bluuebunny/crossref_metadata_2025 huggingface dataset:
Agricultural practices and pollinators modulate the anthosphere microbiome
Authors: Temmermans Jari , Legein Marie , Checchia Ilaria , Felis Giovanna E , Smets Wenke , Karise Reet , Lebeer Sarah
Published: February 2025

The flower microbiome is pivotal in plant health, influencing reproductive success, fruit quality, and pathogen vulnerability. However, the impact of intensified agricultural practices on these microbial communities remains to be understood. This study examines how specific agricultural practices influence the bacterial composition of the strawberry anthosphere, focusing on cultivation intensification. Intensified systems were defined by practices such as indoor glasshouse substrate-based cultivation, increased use of plant protection products, larger cultivation areas, and reliance on managed pollinators. Using citizen science and V4 16S rRNA gene sequencing, we found that flowers in these more intensively managed systems had lower bacterial diversity, more variable microbiomes, and loss of core taxa such as Sphingomonas and Pseudomonas. To determine if pollinators could help mitigate these effects, we conducted exclusion experiments. In a tunnel system, we observed that foraging pollinators facilitated the dispersal of specific bacteria, such as Staphylococcus and Pseudomonas, and increased flower bacterial richness. However, in an open field, foraging pollinators had no significant impact. Our findings highlight the significant impact of cultivation intensification on the anthosphere microbiome and suggest that pollinators may play a role in restoring microbiome diversity. This research fills a critical gap in understanding how agricultural practices shape plant microbiomes and underscores the potential for microbe-based strategies to improve plant health in intensively managed systems.
The role of CD57+γδ T cells in the immune pathogenesis of patients with sepsis
Authors: Li Liman , Jiang Nenggang , Jin Yongmei , Yang Chuan , Fu Yang
Published: February 2025

The immune response goes haywire during sepsis. The aim of this study was to explore the role of CD57+γδ T cells in the immune pathogenesis of sepsis. We characterized the transcriptomic profile of peripheral γδ T cells obtained from patients with sepsis using the Smart RNA-Sequence. We also analyzed the cell count and the immune functional signatures of CD57+γδ T cells in sepsis using flow cytometry. Besides, the cytotoxicity capacity of CD57+γδ T cell subset and its responses to sepsis-related drug were validated in vitro. Here, we found that patients with sepsis exhibited a reduction in peripheral CD57+γδ T cells proportion, which was positively associated with clinical outcomes. Compared with CD57-γδ T cells, CD57+γδ T cells exhibited drastically altered immunophenotype, including decreased expression levels of costimulatory molecules, higher expression levels of pro-inflammatory factors and cytotoxic granules.
Pediatric Infectious Disease Outpatient Telehealth: An Accepted Model of Care
Authors: Zabalo Celisse , Tsalatsanis Athanasios , Kumar Ambuj , Espinosa Claudia , Purandare Amol , Rodriguez Carina A , Olson Christina , Gaviria-Agudelo Claudia
Published: February 2025

This retrospective cohort study assessed the differences between in person vs telehealth (TH) services in pediatric infectious diseases. TH was noted to be used more frequently by Hispanic patients and established patients. TH decreased travel distance and no-show/cancellation rates. TH offers a valuable outpatient option for pediatric infectious disease patients.
Development of a quantitative SYBR Green real-time PCR and microscopic slide culture for in vitro enumeration of Mycoplasma hyopneumoniae
Authors: Jafari Jozani Raziallah , Al Khallawi Mauida F Hasoon , Mohammed Majed H , Nguyen Hanh Thi Hong , Trott Darren J , Petrovski Kiro , Hemmatzadeh Farhid
Published: February 2025

Mycoplasma hyopneumoniae’s slow growth makes enumeration challenging using the traditional colony-forming unit (CFU) method. We introduced an innovative CFU-slide culture (CFU-SC) approach to address this issue. CFU-SC allows accurate counting of M. hyopneumoniae microcolonies, ranging from 7 to 50 µm, using high magnification. While comparing the accuracy of enumeration among CFU, CFU-SC, quantitative polymerase chain reaction (qPCR), and colour change unit (CCU), we found a robust positive correlation between qPCR and CFU-SC with colourCCU method for quantifying M. hyopneumoniae. Newly isolated strains exhibited the lowest Pearson correlation coefficient (r = 0.52) when comparing CFU and real-time PCR, while the highest coefficient (r = 0.86) was observed for the type strain J and new isolates using real-time PCR and CFU-SC. A consensus growth pattern was observed among all quantification methods, except CFU, between newly isolated strains and the type strain J. Notably, new isolates of M. hyopneumoniae showed no senescence phase after 228 h of cultivation, differing from the type strain J. The disparity in growth rate and pattern between new isolates and the type strain J is evident in the smaller agar microcolonies (7–10 µm) of the isolates, contrasting with the larger colonies (100–200 µm) of type strain J.
Multiomics integration unveils photoperiodic plasticity in the molecular rhythms of marine phytoplankton
Authors: Romero-Losada Ana B , Arvanitidou Christina , García-Gómez M Elena , Morales-Pineda María , Castro-Pérez M José , Chew Yen Peng , van Ooijen Gerben , García-González Mercedes , Romero-Campero Francisco J
Published: February 2025

