bluuebunny/crossref_metadata_2025 huggingface dataset:
Somy evolution in the honey bee infecting trypanosomatid parasite Lotmaria passim
Authors: Markowitz Lindsey M , Nearman Anthony , Zhao Zexuan , Boncristiani Dawn , Butenko Anzhelika , de Pablos Luis Miguel , Marin Arturo , Xu Guang , Machado Carlos A , Schwarz Ryan S , Palmer-Young Evan C , Evans Jay D
Published: November 2024

Lotmaria passim is a ubiquitous trypanosomatid parasite of honey bees nestled within the medically important subfamily Leishmaniinae. Although this parasite is associated with honey bee colony losses, the original draft genome—which was completed before its differentiation from the closely related Crithidia mellificae—has remained the reference for this species despite lacking improvements from newer methodologies. Here, we report the updated sequencing, assembly, and annotation of the BRL-type (Bee Research Laboratory) strain (ATCC PRA-422) of Lotmaria passim. The nuclear genome assembly has been resolved into 31 complete chromosomes and is paired with an assembled kinetoplast genome consisting of a maxicircle and 30 minicircle sequences. The assembly spans 33.7 Mb and contains very little repetitive content, from which our annotation of both the nuclear assembly and kinetoplast predicted 10,288 protein-coding genes. Analyses of the assembly revealed evidence of a recent chromosomal duplication event within chromosomes 5 and 6 and provided evidence for a high level of aneuploidy in this species, mirroring the genomic flexibility employed by other trypanosomatids as a means of adaptation to different environments. This high-quality reference can therefore provide insights into adaptations of trypanosomatids to the thermally regulated, acidic, and phytochemically rich honey bee hindgut niche, which offers parallels to the challenges faced by other Leishmaniinae during the challenges they undergo within insect vectors, during infection of mammals, and exposure to antiparasitic drugs throughout their multi-host life cycles. This reference will also facilitate investigations of strain-specific genomic polymorphisms, their role in pathogenicity, and the development of treatments for pollinator infection.
Population size rescaling significantly biases outcomes of forward-in-time population genetic simulations
Authors: Dabi Amjad , Schrider Daniel R
Published: November 2024

Simulations are an essential tool in all areas of population genetic research, used in tasks such as the validation of theoretical analysis and the study of complex evolutionary models. Forward-in-time simulations are especially flexible, allowing for various types of natural selection, complex genetic architectures, and non-Wright–Fisher dynamics. However, their intense computational requirements can be prohibitive to simulating large populations and genomes. A popular method to alleviate this burden is to scale down the population size by some scaling factor while scaling up the mutation rate, selection coefficients, and recombination rate by the same factor. However, this rescaling approach may in some cases bias simulation results. To investigate the manner and degree to which rescaling impacts simulation outcomes, we carried out simulations with different demographic histories and distributions of fitness effects using several values of the rescaling factor, Q, and compared the deviation of key outcomes (fixation times, allele frequencies, linkage disequilibrium, and the fraction of mutations that fix during the simulation) between the scaled and unscaled simulations. Our results indicate that scaling introduces substantial biases to each of these measured outcomes, even at small values of Q. Moreover, the nature of these effects depends on the evolutionary model and scaling factor being examined. While increasing the scaling factor tends to increase the observed biases, this relationship is not always straightforward; thus, it may be difficult to know the impact of scaling on simulation outcomes a priori. However, it appears that for most models, only a small number of replicates was needed to accurately quantify the bias produced by rescaling for a given Q. In summary, while rescaling forward-in-time simulations may be necessary in many cases, researchers should be aware of the rescaling procedure's impact on simulation outcomes and consider investigating its magnitude in smaller scale simulations of the desired model(s) before selecting an appropriate value of Q.
Nonparticipation in a Digital Health Intervention Study Among Older Adults: Uneven Involvement, Biased Outcomes, and the Effect of Weighting
Authors: Poli Arianna , Kåreholt Ingemar , Kelfve Susanne , Berg Katarina , Motel-Klingebiel Andreas
Published: November 2024

Background

The involvement of older adults in research on digital health is uneven with respect to, for example, age, gender, health status, and digital skills. However, little is known regarding the effect of the uneven involvement of older adults in digital health research on researched outcomes. This study helps to fill this knowledge gap, identifies the effects of uneven involvement of older adults in digital health research on researched outcomes, and also develops a correction for this.

Methods

Data are retrieved from a digital health intervention for postoperative monitoring of people who underwent day surgery in Sweden. Based on field information on the recruitment process and researched outcomes for the intervention, this study (i) tested intervention effects by using 2 standard unweighted procedures in a sample of 281 individuals aged 50 years or older, and then (ii) used the information on participants, nonparticipants, and their respective probabilities to be involved in the intervention study to perform a weighting of the intervention effects for each step of selection and for the study group membership.

Results

The intervention effects were found to be overestimated due to overrepresentation of groups that gained from receiving the intervention. No intervention effects were found after adjustment for participation bias.

