bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Pediatric Age-Based and Weight-Adjusted Nomogram for Bladder Volumes Associated With Successful Completion of Transabdominal Pelvic Ultrasound (TPU)
Authors: Drayna Patrick C. , Johnson Cameron , Chinta Sri S. , Jaafar Hayder , Thomas Danny , Visotcky Alexis , Dupont Amanda S. , Kumbhar Sachin
Published: February 2025

Objective:

To develop a nomogram for pediatric bladder volumes associated with the successful completion of transabdominal pelvic ultrasound (TPU) in female pediatric patients presenting with lower abdominal and/or pelvic pain in the emergency department. This study hypothesizes that the target bladder volumes for successful TPU vary by age and weight.

Methods:

We retrospectively calculated bladder volumes on all successful transabdominal pelvic ultrasound studies during a 2-year period for patients 8 to 18 years old by ellipsoid bladder volume formula using the largest cross-sectional areas captured on transverse and longitudinal cine clips. Measurements were collected by 2 study personnel with initial measurements validated by a pediatric radiologist. Bladder volume by age and weight percentile groups were descriptively analyzed, and a quantile regression model was used to regress bladder volume on age adjusting for patient weight.

Results:

We analyzed bladder volumes from 1030 successful transabdominal pelvic ultrasound studies. The greatest drop in median volume was seen amongst non-overweight children in younger age groups. Nomogram bladder volumes for transabdominal pelvic ultrasound increase consistently with age and weight until approximately 13 years old and 60 kg, respectively, with minimal change thereafter in patients 13 to 18 years old.

Conclusions:

We provide a pediatric age-based and weight-adjusted nomogram for bladder volumes associated with successful transabdominal pelvic ultrasound imaging. Further evaluation of its use is warranted to decrease inefficiency in bladder filling prior to TPU completion and improve timeliness in diagnosing pelvic emergencies.
Preferences for Care Among African American Women Considering Postmastectomy Breast Reconstruction
Authors: Shammas Ronnie L. , Hung Anna , Ramkalawan Janel , Mullikin Alexandria , Moore Angelo , Greenup Rachel A. , Hollenbeck Scott T. , Phillips Brett T. , Matros Evan , Reed Shelby D. , Lee Clara N.
Published: February 2025

Background:

Approximately 20% of patients report inadequate discussions with their providers about reconstructive options, with an increased frequency reported in non-White women. Eliciting treatment preferences with adaptive choice-based conjoint (ACBC) analysis can improve our understanding of what patients’ value. We aimed to determine what African American (AA) patients value when considering breast reconstruction options.

Methods:

Cross-sectional ACBC with AA women considering breast reconstruction recruited through community partnerships and an academic medical center. Relative importance scores, part-worth utilities, and maximum-acceptable risks were calculated to assess preferences for attributes of flap versus implant reconstruction.

Results:

Overall, 181 women, 101 from an academic center and 80 from the community were included. The most important attributes were risk of complications [mean (SD) relative importance (RI), 26% (12%)], additional surgeries [RI, 24% (14%)], and abdominal morbidity [RI, 22% (11%)]. Women were least concerned with appearance [RI, 15% (12%)] and recovery time [RI, 14%, (10%)]. Fewer women preferred a profile representing flap (n=27, 15%) compared to implant reconstruction (n=154, 85%). Those who preferred flap reconstruction cared most about additional surgeries [RI, 36% (15%)]; in contrast, those who preferred implant reconstruction cared most about complications [RI, 27% (12%)]. Participants with fewer comorbidities [OR, 0.84; p=0.012], no prior surgical complication (OR, 0.32; p=0.029), and prophylactic mastectomy (OR, 6.07; p=0.19) were more likely to choose the implant profile.

Conclusion:

AA patients place greatest value on minimizing complication risk and additional surgeries when considering post-mastectomy reconstruction. Future studies should assess how eliciting individual-level preferences can improve shared decision-making in surgery.
Trait Impulsivity Predicts Treatment Response in Gambling Disorder
Authors: Chamberlain Samuel R. , Ioannidis Konstantinos , Grant Jon E.
Published: February 2025

Objectives

Impulsivity is thought to be a core feature of gambling disorder, yet little is known as to whether trait impulsivity predicts treatment response.

Methods

Data were pooled from 2 previous randomized controlled pharmacological trials using naltrexone and N-acetyl cysteine.

Results

Trait impulsivity statistically explained variation in medication treatment response (P = 0.0260, R
2 = 0.26). Higher baseline motor impulsiveness was associated with greater treatment response (P = 0.009).