Earth's tilted rotation and translation around the Sun produce pervasive rhythms on our planet, giving rise to photoperiodic changes in diel cycles. Although marine phytoplankton plays a key role in ecosystems, multiomics analysis of its responses to these periodic environmental signals remains largely unexplored. The marine picoalga Ostreococcus tauri was chosen as a model organism due to its cellular and genomic simplicity. Ostreococcus was subjected to different light regimes to investigate its responses to periodic environmental signals: long summer days, short winter days, constant light, and constant dark conditions. Although <5% of the transcriptome maintained oscillations under both constant conditions, 80% presented diel rhythmicity. A drastic reduction in diel rhythmicity was observed at the proteome level, with 39% of the detected proteins oscillating. Photoperiod-specific rhythms were identified for key physiological processes such as the cell cycle, photosynthesis, carotenoid biosynthesis, starch accumulation, and nitrate assimilation. In this study, a photoperiodic plastic global orchestration among transcriptome, proteome, and physiological dynamics was characterized to identify photoperiod-specific temporal offsets between the timing of transcripts, proteins, and physiological responses.
Urine toxicology screening reduces misdiagnosis of cocaine-induced ANCA positive disease as idiopathic granulomatosis with polyangiitis
Authors: Bateman James , Nadeem Mir , Barraclough James , Adizie Tochukwu , Pucci Mark , Sheeran Tom
Published: February 2025

Objectives

Study aims: (1) assess the impact of urine cocaine screening in distinguishing cocaine induced midline destruction lesion (CIMDL) from idiopathic ANCA-associated systemic vasculitis (AASV); (2) evaluate the adoption and effectiveness of screening; (3) explore its clinical implications.

Methods

We conducted a retrospective single-centre case series, reviewing rheumatology patients with suspected new or relapsing AASV aged 18–55, from April 2021-July 2024. Patients were in two groups-an active screening group offering urinary cocaine testing for all patients, and a standard care group, with ad-hoc testing based on clinical suspicion. Demographics, clinical presentations, and diagnostic pathways were analysed.

Results

Of 11 cases in the active screening group, all denied cocaine use, seven were diagnosed with CIMDL from urine screening, four patients were treated for vasculitis. In the standard care group of 15 patients, two CIMDL cases (admitted cocaine use), no patients had urine screening, 13 treated for AASV. In total nine CIMDL cases (mean age 38.2 years, IQR 11, six females), most (7/9; 78%) were from active screening. CIMDL presentations were heterogeneous including vocal cord palsy, lymphadenopathy and cutaneous vasculitis. CIMDL cases were positive for pANCA (6/9) and PR3 (7/9), with no MPO positivity, 5/9 (71%) failed to provide an adequate initial urine sample. There were no formal complaints or concerns from screening.

Conclusion

These data support the effectiveness and acceptability of systematic screening for cocaine to improve the identification of CIMDL, reducing misdiagnosis and unnecessary treatment. A protocol for systematic screening is proposed to improve the care for these patients.
Inhibitory Effect of Volatiles from Flavobacterium johnsoniae TR-18 on Aspergillus flavus Growth and Aflatoxin Production
Authors: Gong Andong , Liu Jingrong , Wang Gaozhan , Song Mengge , Wang Jianhua , Zhang Jingbo
Published: February 2025

Aspergillus flavus and the produced aflatoxins cause great damage to crop production, food security, and human health. The control of A. flavus and aflatoxins in the grains during storage is a great challenge to humans worldwide. In this study, we investigated the potential of the strain TR-18, isolated from the rhizosphere of tea plants, in controlling A. flavus and aflatoxins. The results demonstrated that TR-18 greatly inhibited A. flavus growth in dual cultural tests by the production of antifungal volatiles. TR-18 was identified as Flavobacterium johnsoniae through biochemical analysis and a 16S rRNA phylogenetic tree. Moreover, TR-18 effectively inhibited A. flavus growth and aflatoxin production in peanuts during storage. Further analysis of TR-18’s volatiles was conducted by gas chromatography–tandem mass spectrometry. Five authentic compounds were identified in the volatiles of TR-18: methyl thiolacetate, dimethyl disulfide (DMDS), methyl isovalerate, 5-methyl-3-hexanone, and S-methyl 3-methylbutanethioate. DMDS with a relative content of 54.92% (peak area normalization) was the most abundant compound in the volatiles. The minimal inhibitory concentration of DMDS against A. flavus growth was 50 μl/liter (compound volume/airspace volume). The other compounds also showed a great inhibition rate (more than 90%) to A. flavus at 200 μl/liter. In addition, TR-18 exhibited broad antifungal activity against other six important phytopathogens, that is, Fusarium graminearum, F. verticillioides, Colletotrichum graminicola, C. fructicola, Alternaria alternata, and Botrytis cinerea, with inhibition rates ranging from 52.90 to 98.70%. In conclusion, F. johnsoniae TR-18 with the production of five types of antifungal volatiles could be used as potential biocontrol agents in controlling pathogenic fungi and associated mycotoxins in the grains during storage.
ALZ‐801 prevents amyloid β‐protein assembly and reduces cytotoxicity: A preclinical experimental study
Authors: Muramatsu Daiki , Watanabe‐Nakayama Takahiro , Tsuji Mayumi , Umeda Kenichi , Hikishima Sadao , Nakano Hiroto , Sakashita Yasuhiro , Ikeda Tokuhei , Konno Hiroki , Kodera Noriyuki , Ando Toshio , Noguchi‐Shinohara Moeko , Ono Kenjiro
Published: February 2025

