bluuebunny/crossref_metadata_2025 huggingface dataset:
Artifacts Removal from Multi-mode Dispersion Image: New Imaging Conditions of Beamforming and Random Array
Authors: Qin Tongwei , Lu Laiyu
Published: February 2025

Beamforming (BF) has been demonstrated to extract multi-mode surface wave dispersion curves from ambient seismic noise. However, due to the limited sampling of the array and the complex distribution of the noise sources, the dispersion image generated by the array-based technique is usually contaminated by aliasing or artifacts. According to seismic interferometry (SI) theory, the Green's function (GF) in the time domain can be retrieved using the noise cross-correlation function (NCF). The Fourier transform of NCFs, i.e. the spatial coherence function, is related to the imaginary part of the frequency domain GF. For the vertical component of the surface wave, it corresponds to the zero-order Bessel function of the first kind, i.e. the standing wave containing propagating waves in two directions described by positive and negative vector wavenumber. In array techniques based on wavefield transforms, it is common to adopt the propagating wave instead of the standing wave to eliminate the aliasing associated with the negative wavenumber, i.e. to replace the Bessel function using the Hankel function or to construct a complete GF via the Hilbert transform. In this paper, we quantitatively analyze the characteristics of three types of aliasing, i.e. the aliasing associated with the period extension of the positive wavenumber, the aliasing associated with the negative wavenumber and those associated with the constant wavenumber. The theoretical representations of different imaging conditions are derived for the finite sampling of the wavefield. A new BF imaging condition is then proposed to remove the crossed artifacts, a type of aliasing associated with the negative wavenumber. The new imaging condition relies only on the computed NCFs and does not require reconstruction of the complete GF via the Hilbert transform. The advantage of random sampling in removing artifacts is illustrated. A random array design scheme is suggested by investigating the array performance of the random array and the array designed using tiles of the Hat family newly discovered in the field of monotile aperiodic tiling. We show the artifacts associated with the constant wavenumber, which are usually manifested as a straight line in the dispersion image of the frequency-velocity domain, also known as radial artifacts, can be eliminated by windowing the NCFs.
Mapping commercial practices of the pesticide industry to shape science and policymaking: a scoping review
Authors: Schölin Lisa , Petticrew Mark , Collin Jeff , Knipe Duleeka , Barry Rachel , Eddleston Michael , Gunnell David , Pearson Melissa , van Schalkwyk May C I
Published: February 2025

There is a growing body of evidence for how health harming industries (HHIs) engage in similar practices to influence science and policymaking. However, limited attention has been paid to the pesticide industry within the commercial determinants of health (CDOH) field. We conducted a scoping review to map practices adopted by the pesticide industry to influence science and policymaking and to assess the breadth and focus of the associated literature. We included 31 documents and categorized the extracted data using a typology of commercial practices. The documents described how major pesticide companies, and their trade bodies, have acted to influence science and maintain favourable regulatory environments while undermining the credibility of researchers and agencies that publish findings threatening to their commercial interests. A large proportion of the literature consists of historical analyses, narrative reviews, commentaries/perspective pieces, and investigative reports published in the grey literature, predominantly informed by analysis of internal industry documents and freedom of information requests. Most studies focus on high-income settings. There were a limited number of primary peer-reviewed empirical studies that explicitly aimed to study the practices of the pesticide industry from a CDOH perspective. However, our findings show that major pesticide companies adopt political and scientific practices highly similar to other HHIs. The review shows a critical need for research on the pesticide industry’s current practices in low- and middle-income countries where the negative impacts of its activities on health and the environment are likely to be more marked.
The bacterial quality and safety of cold smoked salmon during production and subsequent chilled storage
Authors: Maughan Léon , Whyte Paul , Bolton Declan
Published: February 2025

Aim

This study aimed to investigate the bacteriology of cold smoked salmon (CSS), specifically changes in the bacterial quality (total viable count (TVC) and total Enterobacteriaceae count (TEC)), the concentration of spoilage bacteria (lactic acid bacteria (LAB), hydrogen sulphide producing bacteria (HSPB) and Pseudomonas spp.) and Listeria monocytogenes during salting, washing, smoking, maturation, packaging and chilled storage.

Methods and results

In-plant and laboratory based studies were undertaken. The salt concentration, pH and aw of the commercial product were 3.8% (w/w), 5.9 and 0.95, respectively while those of the laboratory prepared CSS were 1.1%, 6.2 and 0.94. Although the CSS preparation process enhanced microbial quality, as determined by significant (p < 0.05) reductions in indicator and spoilage bacterial counts, L. monocytogenes was unaffected and all bacteria showed significant (p < 0.05) growth during chilled storage of the final product.

