bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel algorithm for non-invasive estimation of left atrial pressure in patients with atrial fibrillation
Authors: Seo Jiwon , Yu Hee Tae , Kim In-Soo , Kim Tae-Hoon , Joung Boyoung , Pak Hui-Nam , Cho Iksung , Shim Chi Young , Hong Geu-Ru , Ha Jong-Won
Published: December 2024

Aims

Determining elevated left atrial (LA) pressure is crucial in patients with atrial fibrillation (AF), yet non-invasive estimation using echocardiography remains unclear. This study aimed to identify useful echocardiographic indices for identifying elevated LA pressure in patients with AF.

Methods and results

Patients with paroxysmal or persistent AF referred for catheter ablation at two tertiary hospitals were prospectively enrolled. Mean LA pressure was measured immediately after transseptal puncture. Elevated mean LA pressure was defined as ≥15 mmHg. Transthoracic echocardiography was performed to acquire the guideline-recommended parameters. A total of 176 patients were included, and 63 (36%) patients had a mean LA pressure ≥15 mmHg. Patients with elevated LA pressure had more frequent hypertension, larger LA, higher septal E/e′, and worse LA strain than the remaining patients. The correlations between mean LA pressure and each echocardiographic parameter were weak. Septal E/e′ ratio showed the best correlation with mean LA pressure (r = 0.351, P < 0.001), and septal E/e′ ratio ≥11 was the best parameter (area under the curve = 0.7, sensitivity = 65%, specificity = 73%, accuracy = 70%) to identify elevated mean LA pressure. A hierarchical algorithm consisting of septal E/e′ ratio, LA reservoir strain, and LA volume index improved identification of patients with elevated mean LA pressure (sensitivity = 61%, specificity = 91%, accuracy = 80%).

Conclusion

In patients with AF, the septal E/e′ ratio was the best single parameter for identifying elevated mean LA pressure. A hierarchical algorithm combining the septal E/e′ ratio, LA reservoir strain, and LA volume index helps identify elevated LA pressure in patients with AF.
Safety of prolonged bilateral antegrade cerebral perfusion in aortic arch surgery with moderate hypothermia
Authors: Hohri Yu , Rajesh Kavya , Murana Giacomo , Castagnini Sabrina , Bianco Edoardo , Zhao Yanling , Kurlansky Paul , Pacini Davide , Takayama Hiroo
Published: December 2024

OBJECTIVES

This study investigates the impact of bilateral antegrade cerebral perfusion (ACP) time on outcomes in aortic arch surgery.

METHODS

In total, 961 patients underwent either hemiarch (n = 385) or total arch replacement (n = 576) with bilateral ACP and moderate hypothermia management between 2006 and 2020 across 2 aortic centres. ACP time was categorized into 4 groups (≤30 min: n = 169, 30–60 min: n = 298, 60–90 min: n = 261, >90 min: n = 233). Inverse probability of treatment weighting yielded a well-balanced cohort among the 4 groups except for the cannulation site. Adjusted cubic spline and multivariable logistic analysis were performed, controlling for surgical procedure, cannulation site and cardiopulmonary bypass (CPB) time, to identify the relationship between ACP time and major in-hospital complications including mortality, stroke, acute renal failure and prolonged ventilation.

RESULTS

There remained a significant difference in surgical procedures and CPB time in the matched cohort. The incidences of mortality and stroke did not show significant trend (P = 0.052 and 0.717, respectively). Cubic spline curves showed that odds ratios did not increase linearly for any complications with increasing ACP time. Furthermore, ACP time, even exceeding 90 min, was not associated with complication rates [mortality: odds ratio = 1.459 (0.368–6.049), P = 0.595; stroke: 0.310 (0.058–1.635), P = 0.166; renal failure: 1.744 (0.521–6.094), P = 0.374; prolonged ventilation: 1.502 (0.535–4.286), P = 0.442], whereas CPB time was associated with mortality and prolonged ventilation.

CONCLUSIONS

Even when ACP time exceeded 90 min, it was not associated with major in-hospital complications, questioning its validity as a marker for surgical insult.
Herbivory and water availability interact to shape the adaptive landscape in the perennial forb, Boechera stricta
Authors: Jameel M Inam , Duncan Lisa , Mooney Kailen , Anderson Jill T
Published: December 2024

Abiotic and biotic factors interact to influence phenotypic evolution; however, identifying the causal agents of selection that drive the evolution and expression of traits remains challenging. In a field common garden, we manipulated water availability and herbivore abundance across 3 years, and evaluated clinal variation in functional traits and phenology, phenotypic plasticity, local adaptation, and selection using diverse accessions of the perennial forb, Boechera stricta. Consistent with expectations, drought stress exacerbated damage from herbivores. We found significant plasticity and genetic clines in foliar and phenological traits. Water availability and herbivory interacted to exert selection, even on traits like flowering duration, which showed no clinal variation. Furthermore, the direction of selection on specific leaf area in response to water availability mirrored the genetic cline and plasticity, suggesting that variation in water levels across the landscape influences the evolution of this trait. Finally, both herbivory and water availability likely contribute to local adaptation. This work emphasizes the additive and synergistic roles of abiotic and biotic factors in shaping phenotypic variation across environmental gradients.
The GATA factor AreB regulates nitrogen metabolism, fungal development, and aflatoxin production in Aspergillus flavus
Authors: Zhi Qing-Qing , Wang Zhen-Long , Yuan Pei-Bo , He Lei , He Zhu-Mei
Published: December 2024