Alzheimer's disease (AD) is the most prevalent age‐related neurodegenerative disorder, mainly characterized by amyloid β (Aβ) accumulation in the brain. Numerous new agents are currently undergoing clinical trials as disease‐modifying therapies (DMTs) targeting Aβ. ALZ‐801 is a promising candidate DMT for AD, with a phase 3 trial of ALZ‐801 ongoing specifically for apolipoprotein E (APOE) ε4 homozygous patients with early‐stage AD. This study aimed to examine the effects of ALZ‐801 on Aβ assembly and explore its toxicological profile. Thioflavin T (ThT) assays and two imaging modalities—transmission electron microscopy (TEM) and high‐speed atomic force microscopy (HS‐AFM)—were used to evaluate ALZ‐801's effects on Aβ assembly. To assess the effect of ALZ‐801 on Aβ42‐induced cytotoxicity, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays and lactate dehydrogenase (LDH) assays were performed. ThT assays revealed increased lag time and decreased fluorescence in the presence of ALZ‐801, confirming inhibition of Aβ42 fibril formation, as confirmed by TEM. Real‐time observation using HS‐AFM revealed that ALZ‐801 inhibited the formation of Aβ42 fibril from low‐molecular‐weight (LMW)‐Aβ42 in the presence of Aβ42 seeds. HS‐AFM also revealed that globular aggregates from LMW‐Aβ42 were significantly larger with ALZ‐801, with few fibrils noted. MTT and LDH assays indicated that ALZ‐801 prevented LMW‐Aβ42‐induced cytotoxicity but did not reduce cytotoxicity induced by high‐molecular‐weight‐Aβ42. ALZ‐801 can inhibit Aβ42 aggregation by preventing both nucleus formation and fibril elongation, while promoting large globular oligomer formation, and can significantly reduce LMW‐Aβ42‐induced cytotoxicity. These findings underscore the potential of ALZ‐801 as an effective DMT for APOE ε4 homozygous patients with AD.
Whole‐body vibration protects against chronic high‐altitude hypoxic bone loss by regulating the nitric oxide/HIF‐1α axis in osteoblasts
Authors: Wang Dan , Liu Ruobing , Ding Yuanjun , Pei Qilin , Sun Tao , Shao Xi , Jiang Maogang , Liu Juan , Huang Jinghui , Yan Zedong , Hao Xiaoxia , Jing Da , Cai Jing
Published: February 2025

The hypobaric hypoxia environment found at high altitudes imposes various reversible and irreversible detrimental effects on living organisms. Accumulating evidence suggests that hypobaric hypoxia negatively impacts skeleton health by diminishing bone quality and disrupting bone microarchitecture. However, therapeutic strategies to counteract this bone loss remain limited. This study investigates the impact of whole‐body vibration (WBV) stimulation on skeletal health of rats continuously exposed to simulated hypobaric hypoxia environment at an altitude of 4500 m for 6 weeks. We found that WBV stimulation at 30 Hz and 0.3 g significantly improved femoral bone mass, microarchitecture, and biomechanical properties in rats exposed to chronic hypobaric hypoxia. Additionally, in vitro studies demonstrated that WBV enhanced osteogenic potential and activity in primary osteoblasts under hypoxia conditions. It also reduced levels of hypoxia‐inducible factor 1α (HIF‐1α), a key transcription factor involved in cellular response to hypoxia. Conversely, overexpression of HIF‐1α significantly inhibited cellular differentiation and osteogenesis in osteoblasts exposed to WBV stimulation under hypoxic conditions. Furthermore, WBV stimulation led to a significant increase in nitric oxide (NO) concentrations in osteoblasts during hypoxic exposure. In vitro experiments showed that blocking of NO synthesis with L‐NAME impeded WBV‐stimulated osteogenic activity in hypoxia‐exposed osteoblasts. In vivo studies demonstrated that inhibiting NO synthesis similarly abolished the positive impact of WBV on bone microarchitecture and biomechanical properties under hypobaric hypoxia. Collectivity, our findings indicate that WBV protects against hypobaric hypoxia‐induced bone loss by regulating the NO/HIF‐1α axis in osteoblasts, and reveal its clinical potential as a promising non‐invasive approach.
Self-Fitting Hearing Aids: Effects of Starting Response and Field Experience
Authors: Boothroyd Arthur , Sengupta Dhiman , Painter Shaelyn , Shur Elena , Garudadri Harinath , Mackersie Carol
Published: February 2025

Objectives:

To determine the effects of changing from a prescribed to a generic starting response on self-fitting outcome and behavior before and after a brief field experience.

Method:

Twenty adult hearing-aid users with mild-to-moderate hearing loss used a smartphone interface to adjust level and spectral tilt of the output of a wearable master hearing aid while listening to prerecorded speech, presented at 65 dB SPL, in quiet. A prescribed starting response was based on the participant’s own audiogram. A generic starting response was based on an audiogram for a typical mild-to-moderate hearing loss and was the same for all participants. Initial self-fittings from the two starting responses took place in the lab. After a brief field experience, involving conversation, self-hearing, and ambient noise, with readjustment as needed, self-fittings from the two starting responses were repeated in the lab. Starting responses, self-fitted responses, and adjustment steps were logged in the master hearing aid for subsequent evaluation of real-ear output spectra and for assessment of self-fitting behavior.

Results:

Neither starting response nor field experience had a significant effect on mean self-fitted output in the lab (p = 0.506 and 0.149, respectively). However, the SD of individual starting-response effects on high-frequency self-fitted output fell by around 50% after the field experience (p = 0.006). The effect of starting response on self-fitting behavior was limited to number of adjustment steps, which was higher for the generic start (p = 0.014). The effect of field experience on self-fitting behavior was limited to a 50% reduction in self-fitting time (p < 0.001). This reduction was attributable mainly to less time spent listening after each adjustment step (p = 0.019).