Conclusions

Selective participation of older adults in digital health research biases research outcomes and can lead to overestimation of intervention effects. Weighting allows researchers to correct and describe the effect of selective participation on researched outcomes.
Metrics of Physiological Network Topology Are Novel Biomarkers to Capture Functional Disability and Health
Authors: Hao Meng , Zhang Hui , Jiang Shuai , Hu Zixin , Jiang Xiaoyan , Wu Jingyi , Li Yi , Jin Li , Wang Xiaofeng
Published: November 2024

Background

Physiological networks are highly complex, integrating connections among multiple organ systems and their dynamic changes underlying human aging. It is unknown whether individual-level network could serve as robust biomarkers for health and aging.

Methods

We used personalized network analysis to construct a single-sample network and examine the associations between network properties and functional disability in the Rugao Longevity and Aging Study (RuLAS), the China Health and Retirement Longitudinal Study (CHARLS), the Chinese Longitudinal Healthy Longevity Survey (CLHLS), and the National Health and Nutrition Examination Survey (NHANES).

Results

We observed impairments in interconnected physiological systems among long-lived adults in RuLAS. Single-sample network analysis was applied to reflect the co-occurrence of these multisystem impairments at the individual level. The activities of daily living (ADL)-disabled individuals’ networks exhibited notably increased connectivity among various biomarkers. Significant associations were found between network topology and functional disability across RuLAS, CHARLS, CLHLS, and NHANES. Additionally, network topology served as a novel biomarker to capture risks of incident ADL disability in CHARLS. Furthermore, these metrics of physiological network topology predicted mortality across 4 cohorts. Sensitivity analysis demonstrated that the prediction performance of network topology remained robust, regardless of the chosen biomarkers and parameters.

Conclusions

These findings showed that metrics of network topology were sensitive and robust biomarkers to capture risks of functional disability and mortality, highlighting the role of single-sample physiological networks as novel biomarkers for health and aging.
Supporting multidrug-resistant or rifampicin-resistant TB treatment adherence in people with harmful use of alcohol through person-centred care
Authors: Harrison Rebecca E , Shyleika Volha , Vishneuski Raman , Leonovich Olga , Vetushko Dmitri , Skrahina Alena , Mar Htay Thet , Garsevanidze Ekaterine , Falkenstein Christian , Sayakci Öznur , Martin Antonio Isidro Carrion , Tan Cecilio , Sitali Norman , Viney Kerri , Lonnroth Knut , Stringer Beverley , Ariti Cono , Sinha Animesh
Published: November 2024

Background

TB is concentrated in populations with complex health and social issues, including alcohol use disorders (AUD). We describe treatment adherence and outcomes in a person-centred, multidisciplinary, psychosocial support and harm reduction intervention for people with multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB) with harmful alcohol use.

Methods

An observational cohort study, including multilevel mixed-effects logistic regression and survival analysis with people living in Minsk admitted with MDR/RR-TB and AUD during January 2019–November 2021 who received this person-centred, multidisciplinary, psychosocial support and harm reduction intervention, was conducted.

Results

There were 89 participants enrolled in the intervention, with a median follow-up of 12.2 (IQR: 8.1–20.5) mo. The majority (n=80; 89.9%) of participants had AUD, 11 (12.4%) also had a dependence on other substances, six (6.7%) a dependence on opioids and three (3.4%) a personality disorder. Fifty-eight had a history of past incarceration (65.2%), homelessness (n=9; 10.1%) or unemployment (n=55; 61.8%). Median adherence was 95.4% (IQR: 90.4–99.6%) and outpatient adherence was 91.2% (IQR: 65.1–97.0%). Lower adherence was associated with hepatitis C, alcohol plus other substance use and outpatient facility-based treatment, rather than video-observed treatment, home-based or inpatient treatment support.

Conclusions

This intervention led to good adherence to MDR/RR-TB treatment in people with harmful use of alcohol, a group usually at risk of poor outcomes. Poor outcomes were associated with hepatitis C, other substance misuse and outpatient facility-based treatment support.
Rapid viral suppression using integrase inhibitors during acute HIV-1 infection
Authors: McKellar Mehri S , Keys Jessica R , Filiatreau Lindsey M , McGee Kara S , Kuruc Joann D , Ferrari Guido , Margolis David M , Eron Joseph J , Hicks Charles B , Gay Cynthia L
Published: November 2024

Background

Antiretroviral therapy (ART) is recommended for all individuals with HIV infection, including those with acute HIV-1 infection (AHI). While recommendations are similar to those for chronic infection, efficacy data regarding treatment of acute HIV is limited.

Methods

This was a single arm, 96-week study of a once-daily integrase inhibitor (INSTI)-based regimen using elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) in AHI. Primary endpoint was proportion of participants with HIV-1 RNA <200 copies/mL and <50 copies/mL by treatment weeks 24 and 48, respectively. We also examined time to viral suppression and weight gain after treatment initiation. Outcomes and characteristics were compared with a historical AHI cohort using a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF).

Results

Thirty-three participants with AHI were enrolled with 31 available for analyses. Most were African American (61%) and men who have sex with men (73%). Median age was 26 (IQR 22–42). Demographics were similar between the two AHI cohorts. By Week 24, 100% in the INSTI and 99% in the NNRTI cohort were <200 copies/mL; by Week 48, 100% in both cohorts were <50 copies/mL. Time to viral suppression was shorter in the INSTI cohort (median 54 versus 99 days). Mean weight change was similar with a 3.6 kg increase in the INSTI cohort and 2.4 kg in the NNRTI cohort at 96 weeks.