Conclusions

Measures of impulsivity may thus be important to include in future large-scale datasets, in trial settings but also routine clinical gambling clinic practice, toward building predictive algorithms that may ultimately help to inform optimal treatment choices and improve outcomes.
DNA sequencing of whole human cytomegalovirus genomes from formalin-fixed, paraffin-embedded tissues from congenital cytomegalovirus disease cases
Authors: Li Kathy K. , Suárez Nicolás M. , Camiolo Salvatore , Orton Richard J. , Davison Andrew J.
Published: February 2025

Background

Congenital cytomegalovirus disease (cCMV) can be severe but is uncommon. Investigations of the role of genome sequence variation in the causative virus (human cytomegalovirus, HCMV) in clinical outcome have to date depended on small sample numbers derived from fresh tissues. Extensive formalin-fixed, paraffin-embedded (FFPE) cCMV biorepositories established worldwide potentially provide much larger sample numbers for future investigations. However, there are no published reports of sequencing whole HCMV genomes from such material.

Objective

To sequence whole HCMV genomes from cCMV FFPE material.

Study design

Sixteen FFPE samples of foetal kidney or placental tissue were processed from ten cCMV cases in foetuses or neonates. Two commercial kits for extracting DNA from FFPE material were evaluated, HCMV DNA was enriched in the extracts, and the samples were sequenced on the Illumina platform. The sequence read datasets were analysed by genotyping, genome assembly and variant calling using a published software pipeline.

Results

Whole HCMV genomes were sequenced for five cases using either DNA extraction kit.

Conclusions

Sequencing whole HCMV genomes from cCMV FFPE material is feasible. This potentially facilitates future studies of the effects of HCMV variation on the clinical outcome of cCMV.

Highlights

Human cytomegalovirus (HCMV) causes congenital cytomegalovirus disease (cCMV).

cCMV samples exist in formalin-fixed, paraffin-embedded (FFPE) biorepositories.

Sequencing whole HCMV genomes from such material is feasible.

This may aid future studies on the effect of HCMV diversity on cCMV outcomes.
Understanding motivations of older women to continue or discontinue breast cancer screening
Authors: Weller Susan C. , Pappadis Monique R. , Krishnan Shilpa , Stearnes Marsja R. , Sheffield Kristin M. , Tan Alai , Qi Jeffrey Z. , Goodwin James S.
Published: February 2025

Background

Breast cancer screening guidelines indicate screening in women over 75 years of age is optional, depending upon patient health and preferences.

Objectives

To link experiences and perceptions of older women concerning screening to their intention to continue or discontinue screening.

Design

Qualitative comparative study, comparing continuers and discontinuers.

Setting

Community-residing adults.

Participants

A purposive sample (n=59) with equal representation of White, Black, and Hispanic women by age (70-74 years and 75 and older) and educational level (≤12 grade and >12 grade).

Measurements

In-depth qualitative interviews explored women’s perceptions of mammograms, the benefits and risks of screening, and personal screening experiences. Interviews were coded and quality-checked by two or more coders. A qualitative comparative analysis (QCA) was used to identify combinations of personal characteristics and themes linked to the intention to continue (n=32) or discontinue (n=27) screening.

Results

Personal experience themes were strongly linked to the intention to continue or discontinue. Women who mentioned recent screening (within three years) and either a spontaneously mentioned cancer story concerning a friend or family member or a doctor’s screening recommendation intended to continue screening (91% true positive rate, model sensitivity). Women who did not schedule screening and who did not mention a cancer story or a doctor’s recommendation (or neither) intended to discontinue screening (81% true negative rate, model specificity). These themes transcended differences in race/ethnicity, age, and educational level.

Conclusion

Continuation of breast cancer screening in older women is motivated by their personal screening history combined with cancer experiences and/or a doctor’s screening recommendation.
Characterization of RNA cargo from extracellular vesicles obtained from cerebrospinal fluid and plasma samples in schizophrenia participants and healthy volunteers
Authors: Gallego Juan A. , Palade Joanna , Alsop Eric , Hutchins Elizabeth , Hsieh Michael , Logerman Amber , Bilagody Cherae , Reiman Rebecca , Meechoovet Bessie , Terraf Panieh , Beecroft Blake , Janss Alex , Gallaso Francesca , Whitsett Timothy G. , Blanco Emily A. , Lencz Todd , Keuren-Jensen Kendall Van , Malhotra Anil K.
Published: February 2025

Biomarkers that are clinically useful for the diagnosis and treatment of schizophrenia are lacking. Biomarkers are critical tools that reduce the incidence of misdiagnosis, identify subgroups of patients, assist in the proper characterization of patient phenotypes, predict response to treatment or the development of side effects, and can serve as targets for novel therapeutic interventions. In this study, we evaluated small (< 200 nucleotide) and long (> 200 nucleotide) RNAs found in extracellular vesicles (EVs) isolated from the cerebrospinal fluid (CSF) and plasma of individuals with schizophrenia spectrum disorders (SSD) and healthy volunteers (HV). As EVs carry cargo from all tissues in the body, they act as a potential proxy for the tissue of origin, including cells from the brain. We compared the transcriptomic features of EVs from these two biofluids and examined their ability to discriminate between SSD and HV participants, identifying a total of 141 differentially expressed genes, some of which have been previously associated with SSD. Next, we evaluated the potential cell-types that give rise to the SSD-associated CSF RNA cargo, and found the majority were predominantly expressed in excitatory neurons. Our results highlight the potential of EVs as both a source of schizophrenia relevant biomarkers, and molecular insight into disease mechanisms.
Language Model Applications for Early Diagnosis of Childhood Epilepsy
Authors: Loyens Jitse , Slinger Geertruida , Doornebal Nynke , Braun Kees P.J. , Otte Willem M. , van Diessen Eric
Published: February 2025

Objective

Accurate and timely epilepsy diagnosis is crucial to reduce delayed or unnecessary treatment. While language serves as an indispensable source of information for diagnosing epilepsy, its computational analysis remains relatively unexplored. This study assessed – and compared – the diagnostic value of different language model applications in extracting information and identifying overlooked language patterns from first-visit documentation to improve the early diagnosis of childhood epilepsy.