Conclusions:

The findings support the conclusion that, for a population with mild-to-moderate hearing loss, a generic starting response can be a viable option for over-the-counter self-fitting hearing aids. They highlight, however, the need for practice and experience with novel self-fitting hearing aids and the fact that self-fitting may not be suitable for all.
Long-term Economic Distress and Growing Educational Inequity in Life Expectancy
Authors: Geronimus Arline T. , Waidmann Timothy A , Bound John , Pancini Vincent , Yang Meifeng
Published: February 2025

Background:

The nature and timing of increasing educational inequity in US life expectancy prior to the COVID-19 pandemic suggests that long-term adverse labor market conditions secondary to globalization and technological change played a role for less-educated workers, but this has not been tested.

Methods:

We exploit spatiotemporal variation in mortality and long-term economic conditions at the year and commuting zone level to estimate the relationship between macroeconomic restructuring and diverging mortality trends, 1990-2017, by race, gender, and education. Our measure of macroeconomic restructuring is based on the baseline industrial mix of an area, a measure that is plausibly exogenous to mortality.

Results:

Mortality trends were substantially worse in commuting zones experiencing long-term economic stagnation than in others. For both White and Black adults, this relationship was strongest in the lowest quartile of the education distribution. Residence in commuting zones in the top quartile of our measure of economic conditions was associated with an additional 1-2 years lived between ages 25 and 84 compared to living in a commuting zone in the bottom quartile. The primary mediators of these divergent mortality trends were cancer, cardiovascular and metabolic diseases, and diseases of other internal body systems. Deaths from suicide or substance abuse did not contribute importantly toward accounting for the estimated impact of long-term economic stagnation on mortality.

Conclusions:

In our study, diverging trends in US life expectancy were associated with macroeconomic changes witnessed over the last half-century. The causes of death mediating this link were largely found in rates of death from stress-related internal diseases.
Efficacy of Mesh Use in Breast Surgery: A Comprehensive Review of Complications and Aesthetic Outcomes
Authors: Williams Sonya , Shauly Orr , Menon Ambika , Jolkovsky Eliana , Gould Daniel J. , Losken Albert
Published: February 2025

Background:

The insertion of a mesh “internal bra” has been used in cosmetic breast procedures for soft-tissue reinforcement as a means to mitigate postoperative ptosis. However, there have been concerns regarding complications as a result of mesh placement and a lack of quantitative data regarding postoperative cosmetic outcomes.

Methods:

Articles that assessed the effects of the mesh internal bra for soft-tissue support on cosmetic and patient-reported outcomes, complications, and surveillance were reviewed. Meta-analysis was performed to determine the overall complication rates, and cosmetic outcomes and patient-reported outcomes were reviewed.

Results:

Meta-analysis showed the following summary effect sizes: infection/abscess had a pooled rate of 3.61% (Q = 33.8, I
2 = 76.33%), hematoma was 1.34% (Q = 4.16, I
2 = 68.1%), seroma was 5.04% (Q = 14.8, I
2 = 73.11%), fat necrosis was 0.86% (Q = 693, I
2 = 99.7%), and capsular contracture was 2.5% (Q = 693.4, I
2 = 99.6%). Only 2 of 5 studies attempting to quantify cosmetic outcomes compared outcomes between patients who underwent procedures with and without the use of mesh. Both reported smaller increases in sternal notch-to-nipple distance and nipple-to-inframammary fold distance without clear statistical significance.

Conclusions:

Although there does not seem to be a significant difference in risk profile with and without the use of mesh, the current data do not support the claims of improved cosmetic outcomes. Well-controlled, quantitative studies are necessary to objectively evaluate the cosmetic benefits of using mesh.
Longitudinal Visual Outcomes and Risk of Papilledema Recurrence in Fulminant Idiopathic Intracranial Hypertension
Authors: Shaia Jacqueline K. , Rock Jenna R. , Chu Jeffrey Y. , Trinh Ilene P. , Alam Taseen A. , Singh Rishi P. , Talcott Katherine E. , Cohen Devon A.
Published: February 2025

Background:

Fulminant idiopathic intracranial hypertension (IIH) is a rare presentation of IIH characterized by rapid visual loss. Little is known regarding the cause of fulminant IIH and how to treat this condition. We conducted an analytical study aimed at characterizing disease, treatment, and visual outcomes while evaluating the time and frequency of recurrence of papilledema.

Methods:

This retrospective cohort study used records at a single tertiary institution screened between June 1, 2012, and September 31, 2023, for having an international classification of diseases (ICD) code of IIH or papilledema. After meeting the revised Dandy diagnostic criteria and excluding secondary causes of IIH using clinical review, fulminant IIH was determined by rapid visual loss occurring within 1 month of symptom onset. Demographics, treatment, and visual outcomes data were collected with final visual outcomes reported between 3 months and 1 year after diagnosis. Surgical intervention and relapse of papilledema were noted. All analyses were performed in R Studio and Excel, with a P value <0.05 being significant.