Conclusions

The microbial quality and safety of CSS is reliant on using uncontaminated fillets, good hygiene practices and ensuring that the shelf-life does not afford L. monocytogenes sufficient time to exceed the 100 cfu g−1 maximum allowed in current EU legislation (EC 2073/2005).
Investigation of the nutritional and functional roles of a microencapsulated blend of botanicals on intestinal health and growth of nursery pigs challenged with F18+ Escherichia coli
Authors: Garavito-Duarte Yesid , Bonetti Andrea , Tugnoli Benedetta , Choi Hyunjun , Piva Andrea , Grilli Ester , Kim Sung Woo
Published: February 2025

The study aimed to evaluate the effects of increasing levels of a microencapsulated blend of botanicals (MBB) on the intestinal health and growth performance of nursery pigs challenged with F18+  E. coli. Sixty-four nursery pigs (6.8 ± 0.3 kg) were assigned to four dietary treatments in a randomized complete block design, with initial body weight and sex as blocks, and fed for 28 d in 3 phases. Treatments were a basal diet fed to pigs without F18+  E. coli challenge (NC) and 3 levels of MBB (0.0, 0.1, and 0.2%) in pigs challenged with F18+  E. coli. On d 7 of the study, pigs in challenged group were orally inoculated with F18+  E. coli (1.5 × 1010 CFU). On d 7 and 21 post-challenge, pigs were euthanized to collect jejunal tissues and mucosa. Compared to the NC, 0.0% MBB increased (P < 0.05) relative abundance (RA) of Staphylococcus saprophyticus and reduced (P < 0.05) Streptococcus parasuis at d 7 and 21 post-challenge, respectively. Increasing levels of MBB decreased (linear: P < 0.05) RA of Staphylococcus saprophyticus on d 7 post-challenge. Compared to the NC, 0.0% MBB increased (P < 0.05) jejunal NOD2 and IL-6 expression and decreased (P < 0.05) ZO-1 on d 7 post-challenge. Compared to the NC, 0.0% MBB decreased (P < 0.05) jejunal IL-6, IL-8, and TNF-α and increased (P < 0.05) IgG on d 21 post-challenge. Increasing levels of MBB increased OCLN (linear: P < 0.05) and ZO-1 (linear and quadratic: P < 0.05) on d 7 post-challenge and decreased TLR4 (linear and quadratic: P < 0.05). Compared to the NC, 0.0% MBB decreased (P < 0.05) Ki-67+ on d 7 post-challenge. Increasing levels of MBB increased (linear: P < 0.05) Ki-67+ on d 7 post-challenge and VH:CD on d 21 post-challenge. In overall period, compared to the NC, 0.0% MBB decreased (P < 0.05) average daily gain. Increasing daily MBB intake linearly increased OCLN on d 7 and VH:CD on d 21, and reduced TLR4 and IL-8 on d 21 post-challenge, but exhibiting quadratic effects (P < 0.05) on ZO-1 (optimal at 0.12% of MBB), IgG (optimal at 0.14% of MBB), and G:F during d 7 to 20 and d 7 to 28 (optimal at 0.22% and 0.10% of MBB, respectively). In conclusion, F18+  E. coli challenge negatively modulated the jejunal mucosal microbiota and reduced intestinal morphology and growth of nursery pigs. Supplementation of MBB at 0.10 to 0.14% provided optimal mitigation of the impacts of F18+  E. coli challenge on humoral immunity, intestinal integrity, jejunal morphology, and feed efficiency of pigs.
Development of a dried blood spot screening test using gas chromatography coupled to high-resolution mass spectrometry: application in authentic postmortem samples
Authors: Dubois-Chabert D , Flament E , Hoizey G , Chatenay C , Fanton L , Bottinelli C
Published: February 2025

Objective: To develop a toxicological screening analysis using gas chromatography coupled with high-resolution mass spectrometry (GC-HRMS) on postmortem dried blood spots (DBSs), and apply it to authentic cases.

Method: Twenty-five µL of blood was deposited and dried on a paper card. Compounds of interest were desorbed, extracted and acetylated, then injected into the GC-HRMS. The limits of detection (LOD) and of identification (LOI) were determined for 22 of the compounds most frequently detected in postmortem blood samples in the laboratory in 2022.Stability on DBS was studied at 3 temperatures (-20°C, +4°C, and +20°C) over 15 days. The method was then applied to 102 postmortem blood samples. Results were compared to the two conventional screening methods implemented in the laboratory: LC-DAD/MS and GC-MS.

Results: Selectivity was demonstrated by analysis of 10 negative postmortem blood samples. All LODs were between <10.0 ng/mL and 20.0 ng/mL. LOIs were within the therapeutic concentration range for each compound or at a value not leading to acute intoxication (narcotics). Overall, compounds remained stable over the 15 days at all test temperatures, except for midazolam and tramadol and its metabolites. Comparison of screenings of 102 postmortem samples resulted in 239 identifications, corresponding to 74 compounds, across 70 positive cases. In 32 cases, no compound was identified. Respectively 57% and 60% of the compounds were detected by LC-DAD/MS and GC-MS screenings, while DBS-GC-HRMS identified 81%.