Nitrogen is important for fungal growth and development, and the GATA transcription factor AreA has been widely studied as a key regulator of nitrogen catabolite repression (NCR) in many fungi. However, AreB, another GATA transcription factor in the NCR pathway, remains less studied, and its role in Aspergillus flavus is still unclear. In this study, we characterized areB in A. flavus and investigated its role in regulating nitrogen utilization, fungal growth, and aflatoxin production. The areB gene produces three transcripts, with areB-α being the most abundantly expressed, particularly under nitrogen-limited conditions. Gene expression analysis via qPCR confirmed that areB acts as a negative regulator of NCR, as its deletion led to the upregulation of NCR-related genes under nitrogen-limiting conditions. Gene function analysis of areB revealed that its deletion impaired hyphal growth, reduced conidia production, and delayed conidial germination. Additionally, deletion of areB led to increased aflatoxin production, particularly under less favorable nitrogen sources, while overexpression of areB reduced aflatoxin levels. Furthermore, areB influenced sclerotia formation in a nitrogen-source-dependent manner. These findings reveal the multifaceted role of areB in nitrogen regulation, fungal development, and secondary metabolism, offering insights for controlling aflatoxin contamination and fungal growth.
PlasGO: enhancing GO-based function prediction for plasmid-encoded proteins based on genetic structure
Authors: Ji Yongxin , Shang Jiayu , Guan Jiaojiao , Zou Wei , Liao Herui , Tang Xubo , Sun Yanni
Published: December 2024

Background

Plasmid, as a mobile genetic element, plays a pivotal role in facilitating the transfer of traits, such as antimicrobial resistance, among the bacterial community. Annotating plasmid-encoded proteins with the widely used Gene Ontology (GO) vocabulary is a fundamental step in various tasks, including plasmid mobility classification. However, GO prediction for plasmid-encoded proteins faces 2 major challenges: the high diversity of functions and the limited availability of high-quality GO annotations.

Results

In this study, we introduce PlasGO, a tool that leverages a hierarchical architecture to predict GO terms for plasmid proteins. PlasGO utilizes a powerful protein language model to learn the local context within protein sentences and a BERT model to capture the global context within plasmid sentences. Additionally, PlasGO allows users to control the precision by incorporating a self-attention confidence weighting mechanism. We rigorously evaluated PlasGO and benchmarked it against 7 state-of-the-art tools in a series of experiments. The experimental results collectively demonstrate that PlasGO has achieved commendable performance. PlasGO significantly expanded the annotations of the plasmid-encoded protein database by assigning high-confidence GO terms to over 95% of previously unannotated proteins, showcasing impressive precision of 0.8229, 0.7941, and 0.8870 for the 3 GO categories, respectively, as measured on the novel protein test set.

Conclusions

PlasGO, a hierarchical tool incorporating protein language models and BERT, significantly expanded plasmid protein annotations by predicting high-confidence GO terms. These annotations have been compiled into a database, which will serve as a valuable contribution to downstream plasmid analysis and research.
A mixed-methods exploration of the food retail environment of a low-income area of Montevideo, Uruguay
Authors: Ares Gastón , Girona Alejandra , Brunet Gerónimo , Alcaire Florencia , Fajardo Gabriela , Paroli Carolina , Amado Marcelo , Santín Viviana , Vidal Leticia
Published: December 2024

Creating supportive food environments has been identified as one of the most effective strategies to promote healthy diets. In this context, the present work aimed to characterize the retail food environment in a low-income area of the city of Montevideo (Uruguay). The study relied on a mixed-methods approach. A survey of food retail outlets was conducted. All the outlets were geocoded, and service areas were created considering a 600 m threshold. Quantitative information was supplemented with qualitative information from semi-structured interviews with residents and grocery store owners. A total of 415 outlets selling a variety of foods were identified. Adequate physical access to the foods recommended by the Uruguayan dietary guidelines was found in most of the residential areas. Small behind-the-counter grocery stores were identified as the key source of healthy foods in the area. However, the accounts of residents highlighted problems related to the price, variety and quality of the foods sold by the local grocery stores. Therefore, strategies to ensure access to healthy food in the study area should go beyond physical access and tackle food affordability, variety and quality. The promotion of short food supply chains in the area should be a key element of the strategies to achieve sustainable urban food systems in Montevideo.
Trade-offs and complementarities between regional, sectoral, and national support policies for firms’ innovation
Authors: Roper Stephen , Vanino Enrico , Hewitt-Dundas Nola
Published: December 2024

Public support for R&D can play a crucial role in addressing systemic failures that hinder the functioning of innovation systems, whether national, sectoral, or region-specific. However, little is known about the trade-offs and complementarities between subnational and national innovation policies. Here, we consider trade-offs and complementarities between national R&D support measures managed by UK Research and Innovation (UKRI), regional support provided by the Northern Ireland government, and sectoral support provided by the UK’s Catapult network. Using a propensity score matching combined with a difference-in-difference event study analysis, we find evidence of dynamic complementarities between subnational and national innovation policies. Both regional and sectoral innovation support measures have positive effects on both employment and turnover growth. However, each subnational policy targets somewhat different groups of firms to national policy measures. Strong static and dynamic complementarities are also evident between sectoral and national support, as firms initially supported by the Catapults are significantly more likely to secure national R&D funding in the future.
A Geometric Approach to Poincaré Inequality and Minkowski Content of Separating Sets
Authors: Caputo Emanuele , Cavallucci Nicola
Published: December 2024