Results:

Of the 731 IIH patients who were evaluated during this interval, 3.2% had fulminant IIH (n = 24). Patients had a mean age of 27.6 years and presented with an average visual field mean deviation of −19.55 dB. Overall, 95.8% were overweight/obese, 87.5% female, and 50% were Black. In total, 62.5% of patients with fulminant IIH received optic nerve sheath fenestrations. At follow-up, 41.7% of patients were legally blind (with 20/400 vision or worse), including 13% having no light perception. Within our cohort, 42% had a significant visual deficit (visual field mean deviation worse than -7 dB or best-corrected visual acuity between 20/80 and 20/200). Although not statistically significant, patients who underwent cerebral venous sinus stenting had the smallest visual deficit. On average, patients recovered from their initial papilledema after 7.90 months. One quarter (25%) of patients had a recurrence at 4.5 months (SD ± 4.1) after the initial resolution of papilledema.

Conclusions:

Fulminant IIH is a rare and blinding variant of IIH. Owing to the recurrence time after initial papilledema resolution, we recommend all such patients be monitored until 8 months after initial papilledema resolution. Future studies should evaluate optimal surgical interventions for preserving vision.
Updating the PRISMA reporting guideline for network meta-analysis: a scoping review
Authors: Veroniki Areti Angeliki , Tricco Andrea C. , Rangira Daniella , McKenzie Joanne E. , Li Tianjing , Straus Sharon E. , Smith Maureen , Catalá-López Ferrán , Wolfe Dianna , Nincic Vera , Konstantinidis Menelaos , Franco Juan , Tovey David , Thirugnanasampanthar Sai Surabi , Dourka Jasmeen , Warren Rachel , Wells George , Stevens Adrienne , Hutton Brian
Published: February 2025

STANDFIRST

This scoping review represents the initial step in updating the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) extension for network meta-analysis (NMA) to improve the usability and relevance of systematic reviews with NMA for diverse audiences. The update will address gaps in reporting, such as documenting methods for assessing NMA homogeneity and transitivity, defining intervention nodes, and considering advances in statistical modeling. It will align with PRISMA 2020 and incorporate input from diverse knowledge users, including patients and the public. This scoping review included 61 studies, comprising 23 guidance documents and 38 overviews of reviews evaluating the completeness of reporting and methodological quality of published NMAs. We identified 37 additional NMA items for inclusion in the next step—the Delphi survey. Building on a 2014 scoping review by our team, we incorporated recent studies to inform the PRISMA-NMA update, adhering to established standards for guideline development.

SUMMARY POINTS

Network meta-analyses (NMAs) are increasingly prominent in evidence synthesis, but their methodological transparency and reporting completeness remain inconsistent, which affects the reliability of results.

This scoping review highlights the need to update PRISMA-NMA to address evolving methodologies (e.g., component NMA) and reporting challenges to improve accessibility and utility of NMA findings.

The review underscores progress and gaps in NMA reporting since the 2015 PRISMA-NMA extension, focusing on synthesis methods, homogeneity, consistency and transitivity assessments, and network geometry.

Key recommendations, such as defining pre-specified nodes, specifying statistical methods, and addressing competing interests, were often overlooked in NMA reporting, but addressing these gaps could enhance transparency, reproducibility, and trust in NMA results.
Generation of machine-learning derived Cancer Vulnerability Indicator to determine the spatial burden of cancer outcomes
Authors: Kou Kou , Cameron Jessica , Dasgupta Paramita , Chen Hao , Baade Peter D
Published: February 2025

Background

Due to the difficulty of obtaining population-based individual-level data, ecological studies are often used to explore factors related to geographic variations in health outcomes. This study proposes a novel framework to identify area-level predictors of spatial variations in lung cancer outcomes and generate a lung cancer vulnerability index (LcVI) based on these predictors.

Methods

Data on 11,313 persons diagnosed with invasive lung cancer in Queensland, Australia (2016-2019) were sourced from the population-based Queensland Cancer Register. Bayesian spatial models estimated smoothed standardised incidence ratios (SIRs) for 519 geographic areas. Area-level variables (n= 911) were extracted from multiple data collections. Random forest models were fitted to identify important predictors for lung cancer incidence rates. A novel non-parametric dimensionality reduction approach incorporating the final random forest model results was developed to generate the LcVI which ranged from 0-10.

Results

Eight variables were identified as predictors for lung cancer incidence with the top two being the prevalence of diabetes and adequate fruit intake. Areas having incidence rates below the Queensland average had significantly lower LcVI than those with average incidence rates (mean difference = 2.80, 95% CI: 2.34-3.25, p < 0.001) while areas with above average incidence rates had significantly higher LcVI than those with average incidence (mean difference = 2.70, 95% CI: 2.20-3.19, p < 0.001). The LcVI was strongly associated with the continuous SIR, explaining 57% of the variation (R² = 0.57, p< 0.001).

Conclusion

This novel approach identified a small number of important predictors for lung cancer incidence from a high-dimensional dataset. The lung cancer vulnerability index based on these predictors effectively explained the geographic variations in incidence, potentially offering insights into the underlying drivers of these variations. The favourable performance of this approach may promote further ecological studies on other cancer outcomes.
A summary of intraspecific size variation for large mysticetes
Authors: McClure Joseph
Published: February 2025

Following existing work on odontocetes, an extensive survey of literature was conducted to summarize the growth and body mass of nine mysticete species along with analyses of adult size distributions using data from the International Whaling Commission catch database. Relationships uncovered between adult length parameters in mysticetes are combined with results previously obtained for odontocetes. On average, the mean adult length was 4% below the asymptotic size and its relative variation appeared to be very similar across most species (CV=4-5%), though is notably higher in species with more prolonged growth throughout adulthood (CV=6-8%). Total body mass relationships between mysticete species appear to align with feeding strategies, as generalists and skim-feeders are notably heavier than lunge-feeding specialists.
Analysis of blood-based DNA Methylation signatures of aging and disease progression in IBD patients
Authors: Doherty Trevor , McDermott Edel , Delany Sarah Jane , Mulcahy Hugh , Murphy Therese
Published: February 2025

