V , Acharova I A
Published: February 2024

This paper presents the results of analysing the integrated light (IL) low-resolution spectra of globular clusters (GCs) in the M31 and Centaurus A groups of galaxies. The sample consists of eight very metal-poor GCs ($\rm [Fe/H]\le -2$ dex) with high signal-to-noise ratio spectra acquired with the telescopes: the 6-m SAO RAS (BTA), the Southern African Large (SALT), and the 6.5-m Magellan (MMT). We study the influence of contribution of the horizontal branch stars on the hydrogen Balmer line profiles in the IL spectra. By modelling the Balmer lines, as well as the metal lines in the observed spectra, we determine the optimum parameters of stellar evolution isochrones and, consequently, the parameters of the atmospheres of the cluster stars. For all the studied GCs, the parameters of horizontal branch stars set by the selected isochrones, the corresponding ages, and carbon abundances are presented for the first time. The abundances of several other elements (Mg, Ca, Ti, Cr, and Mn) were determined for five GCs for the first time. All the studied GCs have blue horizontal branches and are older than 10 Gyr. Their chemical abundances, with the exception of Mg and Mn, are in good agreement with the abundances of stars in the Galactic field. The reasons of low [Mg/Fe] and of high [Mn/Fe] are discussed. Study of the fundamental properties of stellar populations in old GCs facilitates a better understanding of the formation processes of their parent galaxies and nucleosynthesis in the early Universe.
Chromatin damage generated by DNA intercalators leads to degradation of RNA Polymerase II
Authors: Espinoza Jaime A , Kanellis Dimitris C , Saproo Sheetanshu , Leal Karla , Martinez Johana Fernandez , Bartek Jiri , Lindström Mikael S
Published: February 2024

In cancer therapy, DNA intercalators are mainly known for their capacity to kill cells by inducing DNA damage. Recently, several DNA intercalators have attracted much interest given their ability to inhibit RNA Polymerase I transcription (BMH-21), evict histones (Aclarubicin) or induce chromatin trapping of FACT (Curaxin CBL0137). Interestingly, these DNA intercalators lack the capacity to induce DNA damage while still retaining cytotoxic effects and stabilize p53. Herein, we report that these DNA intercalators impact chromatin biology by interfering with the chromatin stability of RNA polymerases I, II and III. These three compounds have the capacity to induce degradation of RNA polymerase II and they simultaneously enable the trapping of Topoisomerases TOP2A and TOP2B on the chromatin. In addition, BMH-21 also acts as a catalytic inhibitor of Topoisomerase II, resembling Aclarubicin. Moreover, BMH-21 induces chromatin trapping of the histone chaperone FACT and propels accumulation of Z-DNA and histone eviction, similarly to Aclarubicin and CBL0137. These DNA intercalators have a cumulative impact on general transcription machinery by inducing accumulation of topological defects and impacting nuclear chromatin. Therefore, their cytotoxic capabilities may be the result of compounding deleterious effects on chromatin homeostasis.
Retention of the RNA ends provides the molecular memory for maintaining the activation of the Csm complex
Authors: Irmisch Patrick , Mogila Irmantas , Samatanga Brighton , Tamulaitis Gintautas , Seidel Ralf
Published: February 2024

The type III CRISPR-Cas effector complex Csm functions as a molecular Swiss army knife that provides multilevel defense against foreign nucleic acids. The coordinated action of three catalytic activities of the Csm complex enables simultaneous degradation of the invader's RNA transcripts, destruction of the template DNA and synthesis of signaling molecules (cyclic oligoadenylates cAn) that activate auxiliary proteins to reinforce CRISPR-Cas defense. Here, we employed single-molecule techniques to connect the kinetics of RNA binding, dissociation, and DNA hydrolysis by the Csm complex from Streptococcus thermophilus. Although single-stranded RNA is cleaved rapidly (within seconds), dual-color FCS experiments and single-molecule TIRF microscopy revealed that Csm remains bound to terminal RNA cleavage products with a half-life of over 1 hour while releasing the internal RNA fragments quickly. Using a continuous fluorescent DNA degradation assay, we observed that RNA-regulated single-stranded DNase activity decreases on a similar timescale. These findings suggest that after fast target RNA cleavage the terminal RNA cleavage products stay bound within the Csm complex, keeping the Cas10 subunit activated for DNA destruction. Additionally, we demonstrate that during Cas10 activation, the complex remains capable of RNA turnover, i.e. of ongoing degradation of target RNA.
AGAMOUS-LIKE24 controls pistil number in Japanese apricot by targeting the KNOTTED1-LIKE gene KNAT2/6-a
Authors: Bai Yang , Zhou Pengyu , Ni Zhaojun , Iqbal Shahid , Ouma Kenneth Omondi , Huang Xiao , Gao Feng , Ma Chengdong , Shi Ting , Gao Zhihong
Published: February 2024