The goal of this paper is to continue the study of the relation between the Poincaré inequality and the lower bounds of Minkowski content of separating sets, initiated in our previous work [5]. A new shorter proof is provided. It is based on the study of the lower bound of a new geometric quantity, called separating ratio. The main result in this work is the quantitative comparison, in the locally quasigeodesic case, of the infima of the separating ratio and the Minkowski content of separating sets. The proof is based on a novel approach: it uses a new function, called the position function, which allows to fibrate a set in boundaries of separating sets. No Poincaré assumption is needed to prove the main result. We also extend the proof to measure graphs, where due to the combinatorial nature of the problem, the approach is more intuitive. In the appendix, we revise some classical characterizations of the $p$-Poincaré inequality, showing that the equivalences remain true if the several conditions hold only for a fixed couple of points.
On Finite Analogues of Euler’s Constant
Authors: Kaneko Masanobu , Matsusaka Toshiki , Seki Shin-ichiro
Published: December 2024

We introduce and study finite analogues of Euler’s constant in the same setting as finite multiple zeta values. We define a couple of candidate values from the perspectives of a “regularized value of $\zeta (1)$” and of Mascheroni’s and Kluyver’s series expressions of Euler’s constant using Gregory coefficients. Moreover, we reveal that the differences between them always lie in the ${\mathbb{Q}}$-vector space spanned by 1 and values of a finite analogue of logarithm at positive integers.
New Lower Bound on Ball Packing Density in High-Dimensional Hyperbolic Spaces
Authors: Gil Fernández Irene , Kim Jaehoon , Liu Hong , Pikhurko Oleg
Published: December 2024

We present a new lower bound on the Bowen–Radin maximal density of radius-$R$ ball packings in the $m$-dimensional hyperbolic space, improving on the basic covering bound by factor $\Omega (m(R+\ln m))$ as $m$ tends to infinity. This is done by applying the recent theorem of Campos, Jenssen, Michelen, and Sahasrabudhe on independent sets in graphs with sparse neighbourhoods.
Post Quantum Cryptography Explained
Authors: Buchanan Bill
Published: December 2024

Professor Bill Buchanan OBE FRSE considers the impact of advancements in quantum computing on cryptography and explores the methods available for safeguarding data.
NaHCO3 modulates the bla operon and β-lactam susceptibility in borderline oxacillin-resistant Staphylococcus aureus (BORSA)
Authors: Ersoy Selvi C , Madrigal Sabrina L , Proctor Richard A , Chambers Henry F , Xiong Yan Q , Bayer Arnold S
Published: December 2024

Background

Methicillin-resistant Staphylococcus aureus (MRSA) are resistant to nearly all β-lactam antibiotics under standard testing conditions. However, a novel phenotype exists wherein certain MRSA strains exhibit β-lactam susceptibility in the presence of bicarbonate (termed ‘NaHCO3-responsive’), an abundant ion in mammalian tissues and blood. This suggests that specific MRSA infections may be treatable by β-lactams. NaHCO3 responsiveness appears due to effects of NaHCO3 on the expression mecA/PBP2a and other accessory genes required for PBP functionality. mecA expression can be co-regulated by the bla operon regulatory genes, blaI and blaR1.

Objectives

To elucidate the influence of NaHCO3 specifically on the bla operon via investigations of the impact of NaHCO3 on β-lactamase hyper-producing, mecA-negative, borderline oxacillin-resistant Staphylococcus aureus (BORSA) strains.

Methods

Evaluate the effect of NaHCO3 on β-lactam susceptibility via minimum inhibitory concentrations (MIC) assay, expression of genes within the bla operon (blaZ, blaI, blaR1) via RT–qPCR, and β-lactamase (BlaZ) activity via nitrocefinase assay in BORSA.

Results

NaHCO3 enhanced susceptibility to β-lactamase-susceptible β-lactams penicillin and ampicillin. NaHCO3 had no impact on susceptibility to the anti-staphylococcal β-lactams oxacillin and cefazolin, or the anti-MRSA antibiotics vancomycin and daptomycin. NaHCO3 repressed expression of all genes within the bla operon and reduced β-lactamase production.

Conclusions

These data demonstrate that NaHCO3 influences expression of genes within the bla operon, translating to reduced β-lactamase production and enhanced β-lactam susceptibility in BORSA strains. Furthermore, this indicates that the classical blaZ regulators, blaI and blaR1, are the likely mediators of NaHCO3-mediated repression of mecA. However, questions still remain regarding the mechanism via which NaHCO3 regulates the bla operon.
Changes in NNRTI use have not altered the ecology of NNRTI resistance over the last 10 years in people with HIV experiencing virological failure on antiretroviral drugs
Authors: Soulie Cathia , Agher Rachid , Fauchois Antoine , Abdi Basma , Wirden Marc , Teyssou Elisa , Sayon Sophie , Katlama Christine , Valantin Marc-Antoine , Tubiana Roland , Schneider Luminita , Faycal Antoine , Palich Romain , Pourcher Valérie , Marcelin Anne-Geneviève , Calvez Vincent
Published: December 2024

Background

We aimed to determine how non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance profiles have changed over the last decade in people living with HIV (PLWHIV) experiencing virological failure on all antiretroviral treatments, including different NNRTIs.