Methods

We analyzed 1,561 patient letters from two independent first seizure clinics. The dataset was divided into training and test sets to evaluate performance and generalizability. We employed two approaches: an established Naïve Bayes model as a natural language processing technique, and a sentence-embedding model based on the Bidirectional Encoder Representations from Transformers (BERT)-architecture. Both models analyzed anamnesis data only. Within the training sets we identified predictive features, consisting of keywords indicative of ‘epilepsy’ or ‘no epilepsy’. Model outputs were compared to the clinician’s final diagnosis (gold standard) after follow-up. We computed accuracy, sensitivity, and specificity for both models.

Results

The Naïve Bayes model achieved an accuracy of 0.73 (95% CI: 0.68-0.78), with a sensitivity of 0.79 (95% CI: 0.74-0.85) and a specificity of 0.62 (95% CI: 0.52-0.72). The sentence-embedding model demonstrated comparable performance with an accuracy of 0.74 (95% CI: 0.68-0.79), sensitivity of 0.74 (95% CI: 0.68-0.80), and specificity of 0.73 (95% CI: 0.61-0.84).

Conclusion

Both models demonstrated relatively good performance in diagnosing childhood epilepsy solely based on first-visit patient anamnesis text. Notably, the more advanced sentence-embedding model showed no significant improvement over the computationally simpler Naïve Bayes model. This suggests that modeling of anamnesis data does depend on word order for this particular classification task. Further refinement and exploration of language models and computational linguistic approaches are necessary to enhance diagnostic accuracy in clinical practice.
Characteristics of a tattooed population and a possible role of tattoos as a risk factor for chronic diseases: Results from the LIFE-Adult-Study
Authors: Theune Loryn E. , Ghoreishi Narges , Müller-Graf Christine , Engel Christoph , Wirkner Kerstin , Baber Ronny , Laux Peter , Luch Andreas , Giulbudagian Michael
Published: February 2025

Tattoos and permanent make-up (PMU) gain increasing popularity among the general population. There are indications that pigments or their fragments may translocate within the body, however knowledge about possible systemic adverse effects related to tattoos is very limited. We investigated the prevalence of systemic chronic health effects including cardiologic diseases, cancer and liver toxicity and their relationship with the presence and characteristics of tattoos and PMU as part of the LIFE-Adult-study, a population-based cohort study. The control group without tattoos was from the same cohort and adjusted for confounders based on age, sex, smoking-status, body mass index, alcohol consumption and socioeconomic status. Of 4,248 participants, 7.4% (n=320) had either a tattoo (4.7%; n=199) or a permanent make-up (3.1%; n=135), or both (n=14). Thereof 5% (16/320) reported medical complications in relation to their tattoos or PMUs. Regarding systemic chronic health effects, increased odds ratios among the tattooed population were found for cardiologic diseases and liver toxicity. For non-melanoma skin cancer, results from the tattoo questionnaire gave no indication for any tumour development at the site of the tattoo. Our results demonstrate an increased risk for cardiologic and liver effects in participants bearing a tattoo. Strong differences in the observed effects between men and women point on the presence of a sex-specific bias. Even if no statistically robust conclusion can be drawn due to the small sample size, the results suggest that cardiologic outcomes and liver toxicity in tattooed individuals should be investigated further using prospective designs in larger cohorts.
Conspecific brood parasitism in the barn swallow (Hirundo rustica)
Authors: Jelínek Václav , Mari Lisandrina , Petrželková Adéla , Albrechtová Jana , Cepák Jaroslav , Kuhn Sylvia , Munclinger Pavel , Tomášek Oldřich , Šulc Michal , Albrecht Tomáš
Published: February 2025