The formation of multi-pistil flowers reduces the yield and quality in Japanese apricot (Prunus mume). However, the molecular mechanism underlying the formation of multi-pistil flowers remains unknown. In the current study, overexpression of PmKNAT2/6-a, a class I KNOTTED1-like homeobox (KNOX) member, in Arabidopsis (Arabidopsis thaliana) resulted in a multi-pistil phenotype. Analysis of the upstream regulators of PmKNAT2/6-a showed that AGAMOUS-like 24 (PmAGL24) could directly bind to the PmKNAT2/6-a promoter and regulate its expression. PmAGL24 also interacted with Like Heterochromatin Protein 1 (PmLHP1) to recruit lysine trimethylation at position 27 on histone H3 (H3K27me3) to regulate PmKNAT2/6-a expression, which is indirectly involved in multiple pistils formation in Japanese apricot flowers. Our study reveals that the PmAGL24 transcription factor, an upstream regulator of PmKNAT2/6-a, regulates PmKNAT2/6-a expression via direct and indirect pathways and is involved in the formation of multiple pistils in Japanese apricot.
A Trinitarian Reading of Gerard Manley Hopkins’s ‘The Windhover’
Authors: Hawlin Stefan
Published: February 2024

The rhetorical and emotional verve of ‘The Windhover’ reflect not the moment of stasis of Christ’s cross but the energy of Trinitarian interrelation in creation. Readings of the sonnet usually foreground the second divine person. Countering such a perspective, this essay rehearses the Scholastic theology and the Scholastically based faith that the poet took for granted in the original moment of experience and in the moment of composition, and so reads the sonnet in a more fully Trinitarian way. For Hopkins the energetic dynamic of love and relation within the Trinity is that into which he is drawn via the creation made through Christ, the Word (John 1:3, Col. 1:16), and as used here the energy of the sonnet form is his response to this. The Athanasian Creed and the ‘Veni Creator Spiritus’ are identified as neglected Trinitarian intertexts. Hopkins believed, in Ignatian terms, that Christ ‘labours for me in all things created on the face of the earth’; and so, in the poem, Christ works dynamically through the Holy Spirit, ‘the fire’ (l. 10) who is Love itself, the vector of bird–poet interrelation, engaging him with the windhover and awakening his delight. The sonnet is the poet’s open acknowledgement of the love of the Triune tri-personal God which greets him every moment in the humblest glories of creation.
The Temptation of Social Networks under Job Search Frictions
Authors: Matsuda Norihiko , Nomura Shinsaku
Published: February 2024

This paper presents descriptive evidence that although social networks are helpful to find jobs, the jobs found through social networks tend to be mismatched. The paper uses nationally representative matched employer–employee data in Bangladesh that include direct measures of match quality. Less educated and seemingly poorer workers are more likely to have found their jobs through social networks. Compared to workers at the same occupation level in the same firm who were matched through formal channels, those matched through social networks found their jobs quicker but have lower match quality and earn less. The mechanism, suggested by a theoretical model, is as follows: even when social networks are connected to mismatched jobs, workers can be tempted to use social networks to find mismatched jobs for fear of finding nothing. This temptation is stronger for less skilled and poorer workers, because costly formal channels are less rewarding and affordable for them.
Evaluation of the Maryland Next Gen Test Bank Project: Implications and Recommendations
Authors: Hensel Desirée , Billings Diane M. , Wiseman Rebecca
Published: February 2024

AIM

The aim of this study was to evaluate the development and impact of a project to create a statewide test bank of Next Generation NCLEX®-style items.

BACKROUND

Using a train-the-trainer model, champions created an open access resource of Next Generation NCLEX-style items to use to teach clinical judgment and then trained peers on item writing and test bank use.

METHOD

Stufflebeam’s CIPP (context, inputs, process, and products) model provided the framework for the evaluation. Data were synthesized from multiple sources including participation rates, item utilization, and survey data.

RESULTS

Twenty faculty from 13 schools were trained as champions and submitted 54 case studies, 33 bowties, and 21 trend items to the test bank. Items were used over 60,000 times in the first year.

CONCLUSION

The statewide test bank met a need for more teaching resources. The train-the-trainer model was an effective strategy for helping faculty learn to prepare for Next Generation NCLEX.
North Carolina Medicaid System Perspectives on Substance Use Disorder Treatment Policy Changes During the COVID-19 Pandemic
Authors: Hughes Phillip M. , Easterly Caleb W. , Thomas Kathleen C. , Shea Christopher M. , Domino Marisa Elena
Published: February 2024

Objective

This study aimed to describe perspectives from stakeholders involved in the Medicaid system in North Carolina regarding substance use disorder (SUD) treatment policy changes during the coronavirus disease 2019 pandemic.