Materials and methods

We analysed the use of the different NNRTIs in PLWHIV treated with antiretroviral drugs at an academic centre and the HIV NNRTI resistance profiles observed in cases of virological failure over the last 10 years (2014–23). We used the latest ANRS-MIE algorithm (v33; https://hivfrenchresistance.org/) to analyse the resistance mutation profiles of the HIV reverse transcriptase sequences.

Results

During this period, the frequency of NNRTI use remained high, fluctuating slightly between 43.5% (n = 1782/4094) and 39.9% (n = 1758/4421). The use of efavirenz (10.8%–1.5%), nevirapine (7.0%–1.2%), and etravirine (11.0%–1.1%) decreased, whereas the use of rilpivirine (14.7%–26.3%) and doravirine (available from 2018, rising to 9.7% in 2023) increased. These trends were statistically significant for etravirine (P = 0.033) and rilpivirine (P < 0.001). Resistance rates for efavirenz, nevirapine and rilpivirine remained above 15% (efavirenz: 17.3%–16.6%, nevirapine: 16.9%–15.4% and rilpivirine: 17.6%–16.1%). This reflects significant cross-resistance between these three NNRTIs. By contrast, resistance rates were lower for etravirine (7.8%–6.0%) and doravirine (4.9%–4.6%), probably due to differences in their resistance profiles and higher genetic barriers to resistance.

Conclusions

The NNRTI class of antiretroviral drugs remains widely used. Changes in the usage of drugs from this class have not altered the ecology of NNRTI resistance in antiretroviral drug-treated PLWHIV with virological failure during the studied period.
Bacillus safensis LS01 provides biological control of potato common scab with potential effects from secondary metabolites
Authors: Wang Lixue , Liu Song , Liu Lihe , Wang Lichun , Pan Yang , Fu Xuepeng
Published: December 2024

Aims

Potato common scab (CS), caused by pathogenic Streptomyces, is a devastating disease affecting potato crops worldwide. Antagonistic microorganisms have been used as biological control agents to inhibit Streptomyces scabies and reduce the use of synthetic pesticides. However, identifying beneficial microorganisms for controlling CS remains undetermined.

Methods and Results

Strain LS01 was isolated from the geocaulosphere soils of healthy potato tubers. In vitro and pot experiments demonstrated that strain LS01 significantly inhibited the mycelial growth and sporulation of S. scabies, thereby reducing the severity of CS. Sequencing of the 16S rRNA of LS01 indicated that the strain belonged to the species Bacillus safensis. Whole-genome sequencing, metabolomic analysis with liquid chromatograph mass spectrometer, and uultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry analyses indicated that hygromycin B and plantazolicin may be the active secondary metabolites by which B. safensis LS01 inhibits S. scabies.

Conclusions

Bacillus safensis LS01 is a potential biocontrol agent for CS, with its secondary metabolites exerting effective inhibitory effects.
Insights from the timber rattlesnake (Crotalus horridus) genome for MHC gene architecture and evolution in threatened rattlesnakes
Authors: Roseman Marissa A , Mason Andrew J , Bode Emily R , Bolton Peri E , Nachtigall Pedro G , Peterman William E , Gibbs H Lisle
Published: December 2024

Conservation of threatened species can benefit from an evaluation of genes in the major histocompatibility complex (MHC), whose loci encode proteins that bind pathogens and are often under strong selection to maintain diversity in immune response to diseases. Despite this gene family’s importance to disease resistance, little is known about these genes in reptiles including snakes. To address this issue, we assembled and annotated a highly contiguous genome assembly for the timber rattlesnake (Crotalus horridus), a pit viper which is threatened or endangered in parts of its range, and analyzed this new genome along with three other rattlesnake genomes to characterize snake MHC loci. We identified highly duplicated MHC Class I and Class IIβ genes in all species typified by a genomic architecture of discrete gene clusters localized on chromosome 2. The number of loci varied between species from 14 to 23 for MHC I and from 8 to 32 for MHC IIβ and was greater than previously identified in the few non-genome-based studies of reptile MHC to date. We present evidence of the gene family’s complex evolutionary history, with extensive duplication and loss concurrent with speciation resulting in incomplete lineage sorting. The differences in gene number between species combined with a dynamic evolutionary history suggest that gene family expansion/contraction via rapid duplication/gene loss may represent an important mechanism for generating genetic diversity in rattlesnake MHC. Our work demonstrates the utility of whole-genome sequences for identifying functional genetic variation in the form of MHC genes relevant for conservation genomic studies in threatened snakes.
Cell walls: a comparative view of the composition of cell surfaces of plants, algae, and microorganisms
Authors: Fuertes-Rabanal María , Rebaque Diego , Largo-Gosens Asier , Encina Antonio , Mélida Hugo
Published: December 2024