Discussion-Conclusion: Application of the method to a hundred authentic cases demonstrated its ability to meet the constraints of low sample volume, sensitivity and ease of preservation for urgent cases or cases with limited blood availability.
Identification of In Vivo and In Vitro Metabolites of Fentanyl Using UHPLC-Q-Orbitrap-HRMS
Authors: Liu Meng , Zhao Sen , Wang Bin-jie , Zhou Hong , Liu Yao
Published: February 2025

A comparative analysis of the metabolites and metabolic pathways of fentanyl was conducted in liver microsomes and zebrafish models utilizing ultra-high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). A total of 21 metabolites were identified across both liver microsomes and zebrafish models. These included 9 phase I metabolites, such as N-dealkylated, N-oxidated and hydroxylated products, and 12 phase II metabolites, including glucuronidated, methylated, and sulfated products, as well as a series of products derived from conjugation with glutathione. Notably, the products derived from conjugation with glutathione are reported here for the first time. This study provides a comprehensive and in-depth comparative analysis of fentanyl metabolism in liver microsomes and zebrafish, offering a foundation for analyzing and identifying biological samples in cases of fentanyl misuse and fatalities.
Prevention of glucocorticoid-induced impairment of bone metabolism – a randomized, placebo-controlled, single Centre proof-of-concept clinical trial
Authors: Gregori Giulia , Johansson Lisa , Silberberg Lena , Imberg Henrik , Magnusson Per , Lind Marcus , Lorentzon Mattias
Published: February 2025

Oral glucocorticoid (GC) therapy rapidly and deleteriously affects bone metabolism and blood glucose regulation. The gut microbiota regulates bone metabolism and a prior study found that Limosilactobacillus reuteri ATCC PTA6475 (L.reuteri) reduced bone loss over 12 months in older women. Mice treated either with broad-spectrum antibiotics or with L.reuteri did not experience GC-induced trabecular bone loss. This proof-of-concept, randomized, double-blind, placebo-controlled trial aimed to investigate if daily supplementation with L.reuteri, compared to placebo, could mitigate or prevent the negative effects of oral GC on bone turnover and blood glucose regulation in healthy young adults. Twenty-one men and 29 women, aged 18–45 were randomized to either placebo or L.reuteri (1x1010CFU/day) treatment for two weeks, followed by open-label oral prednisolone 25 mg daily for seven days. Primary outcomes were changes in blood bone status indices (osteocalcin, C-terminal telopeptide cross-links of collagen type-I (CTX), and type-I procollagen intact N-terminal propeptide (PINP)) from baseline to seven days after starting oral GC. Secondary endpoints included changes in blood glucose levels using continuous glucose monitoring (CGM) during the same period (ClinicalTrials.gov NCT04767711). Blood samples were collected from participants in the morning after overnight fasting. Forty-six participants completed the 30-day study. The L.reuteri and placebo groups were well balanced in terms of baseline characteristics (age, BMI, sex, dietary intake, and physical activity). No significant differences were found between L.reuteri vs. placebo for percent changes in CTX (-0.3 [95%CI -19.2–18.7], p=.98) or PINP (4.2 [-6.3–14.8], p=.43), or in osteocalcin levels (14.2 [-7.8–36.3], p=.21), although the group-to-group difference in osteocalcin was larger. There was no effect of treatment on mean blood glucose (-0.1 [-0.3–0.1] mmol/L, p=.28). In conclusion, we failed to detect a significant effect of L.reuteri supplementation on GC-related adverse effects on bone status indices in this proof-of-concept RCT. Larger studies are needed to identify any potential smaller effects.
General and individualized changes in T cell immunity during aging
Authors: Song Nianbin , Elbahnasawy Mostafa A , Weng Nan-Ping
Published: February 2025

Functional alterations with age are observed in all human systems, but the aging of the adaptive immune system displays both general changes affecting all individuals, and idiosyncratic changes that are unique to individuals. In the T cell compartment, general aging manifests in three ways: (1) the reduction of naïve T cells, (2) the accumulation of differentiated memory T cells, and (3) a reduced overall T cell receptor (TCR) repertoire. Idiosyncratic impacts of aging, such as changes in the TCR repertoires of altered memory and naïve T cells are shaped by each person’s life exposures. Recent advancements in single-cell sequencing provide new information including the identification of new subpopulations of T cells, characteristics of transcriptome changes in T cells and their TCR clonotype with age, and measurement of individual cell age. Here, we focus on the changes in T cell subpopulations, transcriptomes and TCR repertoires in overall and antigen-specific T cell population with aging.
Pupil plane intensity interferometry with imaging air cherenkov telescopes
Authors: Matthews N , Gori P M , Vakili F
Published: February 2025

The Intensity Interferometry Imaging Telescope (I3T) concept illustrated how a single imaging air Cherenkov telescope (IACT) can be transformed into a multi-element intensity interferometer. This is achieved by segmenting the light collecting surface into many sub-apertures via active control of individual mirror facets. Here, we propose an alternative method applicable to all IACTs that we refer to as pupil plane intensity interferometry. Principally, the re-imaged pupil of an IACT can be subdivided with a multi-pixel detector to enable extremely dense uv-plane sampling. Ray tracing of an IACT based on one of the VERITAS telescopes was performed as a proof-of-principle. Several unique science cases could be investigated and, in particular, we performed a case study that indicates the ability to strongly constrain the angular brightness distribution of the extended disc of the Be star Gamma Cassiopeia. The proposed design could be used as an alternative to current intensity interferometry instruments as it mitigates several inherent limitations of IACTs when used as intensity interferometers, namely temporal dispersion and large angular point spread functions.
A jet-driven bipolar outflow in NGC 1125
Authors: Schönell Astor J , Riffel Rogemar A , Riffel Rogério , Storchi-Bergmann Thaisa
Published: February 2025