Methods

We conducted semistructured interviews in early 2022 with state agency representatives, Medicaid managed care organizations, and Medicaid providers (n = 22) as well as 3 focus groups of Medicaid beneficiaries with SUD (n = 14). Interviews and focus groups focused on 4 topics: policies, meeting needs during COVID, demand for SUD services, and staffing.

Results

Overall, policy changes, such as telehealth and take-home methadone, were considered beneficial, with participants displaying substantial support for both policies. Shifting demand for services, staffing shortages, and technology barriers presented significant challenges. Innovative benefits and services were used to adapt to these challenges, including the provision of digital devices and data plans to improve access to telehealth.

Conclusions

Perspectives from Medicaid stakeholders, including state organizations to beneficiaries, support the continuation of SUD policy changes that occurred. Staffing shortages remain a substantial barrier. Based on the participants' positive responses to the SUD policy changes made during the coronavirus disease 2019 pandemic, such as take-home methadone and telehealth initiation of buprenorphine, these changes should be continued. Additional steps are needed to ensure payment parity for telehealth services.
Multiple fluoroscopic views, including an external rotation-adduction view, are required to detect uncontained screws in the femoral neck
Authors: Campbell Sean T. , Cheema Amarpal , Schimizzi Gregory V. , Klinger Craig , Mintz Douglas , Dziadosz Daniel , Ricci William M.
Published: February 2024

Introduction:

Peripheral screws in the femoral neck are often used for fixation of femoral neck fractures. The posterior-cranial screw can violate the femoral head blood supply if it is extra-osseous, and can be difficult to image intraoperatively. The purpose of this study was to identify whether any specific radiographic views were superior at detecting an uncontained screw in the femoral neck. Additionally, the external rotation-adduction view was defined and its efficacy at detecting an unsafe posterior cranial screw assessed.

Methods:

A radiographic study using three-dimensional (3D) computed tomography scanswas performed at a single institution academic hospital. Forty-six patients with normal CT scans of the pelvis were included. Cannulated screws were digitally templated on 3D renderings of the femoral neck in an inverted triangle configuration. Each screw was systematically moved to a position where it was uncontained. Ghost images were created, and the pelvis rotated to simulate obtaining various iterations of a lateral view of the proximal femur. The ability of a given radiographic view to detect an uncontained screw was determined.

Results:

A flat-lateral view detected 72% of unsafe anterior screw, while a neck-shaft colinear view detected 98%. The flat lateral view detected 61% of unsafe posterior cranial screws, while a new external rotation-adduction view identified 100% of unsafe posterior cranial screws.

Conclusions:

Multiple radiographic views should be obtained to assess screw safety when treating femoral neck fractures with peripherally placed screws. The external rotation-adduction view may be useful for detection of uncontained posterior cranial screws.

Level of evidence:

III
How Does Resorption Differ Among Single-Level and Multilevel Lumbar Disc Herniations? A Prospective Multi-Imaging and Clinical Phenotype Study
Authors: Hornung Alexander L. , Rudisill Samuel S. , Barajas J. Nicolas , Harada Garrett , Fitch Ashlyn A. , Leonard Skylar F. , Roberts Ashley C. , An Howard S. , Albert Hanne B. , Tkachev Alexander , Samartzis Dino
Published: February 2024

Study Design.

Prospective, case series.

Objective.

To identify and characterize any differences in specific patient factors, MRI findings, features of spontaneous disc resorption, and outcomes between patients with single-level and multilevel LDH.

Background.

Lumbar disc herniation (LDH) is one of the most common spinal pathologies worldwide. Though many cases of LDH resolve by spontaneous resorption, the mechanism underlying this “self-healing” phenomenon remains poorly understood, particularly in the context of multilevel herniations.

Methods.

A one-year prospective study was conducted of patients presenting with acute symptomatic LDH between 2017 and 2019. Baseline demographics, herniation characteristics, and MRI phenotypes were recorded before treatment, which consisted of gabapentin, acupuncture, and the avoidance of inflammatory-modulating medications. MRIs were performed approximately every three months after the initial evaluation to determine any differences between patients with single-level and multilevel LDH.

Results.

Ninety patients were included, 17 demonstrated multilevel LDH. Body mass index was higher among patients with multilevel LDH (P<0.001). Patients with multilevel LDH were more likely to exhibit L3/L4 inferior endplate defects (P=0.001), L4/L5 superior endplate defects (P=0.012), and L4/L5 inferior endplate defects (P=0.020) on MRI. No other differences in MRI phenotypes (e.g. Modic changes, osteophytes, etc.) existed between groups. Resorption rate and time to resolution did not differ between those with single-level and multilevel LDH.

Conclusions.