While evolutionary studies indicate that the most ancient groups of organisms on Earth likely descended from a common wall-less ancestor, contemporary organisms lacking a carbohydrate-rich cell surface are exceedingly rare. By developing a cell wall to cover the plasma membrane, cells were able to withstand higher osmotic pressures, colonize new habitats, and develop complex multicellular structures. Thus, the cells of plants, algae, and microorganisms are covered by a cell wall, which can generally be defined as a highly complex structure whose main framework is usually composed of carbohydrates. Rather than static structures, they are highly dynamic and serve a multitude of functions that modulate vital cellular processes, such as growth and interactions with neighbouring cells or the surrounding environment. Thus, despite its vital importance for many groups of life, it is striking that there are few comprehensive studies comparing the cell wall composition of these groups. Thus, the aim of this review was to compare the cell walls of plants with those of algae and microorganisms, paying particular attention to their polysaccharide components. It should be highlighted that, despite the important differences in composition, we have also found numerous common aspects and functionalities.
A simple HPLC method for the determination of plasma progesterone levels in the third trimester of human pregnancy
Authors: Albayrak Mevlut , Kadioglu Yucel , Demirkaya-Miloglu Fatma , Borekci Bunyamin
Published: December 2024

Progesterone is a steroid hormone primarily associated with pregnancy. A simple, rapid, and reliable high-performance liquid chromatography (HPLC) method has been developed and validated for the quantification of progesterone in human plasma. The method consists of a simple liquid-liquid extraction of progesterone and internal standard (estriol) from human plasma using a mixture of hexane and diethyl ether. The chromatographic determination of progesterone was performed using an acetonitrile-water (70:30, v/v) mobile phase with a C18 reversed-phase column. The method achieved an extraction recovery of greater than 96.4% from spiked plasma samples. Intra- and inter-day precision were generally acceptable, with relative SD% less than ≤6.60% and accuracy (relative error %) better than 3.64%. The developed and validated method was used to successfully quantify progesterone levels in plasma samples collected from women during the third trimester of pregnancy. Furthermore, a statistical comparison was conducted between progesterone concentrations in plasma samples obtained from 2 groups of pregnant women: group 1 (n = 9) at 30-35 weeks and group 2 (n = 9) at 36-41 weeks.

The developed and validated HPLC method described in this study enables the successful determination of progesterone in human plasma, offering advantages such as shorter analysis time, simplicity, cost-effectiveness, and potential routine use during pregnancy.
Diagnostic approach for multiple sclerosis: optimizing algorithms for intrathecal synthesis of immunoglobulins
Authors: Ferriz Jorge , Guallart Cristina , Timoneda Pilar , Fandos Marta , Lopez-Arqueros Javier , Sierra-Rivera Antonio , Garcia-Hita Marta , Marcaida Goitzane , Carcelén-Gadea Maria
Published: December 2024

Background

The kappa-free light chain (κFLC) index has shown its value in detecting the intrathecal synthesis of immunoglobulins. We aimed to evaluate the diagnostic performance of the κFLC index for multiple sclerosis (MS) and compare different algorithms proposed in the literature to optimize its use for our population.

Methods

Based on the results of the oligoclonal bands (OCBs) and κFLC index of 255 patients with suspected MS different optimization strategies were evaluated, for which the optimal κFLC index cut-off thresholds were calculated.

Results

The best diagnostic performance was achieved by using a reflexive algorithm, in which OCBs are only performed according to the κFLC index result. With a single cut-off (κFLC index = 7.9), an accuracy of 92.2% was obtained (sensitivity = 92.4%, specificity = 92%) with an OCB performance rate of 58.1%. When applying 2 cut-offs (κFLC index = 4.2 and 13), the accuracy was the same (92.2%, sensitivity = 89.6%, specificity = 94%), but the OCB performance rate dropped to 29.4%.

Conclusion

The 2-step strategy proposed with κFLC determination followed by OCB analysis in the borderline cases appears to be the most suitable solution, further optimized by adjusting the decision thresholds to 4.2 < κFLC index < 13, resulting in high accuracy and the most saving of OCBs.
A combined therapy of meropenem–ZnO nanoparticles efficiently eliminates carbapenem-resistant Klebsiella pneumoniae biofilms, with reduced nephrotoxicity (in vitro)
Authors: Mohamed Alzhraa Ali , Saed Safaa , El-Sayed Sara Ramadan , Yassin Mohamed Taha , Gad Mohamed , Tartour Eman , Fathey Hoda A , Taha Asmaa S , Mohamed Asmaa H , Al-Otibi Fatimah Olyan , AbdelGawwad Mohamed Ragab , Ahmed Mohamed M Sayed , Almalki Susan Ahmed , Abdel-Haleem Mohamed
Published: December 2024

In response to the World Health Organization’s research agenda of antimicrobial resistance in human health, this study appraised the antibacterial and antibiofilm synergistic activity of meropenem and ZnO nanoparticles (ZnO-NPs) combination against carbapenem-resistant Klebsiella pneumoniae (CRKP). The minimum inhibitory concentration (MIC) of meropenem in combination was found to be ~1/12 of its MIC alone. The results of microtiter dilution assay showed that the combination was more efficient in reducing the biofilm biomass than meropenem alone or ZnO-NPs alone. The scanning-electron-microscopy micrographs elucidated that the combination of meropenem with ZnO-NPs has significantly enhanced its competence in eradicating the preformed biofilms of CRKP strains. In addition, the relative gene expression results showed that the combination compared to the meropenem alone and ZnO-NPs alone eloquently down-regulated the expression of biofilm genes (mrkA, fimA, and ecpA). Besides, the MTT-assay demonstrated that the combination has limited cytotoxicity against Vero-cells (in vitro). Overall, this study represents an efficient safe enhancement of meropenem to tackle the growing health threat of CRKP and carbapenem-resistant Enterobacterals prevalence.
Polarized dust emission in Arp220: magnetic fields in the core of an ultraluminous infrared Galaxy
Authors: Clements D L , Zhang Qizhou , Pattle K , Petitpas G , Ding Y , Cairns J
Published: December 2024