Conspecific brood parasitism (CBP) has been reported in many altricial avian species, yet its prevalence and underlying behavioural mechanisms remain poorly understood. We studied CBP in the barn swallow (Hirundo rustica), a species in which conspecific brood parasitism has been reported. We conducted parentage analysis on 1945 barn swallow broods involving 7816 offspring. Samples were collected over 12 breeding seasons at 5 colonies. Contrary to expectations, we identified only six cases of CBP (0.3 % of broods). By identifying all individuals involved, i.e. the parasitic females, the female hosts and the males that fathered the parasitic eggs, we determined that four cases of CBP resulted from either a failed nest takeover, the disappearance of a female partner or a disruption caused by researchers. Based on a review of the literature on CBP in seven other Hirundinidae, we conclude that there is only reliable evidence for CBP in cliff swallows (Petrochelidon pyrrhonata). Studies on other species either failed to identify the parasitic females or do not present sufficient evidence supporting the occurrence of CBP. Several studies relied on the appearance in the nest of two eggs within 24 hours to conclude that CBP occurred. However, based on the parentage analysis, we show that CBP only occurred in one out of 11 such cases in barn swallows. Our findings highlight that CBP is rare in our barn swallow populations, and have been likely overestimated in other studies. We emphasize the importance of frequent nest checks and rigorous genetic validation in CBP research. Overall, our results challenge existing assumptions about the prevalence of CBP and provide insights into the behavioural mechanisms that lead to CBP, with ecological and evolutionary implications.
Chromato-kinetic fingerprinting enables multiomic digital counting of single disease biomarker molecules
Authors: Banerjee Pavel , Ray Sujay , Dai Liuhan , Sandford Erin , Chatterjee Tanmay , Mandal Shankar , Siddiqui Javed , Tewari Muneesh , Walter Nils G.
Published: February 2025

Early and personalized intervention in complex diseases requires robust molecular diagnostics, yet the simultaneous detection of diverse biomarkers—microRNAs (miRNAs), mutant DNAs, and proteins—remains challenging due to low abundance and preprocessing incompatibilities. We present Biomarker Single-molecule Chromato-kinetic multi-Omics Profiling and Enumeration (Bio-SCOPE), a next-generation, triple-modality, multiplexed detection platform that integrates both chromatic and kinetic fingerprinting for molecular profiling through digital encoding. Bio-SCOPE achieves femtomolar sensitivity, single-base mismatch specificity, and minimal matrix interference, enabling precise, parallel quantification of up to six biomarkers in a single sample with single-molecule resolution. We demonstrate its versatility in accurately detecting low-abundance miRNA signatures from human tissues, identifying upregulated miRNAs in the plasma of prostate cancer patients, and measuring elevated interleukin-6 (IL-6) and hsa-miR-21 levels in cytokine release syndrome patients. By seamlessly integrating multiomic biomarker panels on a unified, high-precision platform, Bio-SCOPE provides a transformative tool for molecular diagnostics and precision medicine.
Genetics of cardiometabolic disease progression
Authors: Rivas Manuel A , Justesen Johanne Marie , Venkataraman Guhan , Tibshirani Robert , Li Ruilin , Hastie Trevor , Knowles Joshua
Published: February 2025

Background: Genome-wide association studies have been crucial in gaining insights into the genetics of cardiometabolic diseases. However, little is known about the genetics of cardiometabolic disease progression which may have both a different genetic architecture and significant implications for treatment decisions. Disease progression can be ascertained by the time from the first disease diagnosis to a second qualifying event (e.g. diagnostic lab, code or procedure). While data of this nature have been available in large repositories such as the UK Biobank, large-scale genome-wide screens in a time-to-event setting have been extremely challenging due to various computational and statistical challenges. Methods and Results: We applied our method, snpnet-Cox, that has proven to be an effective method for simultaneous variable selection and estimation in high-dimensional settings, to examine the genetic contributions to cardiometabolic disease progression, measured by time from disease diagnosis to time of complication/comorbidity diagnosed or procedure in the UK Biobank. We apply a Cox regression model in a time-to-event setting to compute polygenic hazard scores (PHS). We identified ten new PHS that significantly predict disease progression. One example is the PHS that significantly predicts the time from hyperlipidemia diagnosis to having coronary artery bypass graft (CABG) surgery performed (Hazards Ratio 1.3 per PHS standard deviation: p=4.5x10-9). In this PHS, we identified a common variant, rs11041816 (downstream of LMO1), which protects against this disease progression (beta = -0.05). Conclusion: snpnet-Cox is a fast and reliable tool to compute PHS capturing genetics in the time-to-event setting. The computed PHS can be used to stratify individuals with an underlying diagnosis (e.g. hyperlipidemia) into different trajectories disease progression (e.g CABG) thereby identifying potential points of intervention. With more time-to-event data to be released, this approach can provide great insight into disease progression at the fraction of computational cost necessary. We make available ten polygenic hazard scores that we find to be significant predictors of cardiometabolic disease progression. Key words: Genetics, cardiometabolic diseases, polygenic hazards score, Lasso, prediction, hyperlipidemia, operation
Species-specific detection ofSchistosoma japonicumusing the ‘SNAILS’ DNA-based biosensor
Authors: Webb Alexander J. , Zhao Qin-Ping , Allan Fiona , Kelwick Richard J. R. , Emery Aidan M. , Freemont Paul S.
Published: February 2025