To study the role of the feedback from the Active Galactic Nuclei (AGNs) in the evolution of its host galaxy, we need observational constraints on 100 pc scales. We used the Gemini Near Infrared Integral Field Spectrograph in the J and K bands at a spatial resolution of 100 pc and spectral resolution of 45 km s−1 to observe the central region of the Seyfert galaxy NGC1125. Emission-line flux distributions in ionized and molecular gas extends up to ≈ 300 pc from the nucleus, where they are found to peak. The Paβ and [Fe ii]λ1.2570μm emission-lines show two components: a narrow and a broad. The narrow component is preferably extended from the north-east to the south-west, while the broad component is perpendicular to it. Their kinematics are also different, with the narrow component showing a rotation pattern, with low velocity dispersion values (σ ≈ 140 km s−1) and the broad component a disturbed velocity field and high values of σ (≈ 250 km s−1). We interpreted the narrow component velocity fields as due to gas rotating in the galaxy plane and fitted rotation velocity models to it, plus an outflow component in the ionized gas. The broad component is interpreted as an outflow, with mass outflow rate in the range of 0.6 to 1.1 M⊙ yr−1, with an outflow power ranging from 3.9× 1040 to 1.1× 1041 erg s−1, which represents 0.07 % and 0.2 % of the bolometric luminosity of the AGN. There is an explicit relation between the shock ionized outflow and the low-luminosity radio source.
The long life of ultra diffuse galaxies inside low-density dark matter halos: the case of AGC 114905
Authors: Afruni Andrea , Marinacci Federico , Piña Pavel E Mancera , Fraternali Filippo
Published: February 2025

It has long been known that, in the absence of a dark matter (DM) halo, galaxy discs tend to develop global gravitational instabilities that strongly modify their initial structure. The recent discovery of gas-rich ultra diffuse galaxies (UDGs) that seem to live in DM halos with very low concentrations, a very atypical configuration in the standard cosmological framework, poses therefore a crucial question: is the small contribution from such DM halos sufficient to stabilize the UDG discs? In this work we investigate this question, focusing on the extreme UDG $\rm {AGC\ 114905}$, which previous works found to be unstable. Here, we revisit these studies, using idealised numerical simulations with AREPO of a system composed by a stellar disc, a gas disc and a DM halo in initial equilibrium with each other and with properties based on slightly revised observational data of $\rm {AGC\ 114905}$. We explore different scenarios for the DM halo and we run our simulations for 5 Gyr. We find that in all cases the stellar and the gas discs are stable and that their initial density distributions and kinematic properties remain unchanged during the course of the simulation. We discuss how the apparent discrepancy with previous works (where the UDG developed instabilities) is due to our discs being dynamically hotter and living in slightly more massive DM halos, in accordance with the new observational constraints, previously unavailable. Our findings demonstrate that $\rm {AGC\ 114905}$ (and likely other similar UDGs) can evolve unperturbed in halos that challenge current cosmological models.
Recovering the structure of debris disks non-parametrically from images
Authors: Han Yinuo , Wyatt Mark C , Marino Sebastian
Published: February 2025

Debris disks common around Sun-like stars carry dynamical imprints in their structure that are key to understanding the formation and evolution history of planetary systems. In this paper, we extend an algorithm (rave) originally developed to model edge-on disks to be applicable to disks at all inclinations. The updated algorithm allows for non-parametric recovery of the underlying (i.e., deconvolved) radial profile and vertical height of optically thin, axisymmetric disks imaged in either thermal emission or scattered light. Application to simulated images demonstrates that the de-projection and deconvolution performance allows for accurate recovery of features comparable to or larger than the beam or PSF size, with realistic uncertainties that are independent of model assumptions. We apply our method to recover the radial profile and vertical height of a sample of 18 inclined debris disks observed with ALMA. Our recovered structures largely agree with those fitted with an alternative visibility-space de-projection and deconvolution method (frank). We find that for disks in the sample with a well-defined main belt, the belt radius, fractional width and fractional outer edge width all tend to increase with age, but do not correlate in a clear or monotonic way with dust mass or stellar temperature. In contrast, the scale height aspect ratio does not strongly correlate with age, but broadly increases with stellar temperature. These trends could reflect a combination of intrinsic collisional evolution in the disk and the interaction of perturbing planets with the disk’s own gravity.
The proteomic landscape of diffuse midline glioma highlights the therapeutic potential of non-histone protein methyltransferases
Authors: Anguraj Vadivel Arun Kumaran , Pajovic Sanja , Siddaway Robert , Zhu Sabrina , Sbergio Stefanie-Grace , Matic Olivera , Phillips Lauren , Bu Yong Jia , Nitz Mark , Hawkins Cynthia
Published: February 2025

Background

Diffuse Midline Glioma (DMG) is a highly aggressive pediatric brain tumor with limited treatment options despite extensive genomic characterization. The aim of this study was to investigate the proteomic landscape of DMG to identify potential therapeutic targets.

Methods

We conducted a comprehensive proteomic analysis using LC-MS3, along with DNA methylation and DNA/RNA sequencing in 55 DMG patients’ samples. PTM profiling (phosphoproteome and methylproteome) was conducted in 30 patient samples. We then investigated the effects of modulating key protein targets on protein methylation, protein synthesis, and DMG cell growth in vitro and in vivo.