Background: Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a dysregulated immune response partly influenced by environmental factors. DNA methylation (DNAm), a key epigenetic mechanism, is implicated in the etiology of complex diseases, including IBD. Epigenetic clocks, which use DNAm patterns to estimate biological aging, have been increasingly linked to various health and disease states. Previous studies have associated DNAm with IBD, and first- and second-generation epigenetic clocks with IBD subtypes. Results: In a discovery IBD cohort (n=149) with 8-year clinical follow-up data, we explored the relationship between DNAm variation, second- and third-generation epigenetic clocks, and IBD clinicopathological outcomes, including disease subtype, activity, and recurrence. One CpG site was significantly differentially methylated (Benjamini-Hochberg adjusted p-value<0.05) in patients with clinical recurrence of disease over the long term (i.e., after the first year of study) compared to non-recurrence (no treatment escalation after 8 years). Next, we assessed DNAm aging signatures and IBD outcomes using logistic regression. Individuals with IBD exhibited significantly increased epigenetic aging, as measured by GrimAge, GrimAge2, and DunedinPACE, compared with controls. These associations were replicated in two independent IBD cohorts (GSE87648 (n=377) and GSE112611 (n=238)). Additionally, in UC patients, the active disease group was associated with higher age acceleration (GrimAge (U=669, p=0.003)) and higher pace of aging (DunedinPACE (t=3.233, 0.002)) compared to the inactive group. In the discovery cohort, DunedinPACE outperforms CRP measures in discriminating activity in UC patients with an AUC, sensitivity and specificity of 0.71, 69.5% and 68.7% respectively, highlighting its potential as a useful biomarker of activity in UC. Conclusions: Overall, we present strong evidence that dynamic age-related DNAm changes can be used to differentiate between IBD (including separately by subtype) and controls. Furthermore, our study provides important new evidence that DunedinPACE may have utility as a biomarker for monitoring disease recurrence in IBD patients and may be a strong marker of disease activity in UC patients. Overall, this suggests that blood-based DNAm signatures could serve as biomarkers for detection and monitoring of IBD.
In situ generated vaccine-like pyroptosome for personalized cancer immunotherapy
Authors: Chen Binlong , Wan Fangjie , Xia Heming , Pan Xingquan , Wang Letong , Wang Yaoqi , Yan Yue , Liu Jianxiong , Tang Mingmei , Yang Ye , Qin Mengmeng , Ren Jiaona , Zhong Lijun , Chen Wei , Zhang Qiang , Wang Yiguang
Published: February 2025

The efficacy of in situ cancer vaccination has been hampered by poor spatiotemporal orchestration of multiple key steps of cancer-immunity cycle in most tumours and systemic toxicity related to therapeutic strategies. Here, we report a systemic injectable and pyroptosis-enabled nanoadjuvant (SPEN) that precisely evokes the secretion of vaccine-like pyroptosome in tumour area for eliciting robust anti-tumour immunity. SPEN induces vigorous immunogenic pyroptosis, triggering the efficient release of tumour antigen-rich pyroptosomes, DAMPs, and proinflammatory cytokines. Upon the activatable release of a TLR7/8 agonist into pyroptosome, the generated pyroptosome functions as in situ cancer vaccine for cooperatively activating the cancer-immunity cycle while avoiding systemic toxicity. This in situ vaccine boosts both innate and adaptive immune response, facilitating the eradication of primary tumour and long-lasting cancer prevention. Our findings provide new insights into the rational design of pyroptosis-inducing nanomedicines for boosting the cancer-immunity cycle, thus advancing personalized cancer immunotherapy.
Fixation shifts in a novel “no-report” binocular rivalry paradigm induce saccade-related perceptual switches
Authors: Kingir Ege , Segawa Ryo , Hesse Janis K. , Kagan Igor , Wilke Melanie
Published: February 2025

No-report paradigms help to avoid report-related confounds in conscious perception studies. A novel no-report binocular rivalry paradigm by Hesse and Tsao (2020) tracks conscious content using eye position as subjects follow fixation points linked to the rivaling stimuli. However, it remains unclear whether perceptual changes arise spontaneously or are induced by external factors such as fixation shifts and saccades. We found an increased probability of perceptual switches time-locked to fixation point shifts, indicating that some switches are externally driven. To disentangle the effects of visual fixation shifts and saccades, we implemented a two-factorial design and found that saccades play a larger role in eliciting perceptual changes. We estimate that 14% of saccades trigger a switch, accounting for 24% of all perceptual transitions. Our findings provide an analysis framework and guidelines for excluding externally driven perceptual switches, enabling a clearer focus on internally generated perceptual dynamics.
Calcium channel-coupled transcription factors facilitate direct nuclear signaling
Authors: Rao Eshaan R. , Thaxton Tyler , Gama Eric , Godfrey Jack , Wei Cenfu , Lin Qiaoshan , Li Yan , Hejazi Pastor Daniel Parviz , Hansel Christian , Du Xiaofei , Gomez Christopher M.
Published: February 2025

VGCCs play crucial roles within the CNS, in maintaining cell excitability, enabling activity- dependent neuronal development, and forming long-term memory by regulating Ca2+influx. The intracellular carboxyl-terminal domains of VGCC α1 subunits help regulate VGCC function.