The neglected tropical disease schistosomiasis continues to be a global health concern, especially in low- and middle-income countries, with at least 250 million people infected worldwide and a further 779 million at risk of infection.Schistosoma japonicum, which is found in parts of South Asia, causes intestinal schistosomiasis in humans, as well as infecting up to forty other mammalian species. Therefore, novel diagnostics that can detectS. japonicumare desirable. In this study, we have further developed and refined the ‘SNAILS’ DNA-based biosensor technology for the detection of schistosomes and have applied this to the specific detection ofS. japonicum. Several new ‘SNAILS’ probe pairs were developed, and our optimised design successfully detected and differentiated between genomic DNA isolated from laboratory-derivedSchistosoma mansonicercariae andS. japonicumcercariae isolated from sites in the People’s Republic of China.
A Litmus Test for Confounding in Polygenic Scores
Authors: Smith Samuel Pattillo , Smith Olivia S. , Mostafavi Hakhamanesh , Peng Dandan , Berg Jeremy J. , Edge Michael D. , Harpak Arbel
Published: February 2025

Polygenic scores (PGSs) are being rapidly adopted for trait prediction in the clinic and beyond. PGSs are often thought of as capturing the direct genetic effect of one’s genotype on their phenotype. However, because PGSs are constructed from population-level associations, they are influenced by factors other than direct genetic effects, including stratification, assortative mating, and dynastic effects (“SAD effects”). Our interpretation and application of PGSs may hinge on the relative impact of SAD effects, since they may often be environmentally or culturally mediated. We developed a method that estimates the proportion of variance in a PGS (in a given sample) that is driven by direct effects, SAD effects, and their covariance. We leverage a comparison of a PGS of interest based on a standard GWAS with a PGS based on a sibling GWAS—which is largely immune to SAD effects—to quantify the relative contribution of each type of effect to variance in the PGS of interest. Our method, Partitioning Genetic Scores Using Siblings (PGSUS, pron. “Pegasus”), breaks down variance components further by axes of genetic ancestry, allowing for a nuanced interpretation of SAD effects. In particular, PGSUS can detect stratification along major axes of ancestry as well as SAD variance that is “isotropic” with respect to axes of ancestry. Applying PGSUS, we found evidence of stratification in PGSs constructed using large meta-analyses of height and educational attainment as well as in a range of PGSs constructed using the UK Biobank. In some instances, a given PGS appears to be stratified along a major axis of ancestry in one prediction sample but not in another (for example, in comparisons of prediction in samples from different countries, or in ancient DNA vs. contemporary samples). Finally, we show that different approaches for adjustment for population structure in GWASs have distinct advantages with respect to mitigation of ancestry-axis-specific and isotropic SAD variance in PGS. Our study illustrates how family-based designs can be combined with standard population-based designs to guide the interpretation and application of genomic predictors.
Trends in gestational age at birth in the city of São Paulo, Brazil between 2012 and 2019
Authors: Lira Margarida Maria Tenório de Azevedo , de Freitas Marina , Bonilha Eliana de Aquino , Aly Célia Maria Castex , dos Santos Patrícia Carla , Niy Denise Yoshie , Diniz Carmen Simone Grilo
Published: February 2025

Studies have shown that excessive obstetric interventions such as induced labor and caesarean sections have contributed to the shortening of the length of gestation, leading to a left shift in gestational age (GA) at birth. The aim of this study was to analyze trends in GA and the contribution of associated factors to changes in São Paulo city, Brazil during the period 2012-2019. We conducted an ecological time-series study of births in São Paulo using data from Brazil’s national live births information system (SINASC). We calculated the average annual percent change in the proportion of births by GA between 2012 and 2019 and between the first and second four-year periods of the time series by applying log transformation to the percentages, followed by Prais-Winsten regression. A total of 1,525,759 live births were analyzed. From 2015, there was an increase in the proportion of live births between 39 and 40 weeks from 2015 and a fall in the proportion of early term (37-38 weeks) and preterm (< 37 weeks) births throughout the study period. The average annual increase in the proportion of births at 39 and 40 weeks was 7.9% and 5.7%, respectively, while the proportion of births at other gestational ages showed a statistically significant reduction over the study period. These reductions were more pronounced in the first four-year period (2012-2015). The same trend was observed when the data were analyzed by type of delivery, type of service (public or private), maternal age, and maternal education level. The findings show that there was a right shift in the GA curve during the study period and a reduction in the proportion of preterm and early term births. These changes were more pronounced in births that occurred in private hospitals. These changes reflect public policies implemented to reduce obstetric interventions such as induced labor and caesarean section before labor, especially before 39 weeks of gestation.
A Quantitative Approach to Mapping Mitochondrial Specialization and Plasticity
Authors: Monzel Anna S. , Devine Jack , Kapri Darshana , Enriquez Jose Antonio , Trumpff Caroline , Picard Martin
Published: February 2025