Conclusions

INSTI-based ART during AHI resulted in rapid and sustained viral suppression. Over 96 weeks, weight increased in the INSTI-based cohort but was similar to weight increase in a historical NNRTI-based AHI cohort.
Emergence of the mobile RND-type efflux pump gene cluster tmexCD1-toprJ1 in Klebsiella pneumoniae clinical isolates in Japan
Authors: Hirabayashi Aki , Yano Hirokazu , Yahara Koji , Aoki Sadao , Sugawara Yo , Kajihara Toshiki , Shibayama Naomi , Kayama Shizuo , Suzuki Masato , Sugai Motoyuki
Published: November 2024

Background

Tigecycline is an antimicrobial agent with a broad spectrum of activity against both Gram-positive and Gram-negative bacteria. However, mobile tigecycline resistance gene clusters, such as tnfxB-tmexCD-toprJ, have spread globally. The prevalence of tigecycline-resistant Enterobacterales in clinical settings in Japan is unknown.

Objectives

To investigate the tnfxB-tmexCD-toprJ gene cluster in the genome sequences of Enterobacterales clinical isolates in Japan.

Methods

We investigated the tnfxB-tmexCD-toprJ cluster from the genome sequences of 5143 Enterobacterales isolates collected from 175 hospitals around Japan between 2019 and 2020 as part of a national genomic surveillance program for antimicrobial-resistant bacteria.

Results

The tnfxB1-tmexCD1-toprJ1 cluster was detected in two Klebsiella pneumoniae isolates in 2019. One isolate possessed a 299.4 kb IncFIB(K) plasmid, pJBBGAAF19431, and the other possessed a 224.9 kb IncHI1B/IncFIB(K) hybrid plasmid, pJBEAACG19501, co-carrying multiple antimicrobial resistance genes, including extended-spectrum β-lactamase genes, blaOXA-1 and blaCTX-M-27, respectively, along with tnfxB1-tmexCD1-toprJ1. The genetic context of the tnfxB1-tmexCD1-toprJ1-surrounding structure on pJBBGAAF19431 was similar to that of a K. pneumoniae plasmid pHNAH8I-1 from a chicken in China in 2017, and the cluster was embedded in an apparently intact mobile DNA element: strand-biased circularizing integrative element. The tnfxB1-tmexCD1-toprJ1 on pJBEAACG19501 was embedded in a Tn3 family transposon related to TnAs1. The plasmid pJBEAACG19501 was highly similar to that of K. pneumoniae, isolated from humans in China in 2021.

Conclusions

tmexCD-toprJ was present in Japan as of 2019. Even in Japan, where the clinical use of tigecycline is significantly rare, tmexCD-toprJ-harbouring multidrug-resistant Enterobacterales is a public health threat and requires continuous monitoring.
Toward the bioleaching of bauxite residue by Gluconobacter oxydans
Authors: van Wyk Nathan , Fischer Dorte , Wilbers Derik , Harrison Susan T L , Kotsiopoulos Athanasios , Dopson Mark
Published: November 2024

Aim

This project evaluated a biologically mediated strategy to solubilize several rare earth elements and critical raw materials, including scandium, from bauxite residue. This work seeks to expand on previous research on contact leaching with bauxite.

Methods and results

In this study, Gluconobacter oxydans was shown to secrete mixed organic acids, including gluconic acid, which was superior to pure gluconic acid in the dissolution of bauxite residue, even at low molarities. In situ contact leaching with G. oxydans significantly promoted the dissolution yield (recovery of metal present in the ore) of yttrium, aluminum, calcium, and titanium (41.18%, 67.79%, 80.16%, and 59.41%, respectively) but allowed for only marginal dissolution yield of scandium, lanthanum, cerium, and neodymium (13.40%, 14.74%, 24.41%, and 10.67%, respectively) at relatively low pulp densities. In addition, the dissolution yields of rare earth elements were reduced further with time, presumably as the oxides of these elements fell out of solution.

Conclusion

This work builds on previous research that seeks to extract rare earth elements and critical raw materials from bauxite residue through contact leaching with organic acids. Some elements such as yttrium, aluminum, calcium, and titanium could be effectively solubilized; however some elements showed reduced solubility, possibly due to tight association with the iron phase of the residue. However, the relative ease and speed of leaching, and improved solubilization, suggest that this could be a viable method for securing critical raw material supplies.
Bcl2l12, a novel protein interacting with Arf6, triggers Schwann cell differentiation programme
Authors: Miyata Wakana , Sakaibara Naoko , Yoshinaga Kentaro , Honjo Asahi , Takahashi Mikito , Ooki Tatsuya , Yako Hideji , Sango Kazunori , Miyamoto Yuki , Yamauchi Junji
Published: November 2024