Emerging evidence suggests that some VGCC C-termini have functions independent of channel gating and exist as stable proteins. Here, we demonstrate that all VGCC gene family members express bicistronic mRNA transcripts that produce functionally distinct C-terminal proteins (CTPs) in tandem with full-length VGCC α1 subunits. Two of these CTPs, α1CCT and α1ACT, cycle to and from the nucleus in a Ca2+- and calmodulin-dependent fashion. α1CCT, α1ACT, and α1HCT regulate chromatin accessibility and/or bind directly to genes, regulating gene networks involved in neuronal differentiation and synaptic function in a Ca2+-dependent manner. This study elucidates a conserved process of coordinated protein expression within the VGCC family, coupling the channel function with VGCC C-terminal transcription factors.
A Pre-Bilaterian Origin of Phototransduction Genes and Photoreceptor Cells
Authors: Aleotti Alessandra , Giorgini Flaviano , Feuda Roberto
Published: February 2025

The evolution of vision is a major novelty in animals, playing a fundamental role in developing complex behaviours. Vision initiates with a light-triggered phototransduction cascade occurring in photoreceptor cells (PRCs). The two main PRC types, ciliary and rhabdomeric, employ both specific and common genes for phototransduction. Despite being crucial for vision, the origin and evolution of photoreceptor cells and phototransduction pathways remain unclear.

Using phylogenetic methods, we studied the evolution of all phototransduction genes, elucidating their gene duplication patterns in over 80 species, including non-bilaterian metazoans and other eukaryotes. Then, we investigated the expression of phototransduction genes in available single-cell RNA-sequencing data from various animals, including non-bilaterians. By using phototransduction genes as markers, we identified putative photoreceptor-like cells across animals and compared their regulatory toolkits.

Gene families encoding phototransduction components are generally ancient, predating the origin of vision. However, many phototransduction genes originated in the metazoan stem group. Moreover, putative photoreceptor cells identified in non-bilaterians appeared to express some but not all components of the two well-characterised phototransduction pathways, suggesting potential lineage-specific components involved in phototransduction. Finally, we identified conserved expression of certain transcription factors in putative PRCs in non-bilaterians, suggesting the homology of PRCs.
KYLO-0603, a novel liver-targeting, thyroid hormone receptor-β agonist for the treatment of MASH
Authors: lu Xueqin , Wang Shengjun , Du Yanchun , Xie Bixian , Chen Qingyan , Lin Jinzhen , Chen Bailing , Cui Kunyuan
Published: February 2025

Metabolic dysfunction–associated steatohepatitis (MASH) is a progressive liver disease associated with liver-related complications and death. Kylo-0603 is a novel agonist for the thyroid hormone receptor β (THR-β) that has been developed by merging the structures of three acetylgalactosamine (GalNAc)-modified ASPGR ligands with a triiodothyronine (T3) analog. This unique design allows for both THR-β activation and targeted delivery to hepatocytes, significantly reducing the risk of adversed effects related to increased systemic thyroid hormone-like effects. Additionally, it effectively lowers serum cholesterol by as much as 69.2% and low-density lipoprotein cholesterol (LDL-C) levels by up to 88.2% in the MASH mouse model. Meanwhile, Kylo-0603 was shown to reduce steatosis by up to 1.3 points (P < 0.001), inflammation by 1.8 points (P < 0.0001), and ballooning by 0.8 points (P < 0.01). The non-alcoholic steatohepatitis (NASH) activity score (NAS) decreased by up to 3.7 points (P < 0.0001), and the fibrosis score dropped by 0.6 points (P < 0.05). These findings suggest that Kylo-0603 is effective in enhancing liver tissue NASH status and inhibiting fibrosis progression. In summary, Kylo-0603, as a highly both tissue and target selective and low-toxicity THR-β agonist, shows significant promise for treating MASH and is likely to emerge as a new therapeutic option for patients with this condition.
Disruptions in Outer Membrane-Peptidoglycan Interactions Enhance Bile Salt Resistance in O-antigen-ProducingE. coli
Authors: Qin Jilong , Hong Yaoqin , Vollmer Waldemar , Morona Renato , Totsika Makrina
Published: February 2025

Bile salts (BS) are derived from cholesterol in the liver and act as antimicrobial agents in the intestines by disrupting bacterial cell membranes and inducing oxidative stress. The gut bacteriumE. coliis naturally resistant to BS, including the model strain K12 that produces a truncated LPS without O-antigen (OAg). Paradoxically, restoring a wild-type like LPS with OAg sensitisesE. coliK12 to exogenous BS. In this study, we investigate this phenomenon. We show that mutations causing truncation of the LPS core oligosaccharide render these strains even more susceptible to BS, similar to the mutant strain MG1655-SΔwaaLdefective in OAg ligase, primarily due to the accumulation of the lipid-linked intermediate UndPP-OAg. Through the characterisation of BS-resistant suppressor mutants of MG1655-SΔwaaL, we identify key genetic disruptions involved in resistance. Notably, we observed the highest BS resistance in strains with a weaker connection between the outer membrane (OM) and peptidoglycan (PG), including strains lacking the major OM-anchored, PG-binding proteins OmpA or Lpp, or expressing versions of these that lack PG-binding. Our data suggest that BS-induced stress in OAg-producingE. coliis due to the spatial constraints between OM and PG, and that mutations disrupting OM-PG interactions alleviate this stress, enhancing BS resistance. These findings provide new insights into a major challengeE. colifaces in the gut environment where it needs to produce OAg for stable colonisation and resists BS.E. colican only survive BS exposure by fine-tuning the connectivity between its cell envelope layers, which highlights a potential target for modulating bacterial responses to BS in the gut.