Mitochondria are a diverse family of organelles that specialize to accomplish complimentary functions1–3. All mitochondria share general features, but not all mitochondria are created equal4.Here we develop a quantitative pipeline to define the degree of molecular specialization among different mitochondrial phenotypes – ormitotypes. By distilling hundreds of validated mitochondrial genes/proteins into 149 biologically interpretable MitoPathway scores (MitoCarta 3.05) the simple mitotyping pipeline allows investigators to quantify and interpret mitochondrial diversity and plasticity from transcriptomics or proteomics data across a variety of natural and experimental contexts. We show that mouse and human multi-organ mitotypes segregate along two main axes of mitochondrial specialization, contrasting anabolic (liver) and catabolic (brain) tissues. In cultured primary human fibroblasts exhibiting robust time-dependent and treatment-induced metabolic plasticity6–8, we demonstrate how the mitotype of a given cell type recalibrates i) over time in parallel with hallmarks of aging, and ii) in response to genetic, pharmacological, and metabolic perturbations. Investigators can now useMitotypeExplorer.organd the associated code to visualize, quantify and interpret the multivariate space of mitochondrial biology.
Extracellular vesicle production and membrane uptake promote repair and antibiotic tolerance inE. coli
Authors: Bos Julia , Abou Haydar Yasmina , Mayboroda Olena , Commere Pierre Henri , Mazel Didier
Published: February 2025

Bacterial extracellular vesicles (EVs) are nanosized lipid structures released in response to environmental stressors, such as phages and antibiotics. Despite their critical role in bacterial adaptability, the mechanisms by which EVs interact with membranes under stress remain poorly understood, due to challenges in visualizing these dynamic processes in live bacteria. Here, we use high-resolution fluorescence microscopy, flow cytometry, and cryo-electron microscopy to investigate EV production and uptake inEscherichia coliexposed to sub-minimum inhibitory concentration doses of polymyxin B (Pmb), a membrane-active antimicrobial peptide. Using fluorescently labeled Pmb and EVs, we track Pmb insertion and removal from membranes, EV production and uptake, and their effects on cell growth. Our findings demonstrate that EV production rapidly sequesters Pmb in the medium and facilitates its removal from bacterial membranes. For the first time, we demonstrated that EVs act as membrane plugs by adhering to or fusing with Pmb-damaged membranes. These dynamic processes work together to reduce the antibiotic load from the membranes, turn off the RcsA-mediated membrane stress response, and enable cells to resume growth. Although EVs do not provide resistance to Pmb, they enhance the survival and tolerance of bacterial populations. This study uncovers the dual role of EVs in Pmb sequestration and membrane repair, providing new insights into antibiotic tolerance mechanisms and paving the way for innovative approaches to combat antimicrobial resistance.
An unclean slate, discrepancies between food input and recovered protein signal from experimental foodcrusts
Authors: Dekker Joannes Adrianus Antonius , Hagan Richard , Collins Matthew , Hendy Jessica
Published: February 2025

Organic residues are a rich source of biomolecular information on ancient diets. In particular, foodcrusts, charred residues on ceramics, are commonly analysed for their lipid content and to a lesser extent protein in order to identify foods, culinary practices and material culture use in past populations. However, the composition of foodcrusts and the factors behind their formation are not well understood. Here we analyse proteomic data (available via ProteomeXchange with identifier PXD059930) from foodcrusts made using a series of mixtures of protein- (salmon flesh), lipid- (beef fat) and carbohydrate-rich (beetroot) foods to investigate the relationship between the biomolecular composition of the input and the recovered signal using conventional methods applied to archaeological material. Additionally, using 3D modelling we quantify the volume of foodcrust generated by different ingredient combinations The results highlight biases in the data obtained in the analyses of organic residues both in terms of identified resources reflecting the cooked foodstuffs, e.g. an overrepresentation of fish proteins, as well as with regards to the abundance of foodcrust, for example mixtures of only salmon and beef fat resulted in relatively small amounts of foodcrust, and suggest caution in interpreting the composition of residues formed from complex mixtures of foodstuffs.
Sequencing of a dairy isolate unlocksKluyveromyces marxianusas a host for lactose valorization
Authors: Thornbury Mackenzie , Knoops Adrien , Summerby-Murray Iain , Dhaliwal James , Johnson Sydney , Utomo Joseph Christian , Joshi Jaya , Narcross Lauren , Remondetto Gabriel , Pouliot Michel , Whiteway Malcolm , Martin Vincent J.J.
Published: February 2025