Schwann cells are glial cells in the peripheral nervous system (PNS); they wrap neuronal axons with their differentiated plasma membranes called myelin sheaths. Although the physiological functions, such as generating saltatory conduction, have been well studied in the PNS, the molecular mechanisms by which Schwann cells undergo their differentiation programme without apparent morphological changes before dynamic myelin sheath formation remain unclear. Here, for the first time, we report that Arf6, a small GTP/GDP-binding protein controlling morphological differentiation, and the guanine–nucleotide exchange factors cytohesin proteins are involved in the regulation of Schwann cell differentiation marker expression in primary Schwann cells. Specific inhibition of Arf6 and cytohesins by NAV-2729 and SecinH3, respectively, decreased expression of marker proteins 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) and glial fibrillary acidic protein (GFAP). Similar results using promoter assays were observed using the IMS32 Schwann cell line. Furthermore, using an affinity-precipitation technique, we identified Bcl2-like 12 (Bcl2l12) as a novel GTP-bound Arf6-interacting protein. Knockdown of Bcl2l12 using a specific artificial miRNA decreased expression of marker proteins. The knockdown also led to decreased filamentous actin extents. These results suggest that Arf6 and Bcl2l12 can trigger Schwann cell differentiation, providing evidence for a molecular relay that underlies how Schwann cells differentiate.
Consumers Prefer Products That Work Using Directionally Consistent Causal Chains
Authors: Bharti Soaham , Sussman Abigail B
Published: November 2024

Products often aim to help consumers achieve desired outcomes such as increasing energy levels or removing fabric stains. These products typically work via rich causal paths. The current research suggests that the structure of these paths influences consumer judgments of product efficacy. In particular, sequential steps in these paths can evoke distinct directionalities—either increasing or decreasing variables in each step along the way. For example, a face cream could be described as “increasing the turnover of skin cells to reduce wrinkles.” Under our framework, the action influencing skin cells would correspond to increasing directionality, while the action influencing wrinkles would correspond to decreasing directionality. Ten experiments provide evidence that consumers prefer products with directionally consistent causal chains (ie, all steps evoking the same directionality) over those with directionally inconsistent ones (ie, steps evoking contrasting directionalities). This occurs because consumers find directionally consistent causal chains easier to process which in turn leads them to infer higher efficacy from products working via such consistent chains. These findings advance our understanding of how consumers evaluate product descriptions and provide prescriptions for marketers tasked with composing product descriptions to convey efficacy.
Foraging behavior and work patterns of Bombus terrestris (Hymenoptera: Apidae) in response to tomato greenhouse microclimate
Authors: Wang Huan , Qu Yanyan , He Xujiang , Xu Xi-lian , Wang Rufang , Xue Meijing , Zeng Zhi-jiang
Published: November 2024

Bumblebees play a significant role as pollinators for many wild plants and cultivated crops, owing to their elongated proboscis, resilience to diverse weather conditions, robustly furred bodies, and their unique capacity for buzz-pollination. To better understand the effect of greenhouse microclimates on bumblebee foraging behavior and working modes, a long-term record of foraging activity for each Bombus terrestris L. (Hymenoptera: Apidae) forager was monitored by the Radio-frequency identification system. The pattern of task performance, including constant housing, foraging, and day-off rotation, was examined under the microclimate. In addition, the correlation between foraging activity of bumblebees and temperature, relative humidity, illumination in the greenhouse, and pollen viability of tomato plants was further analyzed. Our findings revealed that B. terrestris can respond to microclimatic factors and plant resources while also exhibiting a suitable working pattern within the colony. Day-off rotation was observed as a strategy employed by foragers to prolong their survival time. This division of labor and task rotation may serve as strategies for the survival and development of the colony. Our research may contribute to fully understanding how microclimate and plants influence pollinator behavior within greenhouses, thereby optimizing the pollination management of bumblebees on greenhouse crops.
Combining sterile insect releases with refuge areas to delay the evolution of resistance to Bt sugarcane: an agent-based modeling approach
Authors: Potgieter Linke , Human Dirk J , Downing Samantha
Published: November 2024

The strategic use of refuge areas is a well-known method for delaying the development of pest resistance to Bacillus thuringiensis (Bt) crop. A lesser-known method to control against resistance development is sterile insect releases. In this article, an agent-based simulation model is used to test the effectiveness of combining the use of Bt sugarcane, refuge areas, and sterile insect releases as an integrated strategy against Eldana saccharina Walker (Lepidoptera: Pyralidae) infestation and resistance development. Individual insects are modeled with their own genetic traits on a simulated sugarcane field that represents either Bt or refuge area. The model is applied to 2 hypothetical case studies. In the first experiment, resistance development and infestation dynamics in Bt sugarcane without refuge areas are considered using various sterile:wild sterile release ratios, and different release distributions. In the second experiment, the inclusion of a refuge area in Bt sugarcane is considered, using various sterile:wild releases ratios and different release distributions. A trade-off between sterile insect releases and the use of the refuge area was observed, and could, in some cases, work against each other.
Glutamine modulates neutrophil recruitment and effector functions during sterile inflammation
Authors: Hellenthal Katharina E M , Thomas Katharina , Ludwig Nadine , Cappenberg Anika , Schemmelmann Lena , Tekath Tobias , Margraf Andreas , Mersmann Sina , Henke Katharina , Rossaint Jan , Zarbock Alexander , Amini Wida
Published: November 2024