Author summary

Enteric bacteria residing in the human gut must withstand the host-derived antimicrobial agents, bile salts (BS), but the underlying resistance mechanisms are not fully elucidated. This study investigates the BS resistance mechanisms in O-antigen (OAg)-producingEscherichia coliK-12. We show that truncation of lipopolysaccharide (LPS) core oligosaccharides or restoration of OAg production increases BS sensitivity due to the accumulation of UndPP-OAg intermediates. By analysing suppressor mutants, we identify key genetic disruptions, particularly affecting the level of outer membrane-peptidoglycan (OM-PG) interactions involving OmpA and Lpp, which confer heightened BS resistance. Our findings highlight how BS-induced stress is linked to spatial constraints between the OM and PG layer, offering new insights into bacterial adaptation to BS stress. This research may provide new targets for therapeutic interventions to modulate gut microbial responses to BS.
DiatomNet: An automatic Diatom genus identification system through microscopic images and Deep Learning
Authors: Villar Pedro , Casado Jacobo , Fernández David , Sánchez Pedro , Tabik Siham
Published: February 2025

Diatoms are microscopic organisms belonging to the algae kingdom. They adapt to the ecosystem and modify their shape and texture depending on hundreds of ecosystem variables. Hence, these micro-organism are considered as the most accurate indicator to measure water quality. Commonly, the recognition of the class of diatoms in a microscopic image has always been done by expert biologists knowledgeable about the morphometric characteristics of these organisms. This work proposes a new automatic diatom genus recognition system from microscopic images using state-of-the-art deep CNNs. In particular, 1) we developed a public high quality database organized into 44 genus-level diatom classes, 2) designed a robust diatom classification model, and 3) provided a user-friendly interface to utilize our automatic diatom recognition tool.
Tiny killers: first record of rhabdocoel flatworms feeding on water flea embryos
Authors: Tüzün Nedim , Lemke Nina , Diez Yander L. , Artois Tom , Monnens Marlies
Published: February 2025

Flatworms are increasingly recognized for their ecological significance and potential to disrupt local fauna, yet most research has focused on conspicuous, larger planarians. Smaller flatworms, or microturbellarians, are often top predators within meiofaunal food webs. Here, we report a novel interaction involving a rhabdocoel microturbellarian,Strongylostoma simplex, predating onDaphniawater flea embryos. We identified the flatworm based on histological serial sections and recognized key diagnostic traits. In a laboratory experiment, we tested for survival and offspring production ofDaphnia magnain the presence and absence ofStrongylostoma simplex. Exposure to flatworms caused a drastic reduction in water flea fitness, indicated by the strongly reduced survival and offspring production in flatworm-exposedDaphnia. This finding corroborates our visual observations of egg predation by these flatworms, and suggests a strong pressure onDaphniapopulation dynamics. This is particularly concerning for small or isolated water bodies, such as the water reservoirs located in a cemetery in Berlin in which we documented this interaction, as this would increase the probability of encounters between flatworms and water fleas. AsDaphniaplay an essential role in regulating phytoplankton blooms and supporting higher trophic levels in freshwater ecosystems, understanding the ecological consequences of potentially invasive predatory flatworms is imperative.
Brain bases for navigating acoustic features
Authors: Billig Alexander J. , Sedley William , Gander Phillip E. , Kumar Sukhbinder , Lad Meher , Chait Maria , Mohammadi Yousef , Berger Joel I. , Griffiths Timothy D.
Published: February 2025

Whether physical navigation shares neural substrates with mental travel in other behaviourally relevant domains is debated. With respect to sound, pure tone working memory in humans elicits hippocampal as well as auditory cortical and inferior frontal activity, and rodent work suggests that hippocampal cells that usually track an animal’s physical location can also map to tone frequency when task-relevant. We generated a sound dimension based on the density of random-frequency tones in a stack, resulting in a percept ranging from low- (“beepy”) to high-density (“noisy”). We established that unlike tone frequency, which listeners automatically associate with vertical position, this density dimension elicited no consistent spatial mapping. During functional magnetic resonance imaging, human participants (both sexes) held in mind the density of a series of tone stacks and, after a short maintenance period, adjusted further stacks to match the target (“navigation”). Density was represented most strongly in bilateral non-primary auditory cortex, specifically bilateral planum polare. Encoding and maintenance activity in hippocampus, inferior frontal gyrus, planum polare and posterior cingulate was positively associated with subsequent navigation success. Bilateral inferior frontal gyrus and hippocampus were among regions with elevated activity during navigation, compared to a parity-judgment condition with closely matched acoustics and motor demands. Bilateral orbitofrontal cortex was more active when navigation was toward a target density than when participants adjusted density in a control condition with no particular target. We find that self-initiated travel along a non-spatial auditory dimension engages a brain system overlapping with that supporting physical navigation.

Significance Statement

Work in rodents suggests that navigation in physical space and the active analysis of sounds share a neural substrate in the hippocampus, supporting the use of common computational mechanisms. We examined the human brain system for navigation through an acoustic environment to a remembered target. In addition to high-level auditory cortex we demonstrate involvement of the hippocampus along with sites in frontal and cingulate cortex that also support physical navigation.