The use of genetically modified non-conventional yeast provides significant potential for the bioeconomy by diversifying the tools available for the development of sustainable and novel products. In this study, we sequenced and annotated the genome ofKluyveromyces marxianusY-1190 to establish it as a platform for lactose valorization. The strain was chosen for rapid growth on lactose-rich dairy permeate, high transformation efficiency, and ease of culturing in bioreactors. Genomic sequencing revealed thatK. marxianusY-1190 possesses single nucleotide polymorphisms associated with efficient lactose metabolism. The strain is diploid with notable genomic heterogeneity, which appears to be critical for its robust growth and acid tolerance. To further exploit this platform strain, we developed protocols for gene and chromosome manipulation using CRISPR editing, constructed and validated a series of promoters compatible with MoClo vectors, and designed synthetically inducible promoters forK. marxianus. These tools enable precise control over gene expression, allowing for the tailored optimization of metabolic pathways and production processes. The synthetic promoters provide flexibility for dynamic expression tuning, while the CRISPR-based editing protocols facilitate targeted genetic modifications with high efficiency. Together, these advancements significantly enhance the genetic toolbox forK. marxianus, positioning it as a versatile platform for industrial biotechnology. These tools open new opportunities for the sustainable production of bio-based chemicals, fuels, and high-value products, leveraging lactose-rich feedstocks to contribute to a circular economy.
Repurposing of the RIPK1 selective benzo[1,4]oxazepin-4-one scaffold for the development of a type-III LIMK1/2 inhibitor
Authors: Mandel Sebastian , Hanke Thomas , Mathea Sebastian , Chatterjee Deep , Saraswati Hayuningbudi , Berger Benedict-Tilman , Schwalm Martin-Peter , Yamamoto Satoshi , Tawada Michiko , Takagi Terufumi , Röhm Sandra , Corrionero Ana , Alfonso Patricia , Baena Maria , Elson Lewis , Menge Amelie , Krämer Andreas , Pereira Raquel , Müller Susanne , Krause Daniela S. , Knapp Stefan
Published: February 2025

Benzoxazepinones have been extensively studied as exclusively selective RIP kinase 1 inhibitors. This scaffold binds as a type-III inhibitor targeting the αC-out/DFG-out conformation. This inactive conformation results in a large expansion of the kinase back pocket, a conformation that has also been reported for LIM kinases. Scaffold hopping is common in the design of orthosteric kinase inhibitors, but has not been explored in the design of allosteric inhibitors, mainly due to the typically exclusive selectivity of type III inhibitors. Here, we hypothesized that the shared structural properties of LIMKs and RIPKs could lead to novel type III LIMK inhibitors using the benzoxazepinone scaffold. We report the discovery of a novel LIMK1/2 inhibitor that relies on this scaffold-based approach. The discovered compound10showed low nanomolar potency on LIMK1/2 and exceptional selectivity, as confirmed by a comprehensive selectivity panel with residual RIPK activity as the only off-target. The study provides one of the few examples for scaffold hopping for type-III inhibitors which are usually associated with exclusive target selectivity.

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Active zone maturation state controls synaptic output and release mode and is differentially regulated by neuronal activity
Authors: Akbergenova Yulia , Matthias Jessica , Littleton J. Troy
Published: February 2025

Synapse formation requires the gradual accumulation of cytomatrix proteins and voltage-gated Ca2+channels (VDCCs) at presynaptic active zones (AZs) to support neurotransmitter release. To correlate AZ maturation with synaptic output, quantal imaging was performed at serially imaged time-stampedDrosophilasynapses. Evoked release strength correlated strongly with AZ age and accumulation of late AZ scaffolds, while immature sites lacking VDCC accumulation supported spontaneous release. To examine how neuronal activity regulates AZ maturation and protein accumulation, the effects of disruptions to SV fusion or action potential generation were analyzed. Decreasing neuronal activity reduced AZ seeding and caused hyperaccumulation of presynaptic material at existing AZs. Although enlarged AZs are also observed inrab3mutants, activity reduction acted through an independent mechanism that required postsynaptic glutamate receptor-dependent signaling. Together, these data indicate AZ maturation state sets distinct presynaptic release modes and output strength, with neuronal activity shaping both AZ number and size across development.
Mental exploration of future choices during immobility theta oscillations
Authors: Wang Mengni , Yuan Li , Leutgeb Stefan , Leutgeb Jill K.
Published: February 2025

Mental exploration enables flexible evaluation of potential future choices, guiding decision-making without requiring direct real-world iterations. Although the hippocampus is known to be active while imagining the future, the precise mechanisms that support mental exploration of future choices remain unclear. In the hippocampus, the theta rhythm (4-12 Hz) is prevalent during movement and supports memory coding during real-world exploration by organizing neuronal activity patterns into short virtual path segments (theta sequences) around the rat’s location. We observed these theta-related neural activity patterns during movement in a hippocampus-dependent working memory task and also, unexpectedly, theta oscillations and theta-related neural activity during immobility. Compared to standard theta sequences during movement, theta sequences during immobility differed in that they occurred at a shifted theta phase and preferentially represented remote locations, in particular the next choice in the working memory task. Coding for future locations was also observed during awake sharp wave ripple, but these short-lasting events occurred rarely and were biased toward frequently visited locations. Therefore, our findings suggest that recurring bouts of theta oscillations during immobility, which are also observed in primates and humans, support the cognitive demands of mental exploration in the hippocampal network and facilitate ongoing predictions of future choices.
Time-course Transcriptomic Dataset of Gallic Acid-induced Human Cervical Carcinoma HeLa Cell Death
Authors: Tang Ho Man , Cheung Peter Chi Keung
Published: February 2025