During sterile inflammation, tissue damage induces excessive activation and infiltration of neutrophils into tissues, where they critically contribute to organ dysfunction. Tight regulation of neutrophil migration and their effector functions is crucial to prevent overshooting immune responses. Neutrophils utilize more glutamine, the most abundant free α-amino acid in the human blood, than other leukocytes. However, under inflammatory conditions, the body's requirements exceed its ability to produce sufficient amounts of glutamine. This study investigates the impact of glutamine on neutrophil recruitment and their key effector functions. Glutamine treatment effectively reduced neutrophil activation by modulating β2-integrin activity and chemotaxis in vitro. In a murine in vivo model of sterile inflammation induced by renal ischemia-reperfusion injury, glutamine administration significantly attenuated neutrophil recruitment into injured kidneys. Transcriptomic analysis revealed, glutamine induces transcriptomic reprograming in murine neutrophils, thus improving mitochondrial functionality and glutathione metabolism. Further, glutamine influenced key neutrophil effector functions, leading to decreased production of reactive oxygen species and formation of neutrophil extracellular traps. Mechanistically, we used a transglutaminase 2 inhibitor to identify transglutaminase 2 as a downstream mediator of glutamine effects on neutrophils. In conclusion, our findings suggest that glutamine diminishes activation and recruitment of neutrophils and thus identify glutamine as a potent means to curb overshooting neutrophil responses during sterile inflammation.
The Influence of Skin Microbial Ecology on γδ T Cell Immune Pathways in Allergic Dermatitis Models in Mice
Authors: You Zonghao , Zhang Xiaoyan , Huang Sujie , Chen Denghui , Zhu Yifan , Li Gen , Chen Xi
Published: November 2024

Atopic dermatitis (AD) is a complex disease influenced by alterations in the skin microbiome and immune dysregulation. Despite the recognized role of these factors, the specific pathways by which distinct microbial populations affect skin immunity remain insufficiently understood. On a molecular level, the pathogenesis of AD involves critical cytokines such as IL-4, IL-17, interferon-γ (IFN-γ), and IL-10, which contribute to the imbalance in T helper (Th) cell responses. Importantly, gamma-delta (γδ) T cells, which produce these cytokines and infiltrate affected epithelial cells in AD, have been underexplored. This study seeks to alleviate AD symptoms in mice by adjusting both peripheral and local immune environments through the transplantation of skin microbiota. By employing 16S rRNA sequencing, we characterized the skin microbiome of the mouse model. Our results demonstrate that microbiota intervention significantly reduces skin thickening and serum IgE levels in DNFB-induced AD mice. Additionally, changes in skin microbiota modulated immune cell dynamics, restoring the Th1/Th2 balance and leading to clinical improvement. These findings highlight the critical role of skin microbiota in shaping immune responses, positioning microbiota-based therapies as a potential treatment for AD.
Fusarium spp. causing invasive disease in humans: A case series from north India
Authors: Gourav Sudesh , Mishra Himanshu , Xess Immaculata , Bhalla Ashu Seith , Chandola Stuti , Gupta Sonakshi , Appasami Kavi Priya , Shukla Balaji Dattatraya , Bakhshi Sameer , Manhas Aish , Pandey Mragnayani , Rana Bhaskar , Singh Gagandeep
Published: November 2024

Owing to their inherent resistance to different classes of antifungals, early identification of Fusarium spp. is crucial. In this study, 10 clinical isolates were included from patients with invasive fusariosis involving lungs, sinuses, or both. Clinico-radiological data were collected. Samples were processed by standard laboratory procedures. Three gene regions (ITS, TEF1, and RPB2) were amplified by PCR for multilocus sequencing. Fusarium MLST, FUSARIUM-ID, and FUSARIOID-ID databases were used for final identification. Antifungal susceptibility testing was performed by broth microdilution following CLSI M38-A3 and Sensititre™ YeastOne™ YO9 plate. Pulmonary involvement was seen in all patients, and sino-nasal involvement was present in six. Radiologically, consolidations and cavitations were present in eight and six cases, respectively. Halo sign was present in six; reverse halo sign was also found in three of them. Direct microscopy showed septate hyphae that were morphologically different from those found in aspergillosis. Results of the molecular identification were as follows: two Fusarium irregulare, one Fusarium pernambucanum, one Fusarium incarnatum, one Fusarium sp. FIESC 30, two Fusarium keratoplasticum, one Fusarium falciforme, one Fusarium pseudonygamai, and one Fusarium delphinoides. For both Fusarium solani (FSSC) and Fusarium incarnatum-equiseti (FIESC) species complexes, amphotericin B had the lowest minimum inhibitory concentrations (MICs). Importantly, for terbinafine, all FIESC isolates had low MICs, while FSSC isolates had high MICs. In some cases, early identification of Fusarium spp. is possible by means of morphology of hyphae on direct microscopy and findings on radiology. Molecular identification, at least to the species complex level, is crucial for the choice of antifungals.
Sensitivity analysis of simulation-based inference for galaxy clustering
Authors: Modi Chirag , Pandey Shivam , Ho Matthew , Hahn ChangHoon , Régaldo-Saint Blancard Bruno , Wandelt Benjamin
Published: November 2024