Results

DMGs exhibited high global protein methylation, with significant enrichment of translation machinery proteins and factors involved in apoptosis regulation. Surprisingly, while targets of key kinases were highly phosphorylated, overall protein phosphorylation was lower in DMG compared to normal brain tissues. Non-histone methyltransferases METTL13 and METTL21B, along with protein kinases PAK2, PRKACA, and AKT1, were identified as key players in DMG methylproteome and phosphoproteome, respectively. METTL13 knockdown led to reduced EEF1A1 protein methylation, a shift in oncoprotein synthesis, and inhibited DMG cell growth in vitro and in vivo.

Conclusions

Our findings highlight the dependency of DMG on methyl-signaling pathways, particularly involving METTL13, which regulates EEF1A1 protein methylation and oncoprotein synthesis. Targeting the non-histone methyltransferases offers a promising therapeutic strategy for DMG. This study underscores the potential of post-translational modifications, specifically methyl-signaling pathways, as novel therapeutic targets for DMG and possibly other currently incurable cancers.
Investigating the Origins of Status Threat among White Americans
Authors: Lindsay Spencer C , Melcher Cody R
Published: February 2025

In the last decade and a half, the United States has seen a rise in right-wing nationalism. Status threat provides a compelling explanation as to why. As white Americans see changing demographics, more diverse imagery in American leadership, and increased interdependence globally, they fear that they are losing “their” country. Scholars, however, often see status threat as primarily symbolic rather than material. We argue that material concerns are also instrumental in shaping whites’ perception of status threat. We test this hypothesis using an original survey experiment in which some respondents are primed to think about symbolic or material aspects of status threat. Relative to the control, both groups express heightened levels of perceived threat from other groups, indicating that both material and symbolic concerns are instrumental in shaping perceptions of status threat. We additionally test whether Republican whites respond to this perceived threat by becoming more likely to endorse far-right, restrictionist immigration policies. Our findings on the latter question are mixed.
Blame Attribution, Partisanship, and Federalism: Evidence from a Panel Survey
Authors: Uttermark Matthew J , Mewhirter Jack , Sanders Rebecca , McLaughlin Danielle M
Published: February 2025

When disaster strikes in federal systems, who do citizens blame and why? Partisan blame attribution (PBA) suggests that Republicans and Democrats hold consistent ideological preferences on which level of government should respond and receive blame for policy failures in times of crisis. Conversely, partisan federalism (PF) suggests that partisans will opportunistically assign blame to the level of government controlled by their disfavored party. Research on blame attribution has yet to assess which mechanism better explains patterns of blame attribution among individuals. We test each mechanism to evaluate patterns of blame attribution related to the COVID-19 pandemic. Leveraging panel survey data collected before the 2020 election and after the 2021 presidential transition, we find that Democrats uniformly follow PF expectations, whereas Republicans follow both PBA and PF expectations. We conclude that scholars should revisit blame attribution and more carefully consider the role of federalism in determining citizen preferences.
The Rhetorical “What Goes with What”: Political Pundits and the Discursive Superstructure of Ideology in US Politics
Authors: Green Jon
Published: February 2025

In his foundational essay, Philip Converse (1964) alludes to a small class of political sophisticates who are influential in the social construction and diffusion of ideological belief systems. However, despite their importance to the nature of ideology in the public at large, there is little empirical research focusing on those select few involved in this process of “creative synthesis”—and work examining the rhetorical structures that cohere sets of plausibly independent issue stances is rarer still. I do so here using a novel dataset of tweets sent by roughly 1,000 of the most prominent political pundits in the United States from January through August of 2019. Using a combination of text and network-analytic techniques, I identify robust relationships between both how pundits discuss a wide range of political concepts and the extent to which this discussion is informative of their network-based preferences. I find that broad, organizing concepts such as partisan and ideological labels emerge as central in political discourse, facilitating indirect links between a wide range of issues. However, I also find that discussions of discrete policy issues and political concepts are highly informative of pundits’ latent preferences. This descriptive account of the discursive superstructure of ideology offers new evidence regarding how creative synthesis is conducted in practice.
Potential drug interactions with nirmatrelvir/ritonavir in critically ill patients with COVID-19 – a retrospective observational study
Authors: Jarczak Dominik , König Christina , Röhr Anka C , Forstreuter Anika , Brehm Thomas Theo , Schulze zur Wiesch Julian , Roedl Kevin , Kluge Stefan , Fischer Marlene
Published: February 2025

Objectives

Nirmatrelvir/ritonavir is recommended for high-risk patients with COVID-19 to reduce disease progression and mortality. Ritonavir significantly increases the bioavailability of nirmatrelvir and is the most potent irreversible cytochrome P 450 3A4 inhibitor in clinical use, resulting in a substantial risk for drug-drug interactions (DDI). We aimed to analyze the incidence of potential DDI (pDDI) in critically ill patients with SARS-CoV-2 infection.

Methods

This is a retrospective single-center study in a quaternary care center in Northern Germany. We reviewed electronic health records for demographic characteristics, comorbid conditions, and medication history. The pre-existing comedication was screened for pDDI with nirmatrelvir/ritonavir using publicly available databases. Binary logistic regression was used to identify patient characteristics associated with pDDI.