Arp 220 is the prototypical ultraluminous infrared Galaxy (ULIRG), and one of the brightest objects in the extragalactic far-infrared sky. It is the result of a merger between two gas rich spiral galaxies which has triggered starbursting activity in the merger nuclear regions. Observations with the submillimeter array centred at a frequency of 345 GHz and with a synthesized beamsize of $0.77\times 0.45$ arcsec were used to search for polarized dust emission from the nuclear regions of Arp 220. Polarized dust emission was clearly detected at 6 $\sigma$ significance associated with the brighter, western nucleus, with a peak polarization fraction of 2.7$\pm 0.35$ per cent somewhat offset from the western nucleus. A suggestive 2.6 $\sigma$ signal is seen from the fainter eastern nucleus. The dust emission polarization is oriented roughly perpendicular to the molecular disc in the western nucleus suggesting that the magnetic field responsible is orientated broadly in the plane of the disc, but may be being reordered by the interaction between the two nuclei. Unlike more evolved interacting systems, we see no indication that the magnetic field is being reordered by the outflow from the western nucleus. These observations are the first detection of dust polarization, and thus of magnetic fields, in the core of a ULIRG.
Circadian Rhythm Mechanisms Underlying Convergent Adaptation of Unihemispheric Slow-Wave Sleep in Marine Mammals
Authors: Yin Daiqing , Yu Zhenpeng , Jiang Haojia , Chong Yujie , Zhong Cuijuan , Xu Shixia , Yang Guang
Published: December 2024

Marine mammals have evolved unihemispheric slow-wave sleep, a unique state during which one cerebral hemisphere sleeps while the other remains awake, to mitigate the fundamental conflict between sleep and wakefulness. However, the underlying mechanisms remain largely unclear. Here, we use a comparative phylogenetic approach to analyze genes associated with light-dependent circadian mechanisms, aiming to reconstruct the evolution of the circadian rhythm pathway in mammals and to identify adaptively changed components likely to have contributed to the development of unihemispheric slow-wave sleep. Specifically, among eight genes with shared signals of positive selection in two unihemispheric slow-wave sleep-specific lineages, seven genes showed direct evidence of affecting sleep and spontaneous movements. Both in vitro and in vivo experiments indicated that functional innovation in cetacean and non-phocid pinniped FBXL21, which was found to undergo positive selection, may be beneficial for decoupling sleep–wake patterns from daily rhythms to sustain continuous swimming. For cetaceans exhibiting only unihemispheric slow-wave sleep, we identified 73 genes as rapidly evolving and 92 genes containing unique amino acid substitutions. Functional assays showed that a cetacean-specific mutation (F411Y) in NFIL3 led to a decrease in repressor activity and protein stability. Furthermore, convergent amino acid replacements detected in genes related to Ca2+ signaling and CREB phosphorylation suggest their crucial role in unihemispheric slow-wave sleep adaptation. Overall, this study enhances our understanding of the evolutionary mechanisms underlying unihemispheric slow-wave sleep and provides a foundation for investigating how circadian rhythm changes contribute to variations in sleep and circadian behavior.
Interaction of N-methylmesoporphyrin IX with a hybrid left-/right-handed G-quadruplex motif from the promoter of the SLC2A1 gene
Authors: Seth Paul , Xing Eric , Hendrickson Andrew D , Li Kevin , Monsen Robert , Chaires Jonathan B , Neidle Stephen , Yatsunyk Liliya A
Published: December 2024

Left-handed G-quadruplexes (LHG4s) belong to a class of recently discovered noncanonical DNA structures under the larger umbrella of G-quadruplex DNAs (G4s). The biological relevance of these structures and their ability to be targeted with classical G4 ligands is underexplored. Here, we explore whether the putative LHG4 DNA sequence from the SLC2A1 oncogene promoter maintains its left-handed characteristics upon addition of nucleotides in the 5′- and 3′-direction from its genomic context. We also investigate whether this sequence interacts with a well-established G4 binder, N-methylmesoporphyrin IX (NMM). We employed biophysical and X-ray structural studies to address these questions. Our results indicate that the sequence d[G(TGG)3TGA(TGG)4] (termed here as SLC) adopts a two-subunit, four-tetrad hybrid left-/right-handed G4 (LH/RHG4) topology. Addition of 5′-G or 5′-GG abolishes the left-handed fold in one subunit, while the addition of 3′-C or 3′-CA maintains the original fold. X-ray crystal structure analyses show that SLC maintains the same hybrid LH/RHG4 fold in the solid state and that NMM stacks onto the right-handed subunit of SLC. NMM binds to SLC with a 1:1 stoichiometry and a moderate-to-tight binding constant of 15 μM−1. This work deepens our understanding of LHG4 structures and their binding with traditional G4 ligands.
The nature of grief: implications for the neurobiology of emotion
Authors: Ratcliffe Matthew , Velasco Pablo Fernandez
Published: December 2024