Simulation-based inference (SBI) is a promising approach to leverage high-fidelity cosmological simulations and extract information from the non-Gaussian, non-linear scales that cannot be modelled analytically. However, scaling SBI to the next generation of cosmological surveys faces the computational challenge of requiring a large number of accurate simulations over a wide range of cosmologies, while simultaneously encompassing large cosmological volumes at high resolution. This challenge can potentially be mitigated by balancing the accuracy and computational cost for different components of the forward model while ensuring robust inference. To guide our steps in this, we perform a sensitivity analysis of SBI for galaxy clustering on various components of the cosmological simulations: gravity model, halo finder, and the galaxy–halo distribution models (halo-occupation distribution, HOD). We infer the $\sigma _8$ and $\Omega _\mathrm{ m}$ using galaxy power spectrum multipoles and the bispectrum monopole assuming a galaxy number density expected from the luminous red galaxies observed using the Dark Energy Spectroscopy Instrument. We find that SBI is insensitive to changing gravity model between N-body simulations and particle mesh simulations. However, changing the halo finder from friends of friends to Rockstar can lead to biased estimate of $\sigma _8$ based on the bispectrum. For galaxy models, training SBI on more complex HOD leads to consistent inference for less complex HOD models, but SBI trained on simpler HOD models fails when applied to analyse data from a more complex HOD model. Based on our results, we discuss the outlook on cosmological simulations with a focus on applying SBI approaches to future galaxy surveys.
Find the haystacks, then look for needles: the rate of strongly lensed supernovae in galaxy–galaxy strong gravitational lenses
Authors: Sainz de Murieta Ana , Collett Thomas E , Magee Mark R , Pierel Justin D R , Enzi Wolfgang J R , Lokken Martine , Gagliano Alex , Ryczanowski Dan
Published: November 2024

The time-delay between appearances of multiple images of a gravitationally lensed supernova (glSN) is sensitive to the Hubble constant, $H_0$. As well as time-delays, a lensed host galaxy is needed to enable precise inference of $H_0$. In this work, we investigate the connection between discoverable lensed transients and their host galaxies. We find that the Legacy Survey of Space and Time (LSST) will discover at least 90 glSNe per year, of which 54 per cent will also have a strongly lensed host. The rates are uncertain by approximately 30 per cent depending primarily on the choice of the unlensed SN population and uncertainties in the redshift evolution of the deflector population, but the fraction of glSNe with a lensed host is consistently around a half. LSST will discover around 20 glSNe per year in systems that could plausibly have been identified by Euclid as galaxy–galaxy lenses before the discovery of the glSN. Such systems have preferentially longer time-delays and therefore are well suited for cosmography. We define a golden sample of glSNe Ia with time-delays over 10 d, image separations greater than 0.8 arcsec, and a multiply imaged host. For this golden sample, we find 91 per cent occur in systems that should already be discoverable as galaxy–galaxy lenses in Euclid. For cosmology with glSNe, monitoring Euclid lenses is a plausible alternative to searching the entire LSST alert stream.
Unravelling the Brachidontes variabilis species complex (Bivalvia: Mytilidae) of the Indo-Pacific region
Authors: Tan Samuel Hui Ming , Wells Fred E , Lukehurst Sherralee S , Strong Ellen E , Sanpanich Kitithorn , Duangdee Teerapong , Ambarwati Reni , Tan Koh Siang
Published: November 2024

Members of the radially ribbed mytilid genus Brachidontes are often dominant filter feeders on hard intertidal substrata in the Indo-Pacific region. However, there is still a great deal of uncertainty and confusion over their species identities, taxonomy and phylogenetic relationships. At least six species names (crebristriatus, karachiensis, mutabilis, pharaonis, ustulatus and variabilis) have at one time or another been synonymized with each other and applied to these common intertidal mussels. They occur widely across the Indian and Pacific Oceans from East Africa to Hawaii. Our results, based on sequences of five genes and anatomical features, suggest there are at least eight closely related sibling species in three monophyletic clades: (1) Brachidontes variabilis-form A in the western Indian Ocean; (2) Brachidontes pharaonis in the Red Sea; (3) Brachidontes variabilis-form B, found from India to East Asia; (4) Brachidontes mutabilis, restricted to southern Japan and China; (5) Brachidontes crebristriatus, in the Indian Ocean through to Southeast Asia and Hawaii; (6) Brachidontes ustulatus, an endemic species in western and southern Australia; (7) Brachidontes maritimus, so far known only from Hawaii; and (8) Brachidontes erosus, a southern Australian endemic. The latter two species form a small clade (Clade 1) that is sister to two larger Clades 2 and 3, each comprising three species. Clade 2 contains Brachidontes crebristriatus, Brachidontes mutabilis and Brachidontes ustulatus, whilst Clade 3 is made up of Brachidontes pharaonis, Brachidontes variabilis-form A and variabilis-form B. The shells of these eight species are not only variable but can greatly overlap in morphology. Many are also nearly impossible to distinguish without geographical information. However, the absence or presence of plicate organs in the mantle cavity, and the shape of guard papillae lining the inhalant aperture, may serve as important diagnostic morphological characters when used alongside geographical provenance.
Consensus recommendations for an integrated diagnostic approach to peripheral nerve sheath tumors arising in the setting of Neurofibromatosis Type 1
Authors: Lucas Calixto-Hope G , Gross Andrea M , Romo Carlos G , Dehner Carina A , Lazar Alexander J , Miettinen Markku , Pekmezci Melike , Quezado Martha , Rodriguez Fausto J , Stemmer-Rachamimov Anat , Viskochil David , Perry Arie ,   the Symposium on Atypical Neurofibroma: State of the Science Members, Ahlawat Shivani , Akshintala Srivandana , Amrami Kimberly , Bakker Annette , Belzberg Allan , Blakeley Jaishri O , Bredella Miriam , Chittiboina Prashant , Clapp D Wade , Daldrup-Link Heike , De Raedt Thomas , Dehner Carina , Dombi Eva , Draper Garrett , Fayad Laura , Ferner Rosalie , Fisher Michael J , Gutmann David H , Gross Andrea M , Hawk Kristina , Hirbe Angela , Johnston Fabian , Kim Aerang , Korf Bruce R , Largaespada David , Lazar Alexander , Le Lu , Legius Eric , Levin Adam S , Lucas Calixto-Hope G , Ly Ina , Miettinen Markku , Miller David , Morris Carol , Murphey Mark , Parada Luis , Pekmezci Melike , Perry Arie , Pratilas Christine , Quezado Martha , Ratley Marcus , Ratner Nancy , Rhodes Steven D , Ristow Inka , Rodriguez Fausto , Romo Carlos G , Arenas Eduard Serra , Sheard Steven , Shern John , Siegel Benjamin , Stemmer-Rachamimov Anat , Sundby R Taylor , Szymanski Jeffrey , Vasudevan Harish N , Viskochil David , Weiss Brian D , Well Lennart , Widemann. Brigitte C
Published: November 2024