Key Findings

Of 500 critically ill patients with SARS-CoV-2 infection, 362 (72.4%) received pre-existing comedication. A total of 241/500 patients (48.2%) had a medication history prone to pDDI. Antidiabetics, lipid-lowering drugs, and anticoagulants were among the most frequently used agents with a pDDI. Higher age (OR 1.043; 1.028-1.058; p<0.01) and the number of comorbidities (OR 1.229; 1.119-1.350; p<0.01) were significantly associated with pDDI.

Conclusion

The very patient population that may benefit most from treatment with nirmatrelvir/ritonavir also has the greatest risk of pDDI. Polypharmacy is frequently present in these patients and a conscientious check of the comedication is mandatory before a treatment with nirmatrelvir/ritonavir can be initiated.
Key drivers of innovation trajectories and catch-up in latecomer firms: absorptive capacity and opportunity capture
Authors: Petti Claudio , Hu Xinyue , Tang Yongli , Schiuma Giovanni
Published: February 2025

This paper investigates why some latecomer firms with substantial absorptive capacity fail during catch-up phases. It aims to clarify the performance effects of their incremental versus radical innovation trajectories propelled by potential and realized absorptive capacities and the interplay with opportunity capture. The empirical investigation was conducted with a sample of 166 manufacturing firms in Guangdong Province, China. The results indicate that both potential and realized absorptive capacities and opportunity capture are more effective in enhancing the performance of incremental innovations than those of radical innovations. However, a high level of opportunity capture can diminish the beneficial impacts of absorptive capacity on radical innovation performance to a greater extent. These findings enrich extant literature on latecomer firms’ catch-up strategies by combining the theoretical lens of absorptive capacity and opportunity capture. It offers implications for managers and policymakers, guiding strategy and policy formulation for firm catch-up endeavors.
Surgical techniques in chondrolaryngoplasty: a narrative review
Authors: de Almeida Rodolfo B S , Costa Claudiney C , Ramos Hugo V L , e Silva Duarte Pauliana L , Velasco Leandro C , Cervantes Onivaldo
Published: February 2025

Introduction

Chondrolaryngoplasty, also known as “Adam’s apple” reduction, is a surgical procedure that diminishes the prominence of the thyroid cartilage. Primarily sought by transgender women, the procedure is performed for esthetic reasons to align with their identified gender. It can also be done for cisgender individuals seeking reduced prominence. Despite its safety, there are risks due to the proximity to vocal cords, and variations may impact results.

Objective

To identify the main techniques available in the literature for performing chondrolaryngoplasty, as well as the differences in the results of each technique applied.

Methods

Research utilized databases (MEDLINE, PubMed, and Scopus) from inception to March 2023, focusing on randomized clinical trials, prospective and retrospective studies, and case series published in English, Spanish, French, or Portuguese. Selected studies provided results including satisfaction rates, surgical time, and/or details on complications.

Results

21 eligible results, four of which were excluded because the full text was not available and four because they did not meet the research objectives. Thus, 13 articles were included in the analysis, eight of which reported on external approach surgical procedures (via surgical incision) and five on transoral procedures, totaling 355 living patients evaluated, as well as 11 cadavers. The complications reported are considered mild and transient, and do not contraindicate the procedure. Among the factors that most interfere with patient satisfaction is the apparent scar, which is avoided with the transoral surgical approach, which has been reported more recently.

Conclusion

Chondrolaryngoplasty is an esthetic surgical procedure that aims to reduce the prominence of the thyroid cartilage and is most commonly performed on transgender women. Studies show that it is a safe procedure, with rare complications that are generally transient. The main drawback of the surgery is the apparent scar which can be avoided by a transoral approach.
Global Patterns of Taxonomic Uncertainty and its Impacts on Biodiversity Research
Authors: Guedes Jhonny J M , Moura Mario R , Jardim Lucas , Diniz-Filho José Alexandre F
Published: February 2025

Over two million species have been named so far, but many will be invalidated due to redundant descriptions. Undetected invalid species (i.e., synonyms) can impair inferences we make in biodiversity research and hamper the implementation of effective conservation strategies. However, the processes leading to the accumulation of invalid names remain largely unknown. Using multi-model inferences, we investigated the patterns and potential drivers of species- and assemblage-level variation in synonym counts across terrestrial vertebrates globally. We also explored how taxonomic uncertainty (i.e., instability in species identities) can affect latitudinal variation of diversification rates. The average number of synonyms was higher for species described earlier, better represented in scientific collections, with larger geographic ranges, occurring in temperate regions, and in areas of high biodiversity attention. In assemblage-level models, a higher average number of synonyms was associated with temperate regions harbouring more early-described species. Areas of high endemism richness showed fewer synonyms across amphibians and reptiles but had an inverse effect for birds and mammals. Other predictor-response relationships varied across taxonomic groups, biogeographical realm, and spatial grain. Assuming that more synonyms indicate more stable species that have been thoroughly studied and reviewed, high synonym numbers in temperate species and assemblages support claims of a potential latitudinal taxonomy gradient, where geographic variation in taxonomic practice could hinder the proper recognition of tropical species. We show that the accumulation of invalid names is not random and discuss how invalid hidden names can affect biodiversity inferences. A potential approach to address this problem would be developing a taxonomic uncertainty metric that could be incorporated into models (i.e., as weights to account for varying degrees of uncertainty during the fitting process). Our study provides an initial approximation and highlights the often-neglected issue of uncertainty and instability in species identities from a macroecological perspective.
Molecular phylogeny of Salmoneus Holthuis, 1955 and its satellite genera (Decapoda: Caridea: Alpheidae) reveals hidden diversity and multiple instances of morphological and ecological convergence
Authors: Ashrafi Hossein , Anker Arthur , Ďuriš Zdeněk
Published: February 2025