This paper explores the limitations of neurobiological approaches to human emotional experience, focusing on the case of grief. We propose that grief is neither an episodic emotion nor a longer-term mood but instead a heterogeneous, temporally extended process. A grief process can incorporate all manner of experiences, thoughts, and activities, most or all of which are not grief-specific. Furthermore, its course over time is shaped in various different ways by interpersonal, social, and cultural environments. This poses methodological challenges for any attempt to relate grief to the brain. Grief also illustrates wider limitations of approaches that conceive of emotions as brief episodes, abstracted from the dynamic, holistic, longer-term organization of human emotional life.
Week 96 Results of Bictegravir/Emtricitabine/Tenofovir Alafenamide for HIV Treatment in People With Substance Use Disorders
Authors: Havens Joshua P , Bares Sara H , Lyden Elizabeth , Fadul Nada , Swindells Susan
Published: December 2024

Background

The BASE study (NCT03998176), a phase 4, 48-week (W), single-arm, prospective trial, revealed that the use of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV and substance use disorders (PWH/SUD) was safe and effective without emergent antiretroviral resistance despite incomplete adherence. Here, we present the W96 results.

Methods

A retrospective analysis of all participants enrolled in the BASE study was completed from W48 to W96. End points of interest at W96 included the proportion of participants with viral suppression (VS; HIV RNA <50 copies/mL [c/mL]), incidence of protocol-defined virologic failure (PDVF; 2 consecutive ≥400 c/mL), safety, adherence (percentage of days covered [PDC]), retention in care, and prevalence of ongoing substance use.

Results

All enrolled BASE participants (n = 43) were included in the W96 analysis. At W48, 21 participants (49%) had achieved VS (intent-to-treat [ITT]). Thirty-six (84%) participants completed W96, with 19 achieving an HIV RNA <50 copies/mL (ITT, 44%; per-protocol, 54%). Seven participants (19%) met PDVF; genotyping was performed on 2, with no evidence of treatment-emergent antiretroviral resistance noted. No safety signals were identified or attributed to B/F/TAF. Adherence to B/F/TAF decreased 18% after W48 (mean PDC: W0–W48, 72%; W48–W96, 54%; P < .01). Participants exhibiting adherence rates of ≥4 doses/wk (PDC ≥57%) were more likely to achieve VS (PDC ≥57%, 84.2%, vs PDC <57%, 15.8%; P < .01). Retention in care remained stable, and participants continued to use substances through W96.

Conclusions

At W96, the proportion of PWH/SUD achieving VS with B/F/TAF decreased to 44%, along with an adherence decrease of 18%, with no evidence of treatment-emergent HIV drug resistance occurring.
The Economic Burden of Herpes Zoster in Individuals Aged 50 Years or Older and Those With Underlying Conditions in Italy
Authors: Zarkadoulas Eleftherios , Comparoni Simona , Freguja Riccardo , Santacroce Roberto , Dovizio Melania , Veronesi Chiara , Degli Esposti Luca , Gentile Ivan , Bonanni Paolo , Rossi Alessandro
Published: December 2024

Background

Risk of herpes zoster (HZ) infection increases with age and immunosuppression. We estimated the impact of HZ and post-herpetic neuralgia (PHN) on direct costs and health care resource utilization (HCRU) in patients ≥50 years, including those with comorbidities, as limited information exists in Italy.

Methods

This retrospective analysis used reimbursement data from local health authorities in Italy (January 2009–June 2022). Cases of HZ and PHN identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes and drug prescriptions were characterized and followed up for 1 year before and after the index date. The direct HCRU costs for patients with HZ/PHN were compared with those for patients without HZ/PHN.

Results

Of the total 193 259 patients with HZ/PHN identified (mean age, 61.6 years), 145 923 were ≥50 years old (immunocompromised: 29.9%; ≥1 chronic condition: 76.1%). During follow-up, 18.8% of patients ≥50 years of age with HZ progressed to PHN complications, and 3618 hospital admissions were reported (median length of stay, 9 days). Drug prescriptions and all-cause hospitalizations were the main contributors to total annual direct health care costs, estimated at M€272 for patients with HZ/PHN, whose burden increased with age. Higher health care costs were observed in patients with HZ/PHN vs patients without HZ/PHN. Moreover, average health care costs were up to 4× higher for patients with HZ and PHN compared with those without PHN.

Conclusions

HZ causes a significant economic impact on the health care system, driven mainly by high costs of medications and hospitalizations among older adults and those with comorbidities, particularly when complicated by PHN.
Weight loss in patients on osimertinib for metastatic EGFR-mutant non-small cell lung cancer
Authors: Chen Lanyi Nora , Ma Xin , Herzberg Benjamin , Henick Brian S , Biswas Anup K , Acharyya Swarnali , Shu Catherine A
Published: December 2024

Background

Cachexia is characterized by weight loss and decline in muscle mass and function and is a poor prognostic factor among patients with cancer. Patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC) derive remarkable survival benefits with osimertinib, a third-generation EGFR tyrosine kinase inhibitor. It is not known whether patients treated with osimertinib experience any weight loss or whether weight loss impacts patient outcomes. Therefore, we sought to describe the frequency and consequences of weight loss in this patient population.

Materials and methods

We conducted a single-center retrospective pilot study of 56 patients treated with first-line osimertinib for metastatic EGFR-mutant NSCLC. We defined on-treatment weight loss as a loss of ≥5% body weight at 6 or 12 months of treatment. We described the characteristics of patients with and without on-treatment weight loss and differences in progression-free survival (PFS), time on treatment with osimertinib, and overall survival (OS).