Consensus recommendations published in 2017 histologically defining atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP) and malignant peripheral nerve sheath tumor (MPNST) were codified in the 2021 WHO Classification of Tumors of the Central Nervous System and the 2022 WHO Classification of Tumors of Soft Tissue and Bone. However, given the shift in diagnostic pathology toward the use of integrated histopathologic and genomic approaches, the incorporation of additional molecular strata in the classification of Neurofibromatosis Type 1 (NF1)-associated peripheral nerve sheath tumors should be formalized to aid in accurate diagnosis and early identification of malignant transformation and enable appropriate intervention for affected patients. To this end, we assembled a multi-institutional expert pathology working group as part of a “Symposium on Atypical Neurofibroma: State of the Science.” Herein, we provide a suggested framework for adequate interventional radiology and surgical sampling and recommend molecular profiling for clinically or radiologically worrisome noncutaneous lesions in patients with NF1 to identify diagnostically-relevant molecular features, including CDKN2A/B inactivation for ANNUBP, as well as SUZ12, EED, or TP53 inactivating mutations, or significant aneuploidy for MPNST. We also propose renaming “low-grade MPNST” to “ANNUBP with increased proliferation” to avoid the use of the “malignant” term in this group of tumors with persistent unknown biologic potential. This refined integrated diagnostic approach for NF1-associated peripheral nerve sheath tumors should continue to evolve in concert with our understanding of these neoplasms.
Association Between Maternal Prepregnancy and Pregnancy Body Mass Index and Children's Telomere Length: A Systematic Review and Meta-analysis
Authors: Lame-Jouybari Amir Hossein , Fahami Mohammad Salar , Hosseini Mahla Sadat , Moradpour Maryam , Hojati Ali , Abbasalizad-Farhangi Mahdieh
Published: November 2024

Context

Telomeres maintain chromosome stability and mark cellular aging, and their shortening with age compromises genomic stability.

Objective

The purpose of this study was to conduct a meta-analysis of existing evidence to evaluate the relationship between the maternal pregnancy body mass index (BMI) and children's telomere length (TL).

Data Source

Web of Science, Scopus, and PubMed databases were systematically searched from their inception to August 27, 2023, for pertinent observational studies.

Data Extraction

The random-effects meta-analysis was conducted on eligible studies that investigated the linear relationship between exposure and the outcomes of interest, utilizing the reported β-coefficient. Cochran’s Q test and I2 statistics were used to assess heterogeneity.

Data Analysis

A significant association was observed between maternal pregnancy BMI and children's TL (32 studies, pooled effect size [ES]: −0.04; 95% CI: −0.06 to −0.01; I2 = 47.51%, P < .001) and maternal prepregnancy BMI and children's TL at birth (16 studies; pooled ES: −0.05; 95% CI: −0.08 to −0.02; I2 = 53.49%, P < .001).

Conclusion

The findings indicate an inverse association between maternal prepregnancy BMI and TL in infants, which is evident within the normal to obese BMI range. This underscores the significance of maternal weight status before pregnancy as a determinant of offspring TL.

Systematic Review Registration

PROSPERO registration no. CRD42023466425.
Targeting RAF1 gene fusions with MEK inhibition in metastatic melanoma
Authors: Khaddour Karam , Haq Rizwan , Buchbinder Elizabeth I , Liu David , Manos Michael P , Ott Patrick A , Hodi F Stephen , Insco Megan L
Published: November 2024

The biological and clinical relevance of gene fusions in melanoma is unknown. Reports and preclinical data have suggested that tumor cells with specific rearrangements such as RAF1 gene fusions could be therapeutically targeted. To investigate the relevance of targeted therapy in patients with melanoma harboring RAF1 gene fusions, we reviewed records of 1268 melanoma patients with targeted sequencing data at the Dana-Farber Cancer Institute. We identified 9 cases and report here on their clinicopathologic characteristics. We describe the favorable outcome of 2 patients who received MEK inhibitor therapy, including 1 patient with a durable response. We coalesced our data with published reports of patients with RAF1 gene fusions who were treated with targeted therapy. We find that single-agent MEK inhibition has anti-tumor activity in melanoma patients harboring an RAF1 gene fusion, and we propose that patients with RAF1 gene fusions should be considered for single-agent MEK inhibitor therapy.
Consequentialism and deontological prohibitions
Authors: Zendejas Medina Pablo
Published: November 2024