The present study deals with the intricate phylogenetic relationships within an important clade of the caridean shrimp family Alpheidae, which includes the genera Salmoneus, Deioneus, and Triacanthoneus. Using molecular data from four genes (16S, 18S, COI, and H3), we herein provide the most comprehensive phylogenetic hypothesis for this alpheid clade, with 161 terminals representing 117 ESUs, i.e. genetically distinct species. Our analysis reveals four well-supported larger Clades, as well as 25 smaller clades, corresponding to species groups or species complexes. The results also show that the symbiotic lifestyle evolved multiple times within this clade, in some instances promoting convergent evolution. Ancestral character state analysis unveils extreme plasticity and independent shifts in the minor cheliped types. Furthermore, the impact of different lifestyles on the evolution of each minor cheliped type is discussed. Finally, we address the resulting paraphyly of Salmoneus and the intergeneric relationships between Salmoneus, Deioneus and Triacanthoneus.
Cell cycle‐based antibody selection for suppressing cancer cell growth
Authors: Song Chi Hun , Lin Chih‐Wei , Han Kyung Ho
Published: February 2025

Cell cycle arrest and programmed cell death are crucial biological processes in cancer development. Regulating cell fate decisions is essential due to their potential to induce cell cycle arrest and cell death. Inducing cell cycle regulatory proteins in tumor cells is considered a key objective in cancer therapy. Here, we present a novel method that selects antibodies from an antibody library to inhibit cancer growth using fluorescence‐activated cell sorting (FACS) assays and cell cycle analysis. This approach seeks antibodies that induce cancer cells to enter the G0 or G1 phase, a quiescent state where cells cease to proliferate and trigger programmed cell death. We found that the T1 antibody effectively suppresses the proliferation of cancer cells. Mechanistically, serine protease 3 (PRSS3) is a target antigen of the T1 antibody. We demonstrated that PRSS3 controls tumor cell proliferation and apoptosis through interaction with the T1 antibody. This research suggests that PRSS3 holds great potential as a target for solid cancer treatment. This cycle‐based approach to antibody screening shows potential because it can be broadly applied to cancer and other challenging diseases.
The Readability, Actionability, and Accessibility of Hemorrhoid-Focused Online Patient Education Materials: Are We Adequately Addressing Patient Concerns?
Authors: Eng Isabel K. , Chen Formosa , Russell Marcia M. , May Folasade P. , Labora Amanda , Salinas Daniela , Russell Tara A.
Published: February 2025

BACKGROUND:

Hemorrhoidal disease is highly prevalent in the United States and frequently queried online. Unfortunately, health education webpages often lack reliable information.

OBJECTIVE:

To evaluate whether online hemorrhoid education materials in English and Spanish meet national recommendations for readability, actionability, and accessibility, and provide critical clinical guidance on when to seek medical care.

DESIGN:

Using three search engines (Bing, Google, Yahoo), we selected the top 30 results for formal medical and colloquial English and Spanish search terms regarding hemorrhoids. We assessed readability using validated scoring systems for readability in English and Spanish to report median reading levels and assessed Health Literacy Performance on a six-point checklist in three categories: accessibility, actionability, and critical clinical guidance.

SETTINGS:

University of California Los Angeles.

MAIN OUTCOME MEASURES:

Readability and health literacy performance.

RESULTS:

After removing duplicates, 90-95 webpages generated from formal English, Spanish, and colloquial English terms remained. There was minimal overlap of results from the formal and colloquial English searches. Median reading levels were first-year university for formal and colloquial English webpages, and eleventh grade for Spanish webpages. 43.2%, 48.4%, and 18.2% of formal English, Spanish, and colloquial English websites, respectively, had minimal Health Literacy Performance. Health Literacy Performance criteria that were met least often were printability and providing specific, actionable goals for patients to implement.

LIMITATIONS:

Our study represents searches completed at one point in time utilizing specific terms. Colloquial search terms were generated via survey with convenience sampling and may not be representative of all possible searches used by patients seeking information on hemorrhoidal disease.

CONCLUSIONS:

Most English and Spanish hemorrhoid-focused webpages failed to provide appropriate patient education, as they exceeded the recommended sixth-grade reading level, lacked actionable recommendations, were not accessible, and failed to provide critical clinical guidance. Online resources are essential for patients of all health literacy levels; improvement is critical to reduce healthcare disparities. See Video Abstract.
Validation and Sensitivity Analysis of the COVID-19 Transmission Model Simulating Counterfactual Infections in Japan
Authors: Kakeya Hideki , Umeno Yoshitaka
Published: February 2025

Background

Kayano et al. estimated the potential number of COVID-19 cases and deaths in Japan from February 17 to November 30, 2021, in a counterfactual scenario where no vaccination was implemented. Their model predicted 63.3 million cases and 364,000 deaths, with a claimed 95% confidence interval of less than 1% of the estimated values.