Results

Forty-six percent (n = 26) of patients met the criteria for on-treatment weight loss. There were no significant differences in patient or disease characteristics between patients with and without weight loss. Compared to patients without weight loss, patients with weight loss had similar PFS and time on treatment with osimertinib. Yet, patients with weight loss had significantly worse overall survival (HR 4.91, 95% CI, 1.56-15.5, P = .007).

Conclusion

Weight loss was observed in nearly half of patients with metastatic EGFR-mutant NSCLC treated with osimertinib, and patients with weight loss had significantly worse overall survival.
Macroevolution of body extremities reveals an integrated phenotypic response of coloration and morphology to temperature in a large clade of Neotropical passerines (Furnariida)
Authors: Macedo Gabriel , Marcondes Rafael S , Bravo Gustavo A , Derryberry Elizabeth P , Biondo Cibele
Published: December 2024

Endotherms show smaller extremities (Allen’s rule) and larger body sizes (Bergmann’s rule) in colder climates, thereby reducing heat loss. Coloration can also be important in thermoregulation, as darker coloration absorbs more radiant energy than lighter coloration (Bogert’s rule or thermal melanism hypothesis). Extremities lacking or bearing thinner covers of feathers or fur—such as ears, legs and bills—can be important thermal windows to exchange heat. Yet, no study to date has simultaneously investigated the coloration and morphology of body extremities in relation to temperature. In 566 species of Furnariida (Neotropical ovenbirds and allies), we tested with phylogenetic comparative methods whether body extremity coloration, morphology and plumage coloration jointly respond to temperature. We predicted that, in colder climates, bills and tarsi would be darker and smaller as well as associated with darker plumage and larger body sizes. Consistent with this prediction, we found that bills are darker, smaller and are associated with darker plumage and larger body sizes in colder climates. Tarsi are darker and associated with darker plumage and larger body sizes in colder climates, but tarsus coloration is not associated with tarsus length, which, contrary to predictions of Allen’s rule, was longer in colder climates. Using phylogenetic path analyses, we found that climate affects body extremity coloration both directly and indirectly through its effects on habitat type, plumage coloration, and morphology. Our study suggests that temperature promotes an integrated phenotypic response of coloration and morphology across body extremities, plumage, and body size.
A review on recent progress in synthesis, properties, and applications of MXenes
Authors: Borah Ashish Jyoti , Natu Varun , Biswas Abhijit , Srivastava Anchal
Published: December 2024

MXenes, a noble class of two-dimensional (2D) material, discovered in 2011 have gained attention in recent years. They have attracted significant attention due to their flexible elemental composition, distinctive 2D-layered architecture, large surface area, and abundant surface terminations. Top-down synthesis techniques such as HF etching, alkaline etching, and electrochemical methods are used for MXene synthesis. Alongside these methods, methods like chemical vapor deposition (CVD), template method and plasma enhanced pulsed layer deposition (PELPD) are also used for the thin-film synthesis of MXenes. The discovery of double transition-metal layered MXene, solid, and high entropy MXene open up the prospect of further novel structures. MXenes are electrically conductive and have promising optoelectronic, mechanical, and thermoelectric properties. MXenes have also shown immense potential in biomedicine and environmental applications. The surface chemistry of MXene make them ideal for biosensors, drug delivery, and photothermal therapy, while their photocatalytic and adsorption properties enable efficient removal of pollutants and contaminants from water. This review examines the various MAX phase synthesis methods, such as solid-state reactions, hot isostatic pressing, and spark plasma sintering, followed by top-down techniques like HF etching, alkaline etching, and electrochemical etching, as well as bottom-up methods like CVD, template approaches, and plasma-enhanced pulsed layer deposition. The review also looks into the optical, chemical, and electronic properties of MXene, as well as their advancements in energy storage, optoelectronics, pollution avoidance, biomedical applications, and more.
Phase separation of MYB73 regulates seed oil biosynthesis in Arabidopsis
Authors: Yang Yuzhou , Kong Que , Ma Zhiming , Lim Peng Ken , Singh Sanjay K , Pattanaik Sitakanta , Mutwil Marek , Miao Yansong , Yuan Ling , Ma Wei
Published: December 2024

MYB family transcription factors (TFs) play crucial roles in plant development, metabolism, and responses to various stresses. However, whether MYB TFs are involved in regulating fatty acid biosynthesis in seeds remains largely elusive. Here, we demonstrated that transgenic Arabidopsis (Arabidopsis thaliana) plants overexpressing MYB73 exhibit altered FATTY ACID ELONGATION1 (FAE1) expression, seed oil content, and seed fatty acid composition. Electrophoretic mobility shift assays showed that FAE1 is a direct target of MYB73, and functional assays revealed that MYB73 represses FAE1 promoter activity. Transcriptomic analysis of the MYB73-overexpressing plants detected significant changes in the expression of genes involved in fatty acid biosynthesis and triacylglycerol assembly. Furthermore, MYB73 expression was responsive to abscisic acid (ABA), and ABA-responsive element binding factor 2 directly bound to the ABA-responsive element in the MYB73 promoter to activate its expression. Additionally, we determined that MYB73 exhibits the hallmarks of an intrinsically disordered protein and forms phase-separated condensates with liquid-like characteristics, which are important in regulating target gene expression. Together, our findings suggest that MYB73 condensate formation likely fine-tunes seed oil biosynthesis.