Resorption rates were similar between single-level and multilevel LDH at various time points throughout one prospective assessment, providing insights that disc healing may have unique programmed signatures. Compared with those with single-level LDH, patients with multilevel herniations were more likely to have a higher BMI, lesser initial axial and sagittal disc measurements, and endplate defects at specific lumbar levels. In addition, our findings support the use of conservative management in patients with LDH, regardless of the number of levels affected.

Level of Evidence:

Level 3.
Prevalence of Keratoconus Among High School Students in Southern Brazil: A Community-Based Study
Authors: de Azevedo Magalhães Otavio , Pagano Bruna Nunes , Grellmann Luana Veber , Zago Victor Sanchez , Kronbauer Claudia Leite
Published: February 2024

Objectives:

This study aimed to determine the prevalence of keratoconus (KC) in teenagers who live in Southern Brazil and detect any possible associated factors.

Methods:

This prospective, observational, mobile clinic–based cross-sectional study collected data from students between 14 and 21 years from seven high schools who were living in the Greater Porto Alegre metropolitan region in Southern Brazil. Subjects were clinically surveyed and examined using a slitlamp and rotational Scheimpflug corneal tomography system. All data were collected at the mobile clinic during a single visit.

Results:

Eight-hundred twenty-six students were evaluated (357 boys and 469 girls) with an average age of 16.7±1.2 years. Six subjects were classified as having KC (four girls), yielding a prevalence rate of 0.73% (95% confidence interval, 0.27%–1.57%) or one per 137 teenagers in Southern Brazil. Logistic regression showed an association between KC and positive history of eye rubbing (P=0.02).

Conclusion:

According to our investigation, this is the first KC prevalence study in South America using the latest technologies (Scheimpflug imaging). The prevalence of KC among teenagers in Southern Brazil is within the highest reported worldwide. We also found an association between KC and history of eye rubbing. Keratoconus is not an uncommon disorder in our population, and the efforts to identify the disease and reduce its risk factors in an earlier phase are justified.
Prevalence of Keratoconus Based on Scheimpflug Corneal Tomography Metrics in a Pediatric Population From a Chicago-Based School Age Vision Clinic
Authors: Harthan Jennifer S. , Gelles John D. , Block Sandra S. , Tullo William , Morgenstern Andrew S. , Su Becky , Chung Daniel , Yu Austin , Greenstein Steven A. , Hersh Peter S. , Eiden Steven Barry
Published: February 2024

Purpose:

Determine the pediatric prevalence of keratoconus (KC) using Scheimpflug corneal tomography.

Methods:

A prospective observational study was done on subjects aged 3 to 18 years at the Princeton Vision Clinic, Chicago, IL. Scheimpflug tomography (Pentacam HR, OCULUS Optikgerate GmbH) scans (Belin/Ambrósio Enhanced Ectasia BAD3) yielded BAD Final D (Final D) and Back Elevation at the Thinnest Point (BETP) measurements. Criteria differentiating non-KC from KC suspects & KC were, Non-
KC—Final D <2.00 in both eyes; KC
suspect—Final D ≥2.00 and <3.00 in combination with BETP ≥18 μm for myopia and ≥28 μm for hyperopia/mixed astigmatism in at least one eye; and KC—Final D of ≥3.00 with BETP ≥18 μm for myopia or ≥28 μm for hyperopia/mixed astigmatism in at least one eye. Two thousand two hundred and six subjects were recorded, removing duplicate and poor-quality scans leaving 2007 subjects.

Results:

Of 2007 subjects, six were classified as KC—prevalence of 1:334, three subjects were KC
suspects—prevalence of 1:669, and total prevalence of KC suspects and KC was 1:223.

Conclusion:

The prevalence of KC in children is higher than previously reported, emphasizing the importance of sensitive screening for KC at its earliest manifestation as standard in pediatric comprehensive eye examinations.
The Conjunctival Microbiome and Dry Eye: What We Know and Controversies
Authors: Shih Kendrick C. , Tong Louis
Published: February 2024

Dry eye disease is a common multifactorial condition that may be idiopathic or associated with autoimmune conditions, such as Sjogren syndrome. Commensal microorganisms modify immune responses, so it is relevant to understand how they modify such immune-mediated diseases. Microbiota in the gut regulate inflammation in the eye, and conversely, severe inflammation of the ocular surface results in alteration of gut microbiome. The conjunctiva microbiome can be analyzed using 16S or shotgun metagenomics. The amount of microbial DNA in ocular surface mucosa relative to human DNA is limited compared with the case of the intestinal microbiome. There are challenges in defining, harvesting, processing, and analyzing the microbiome in the ocular surface mucosa. Recent studies have shown that the conjunctiva microbiome depends on age, presence of local and systemic inflammation, and environmental factors. Microbiome-based therapy, such as the use of oral probiotics to manage dry eye disease, has initial promising results. Further longitudinal studies are required to investigate the alteration of the conjunctival microbiome after local therapy and surgery.