Objective

To validate the transmission model used by Kayano et al. by simulating infection counts in Japan during 2020 and assessing the impact of errors in the reproduction number of the Delta variant on infection count estimates in the counterfactual scenario.

Methods

We replicated the model used by Kayano et al. to simulate infection dynamics in Japan during 2020. We evaluated the model’s performance by comparing the simulated infection surges with actual data. Additionally, we analyzed the sensitivity of infection count estimates to ±10% errors in the reproduction number of the Delta variant, corresponding to the 95% confidence interval reported in the cited study.

Results

The model successfully reproduced the first infection surge in early 2020, but it failed to replicate the second and third infection surges in the summer and winter of 2020. Sensitivity analysis revealed that a ±10% error in the reproduction number led to an estimated infection count error range of −25% to +42%.

Conclusion

The results suggest potential limitations in the validity of the counterfactual simulation results presented by Kayano et al., particularly regarding the accuracy of infection count estimates and the confidence interval.
Large-scale genomic surveillance reveals immunosuppression drives mutation dynamics in persistent SARS-CoV-2 infections
Authors: Khurana Mark P. , Katsiferis Alexandros , Scheidwasser Neil , Sloth Mathilde Marie Brunnich , Curran-Sebastian Jacob , Morgenstern Christian , Tang Man-Hung Eric , Fonager Jannik , Rasmussen Morten , Stegger Marc , Whittaker Charles ,   The Danish COVID-19 Genome Consortium (DCGC), Lehmann Sune , Mortensen Laust H. , Jokelainen Pikka , Kraemer Moritz U.G. , Ferguson Neil M. , Ghafari Mahan , Krause Tyra G. , Duchene David A. , Bhatt Samir
Published: February 2025

Persistent SARS-CoV-2 infections have been hypothesized to play a key role in the emergence of variants of concern. However, the factors determining which individuals are at risk and their viral molecular signatures during infection remain poorly understood. Using the extensive COVID-19 surveillance database in Denmark, comprising over 700,000 genomes, we identified 303 persistent infections and, critically, linked them to health and sociodemographic data. Our analysis confirms the hypothesis that immunocompromised individuals are at the highest risk of experiencing persistent infections. Other disease groups associated with mortality, such as diabetes, showed no such associations. Among these persistent infections, the viral sequences exhibited signs of diversifying selection, with recurrent mutations linked to treatment resistance. Our findings suggest that immunosuppression plays a key role in the emergence of novelty in persistent infections.
Chemical coupling of biological magnetosomes with amine-functionalized therapeutic antibody conjugates
Authors: Payan S.M , Gandarias L , Avellan R , Faivre D , Prévéral S
Published: February 2025

Background

Immunotherapy, particularly in cancer treatment, can be enhanced using antibody-drug or antibody-radionuclide conjugates. These conjugates disrupt cell signaling and induce cell death, requiring the targeted antigen to be highly expressed on tumor cells to avoid damage to healthy tissues. A promising strategy to improve delivery is the use of magnetosomes, biological magnetic nanoparticles, which can be guided to tumor sites using magnetic fields. However, most antibody-drug or antibody-radionuclide conjugates are functionalized using the antibody amine groups of the lysine residues on the heavy chains. Therefore, these amine groups are no longer available to bind the antibodies to the magnetosomes.

Results

Here, we explore an alternative approach to bind amine-functionalized antibodies to magnetosomes. Using SulfoSuccinimidyl-4-(N-Maleimidomethyl)Cyclohexane-1-Carboxylate (S-SMCC) as a crosslinker, the antibodies are chemically attached to the magnetosome membrane via thiol groups through antibody partial reduction. Our results demonstrate that this chemical process preserves the integrity and functionality of both magnetosomes and antibodies. Moreover, we prove that the produced magnetosome-antibody conjugates are stable under variousin vivo-like conditions.

Conclusion

This coupling method offers significant advantages, enabling the coupling of therapeutic molecules to antibodies combined with the magnetic properties of magnetosomes. This new strategy aims to improve cancer therapy through targeted delivery and rapid accumulation at tumor sites.
Deep learning-based prediction of tissue-specific splice sites in the human neural retina
Authors: Riepe Tabea V. , de Bruijn Suzanne E. , Roosing Susanne , Cremers Frans P.M. , Hoen Peter A.C. ‘t
Published: February 2025

Splice prediction tools can be used to identify splice-altering variants in patients with inherited diseases. Since splicing is tissue-specific, a predicted splice defect may vary depending on the tissue of interest. Current splice prediction tools often neglect splice junctions from the human neural retina, which can lead to the misinterpretation of benign and pathogenic variants in patients with inherited retinal diseases (IRDs). To address this issue, we developed a retina-specific splice prediction tool based on the model architecture of SpliceAI. In addition to retraining the existing model using splice junctions derived from retina RNA-sequencing data, we also improved the model’s generalization through hyperparameter optimizations such as dropout. The resulting retina-specific model was validated on retina-enriched exons and variants known to cause retina-specific splicing defects. Although the retina model correctly identified five more retina-enriched splice sites than the GTEx model, it did not enhance predictions for variants with tissue-specific splicing defects nor did it identify novel pathogenic variants in a set of genetically unexplained IRD cases. Despite these limitations, the retina-specific SpliceAI model shows promising results and should be applied to a larger patient cohort to uncover novel splice-altering variants in IRD patients.