It is widely held that deontological moral theories are agent-relative because they include prohibitions on actions such as killing, or breaking promises, which cannot be understood as giving the same goal to different agents. They are thus thought to be inconsistent with consequentialism, in its traditional, agent-neutral form. However, the standard argument for this claim is incomplete, a problem which has led some to make the surprising claim that consequentialism and deontology can be reconciled. I defend the orthodox view, by developing a novel way of establishing agent-relativity, which involves showing that a moral theory admits of interpersonal dilemmas: possible situations where, whatever everyone does, someone must have acted wrongly.
The Cross-Section of Stock Returns Around the World in the Early Twentieth Century
Authors: Braggion Fabio , Driessen Joost , Moore Lyndon
Published: November 2024

We study nine equity markets between 1900 and 1925 to provide an out-of-sample test of some major asset pricing anomalies during a period in which anomalies had not been documented. We find strong evidence of momentum in almost every market. We find no evidence of long-term reversals, which, coupled with the limited presence of institutional investors, suggests that underreaction should be considered as a key aspect of behavioral theories of momentum. We also find evidence for the size effect, betting-against-beta, and the outperformance of low volatility stocks, whereas we find mixed evidence of short-term reversal. (JEL G12, G15, N20)
MUC5B promoter variant and survival in rheumatoid arthritis-associated interstitial lung disease
Authors: Klein Jacob , Wheeler Austin M , Baker Joshua F , Yang Yangyuna , Roul Punyasha , Frideres Halie , Wysham Katherine D , Kerr Gail S , Reimold Andreas , Ascherman Dana P , Kunkel Gary A , Cannon Grant W , Monach Paul A , Poole Jill A , Thiele Geoffrey M , Mikuls Ted R , England Bryant R
Published: November 2024

Objective

The objective of this study was to investigate the association between the MUC5B rs35705950 promoter variant and survival in RA-associated interstitial lung disease (RA-ILD).

Methods

We studied participants in the Veteran Affairs Rheumatoid Arthritis (VARA) registry with validated ILD diagnoses. Participants were followed until death or till the end of the study period. The MUC5B rs35705950 promoter variant was measured using an Infinium genotyping array, assuming autosomal dominant inheritance. Survival and cause of death were determined from VA death records and the National Death Index. Associations of the MUC5B promoter variant with survival were tested in Cox regression models, adjusting for potential confounders.

Results

Among 263 participants with RA-ILD (mean age 69 years, 95% male, 73% White, 85% smoking history), the MUC5B promoter variant was present in 33.5%. The mortality rate was similar between those with [12.2/100 PY (95% CI: 9.4, 15.8)] and without [11.1/100 PY (95% CI: 9.1, 13.5)] the variant. MUC5B status was not significantly associated with survival overall [aHR 0.97 (95% CI: 0.68, 1.37)] or when stratified by ILD pattern [clinical usual interstitial pneumonia (UIP) aHR 0.86 (95% CI: 0.55, 1.35); clinical non-UIP aHR 1.15 (95% CI: 0.63, 2.09)]. Further, MUC5B status was not significantly associated with respiratory-related [aHR 0.83 (95% CI: 0.42, 1.66)] or non-respiratory causes of death [aHR 1.08 (95% CI: 0.72, 1.62)].

Conclusion

While associated with RA-ILD risk, the MUC5B promoter variant was not predictive of survival among RA-ILD patients in this multicentre cohort. Further studies are needed to identify other genetic and non-genetic prognostic factors in RA-ILD to inform disease management.
Serum glutamate dehydrogenase activity enables sensitive and specific diagnosis of hepatocellular injury in humans
Authors: Aubrecht Jiri , Potter David , Sauer John Michael , Warner Roscoe , Johnson Kent J , McGill Mitchell R , Peron Katrina , King Nicholas M P
Published: November 2024

Serum activities of alanine- and aspartate aminotransferases (ALT and AST) are considered the “gold standard” biomarkers of hepatocyte injury in clinical practice and drug development. However, due to the expression of ALT and AST in myocytes, the diagnosis of hepatocellular injury in patients with underlying muscle diseases, including drug-induced muscle injury, is severely limited. Thus, we proposed glutamate dehydrogenase (GLDH) as a liver-specific alternative to serum ALT and AST. In fact, our exploratory studies showed that GLDH has comparable performance to ALT for detecting hepatocyte injury without interference from concomitant muscle injury. Here, we report the results of studies confirming the reference intervals in a healthy human population and the sensitivity and specificity of GLDH for the detection of hepatocyte injury in human subjects. In human subjects, we could not perform liver biopsies due to ethical reasons; we also confirmed the relationship of GLDH and histopathologic lesions using 32 model toxicants in rats. Furthermore, we have shown that injury to tissues that are known to express appreciable levels of GLDH does not affect serum GLDH measurements, indicating excellent liver specificity of serum GLDH. Finally, we observed faster elimination of GLDH than ALT in humans, indicating that decreasing GLDH values could be considered an early sign of recovery. This study provides comprehensive evidence of excellent sensitivity and liver specificity of GLDH for diagnosis of hepatocellular injury, including evaluation of reference intervals, which is essential for the interpretation of serum GLDH in human subjects.