Gallic acid is a natural phenolic acid that displays potent anti-cancer activity in clinically relevant cell culture and rodent models. Although research has focused on determining the efficacy of gallic acid against various types of human cancer cells, the molecular mechanisms governing the anti-cancer properties of gallic acid remains largely unclear, and a transcriptomic study of gallic acid-induced cancer cell death has rarely been re-ported. Therefore, we performed time-course bulk RNA-sequencing study to elucidate the molecular signature of gallic acid-induced cell death in human cervical cancer HeLa cells, as this is a widely used in vitro model in the field. Our RNA-sequencing dataset covers the early (2nd hour), middle (4th, 6th hour), and late (9th hour) stages of the cell death process after exposure of HeLa cells to gallic acid, and the untreated (0th hour) cells served as controls. Differential expression of messenger RNAs (mRNA) and long non-coding RNAs (lncRNA) were identified in each time point in the dataset. In summary, this dataset is a unique and valuable resource with which the scientific community can explore the molecular mechanisms and identify key regulators of the gallic acid-induced cancer cell death process.
A feedback amplifier circuit with Notch and E2A orchestrates T-cell fate and suppresses the innate lymphoid cell lineages during thymic ontogeny
Authors: Miyazaki Kazuko , Horie Kenta , Watanabe Hitomi , Hidaka Reiko , Hayashi Rinako , Hayatsu Norihito , Fujiwara Kentaro , Kuwata Rei , Uehata Takuya , Ochi Yotaro , Takenaka Makoto , Kawaguchi Risa Karakida , Ikuta Koichi , Takeuchi Osamu , Ogawa Seishi , Hozumi Katsuto , Holländer Georg A. , Kondoh Gen , Akiyama Taishin , Miyazaki Masaki
Published: February 2025

External signals from the thymic microenvironment and the activities of lineage-specific transcription factors (TFs) instruct T-cell versus innate lymphoid cell (ILC) fates. However, mechanistic insights into how factors such as Notch1–Delta-like-4 (Dll4) signaling and E-protein TFs collaborate to establish T-cell identity remain rudimentary. Using multiple in vivo approaches and single-cell multiome analysis, we identified a feedback amplifier circuit that specifies fetal and adult T-cell fates. In early T progenitors (ETPs) in the fetal thymus, Notch signaling minimally lowered E-protein antagonistId2levels, and highId2abundance favored the differentiation of ETPs into ILCs. Conversely, in the adult thymus, Notch signaling markedly decreasedId2abundance in ETPs, substantially elevating E-protein DNA binding and in turn promoting the activation of a T-cell lineage-specific gene expression program linked with V(D)J gene recombination and T-cell receptor signaling. Our findings indicate that, in the fetal versus the adult thymus, a simple feedback amplifier circuit dictated by Notch-mediated signals andId2abundance enforces T-cell identity and suppresses ILC development.
Holographic Schwinger effect in flavor-dependent systems
Authors: Lin Sheng , Liu Xuan , Chen Xun , Zhang Gen-Fa , Zhou Jing
Published: February 2025

The holographic Schwinger effect is investigated in systems with Nf=0, Nf=2, and Nf=2+1 using the Einstein-Maxwell-dilaton (EMD) model, incorporating equation of state and baryon number susceptibility information from lattice quantum chromodynamics (QCD). It is found that the critical electric field is smallest for Nf=0, indicating that the Schwinger effect is more likely to occur than in systems with Nf=2 and Nf=2+1. The critical electric field decreases with increasing chemical potential and temperature across all systems. Additionally, potential analysis confirms that the maximum total potential energy increases with the number of flavors, suggesting that existing particles may reduce the probability of particle pair production.

Published by the American Physical Society
2025
Supramolecular assembly of mebendazolium and dihydrogen phosphate ions in a new anthelmintic salt
Authors: Gutiérrez Eduardo L. , Russo Marcos G. , Narda Griselda E. , Brusau Elena V. , Ayala Alejandro P. , Ellena Javier
Published: February 2025

A new mebendazolium dihydrogen phosphate phosphoric acid solid material was obtained and characterized by single-crystal X-ray diffraction and complementary solid-state techniques {systematic name: 5-benzoyl-2-[(methoxycarbonyl)amino]-1H-1,3-benzodiazol-3-ium dihydrogen phosphate–phosphoric acid (1/1), C16H14N3O3
+·H2PO4
−·H3PO4}. Structure solution confirmed proton transfer from phosphoric acid towards the basic imidazole ring of mebendazole. The mebendazolium cation and the dihydrogen phosphate anion assemble in the solid state in a cyclic hydrogen-bond-driven supramolecular motif, as observed in all mebendazolium/oxyanions structures reported in the literature. This salt crystallizes in the monoclinic P21/c (No. 14) space group. A detailed study of the crystal structure performed by atom-to-atom and global Hirshfeld surface analysis indicates that several hydrogen bonds act as the main intermolecular interactions stabillizing the material. The new material is stable up to 458 K.
Fostering sustainable consumption: the interplay of pro-social behavior and social norms in reducing food waste in India
Authors: Chakraborty Debarun
Published: February 2025

Purpose

Food waste constitutes a critical global dilemma, presenting substantial environmental, economic and social challenges, with around one-third of all food intended for human use being discarded annually. This waste depletes essential resources, increases greenhouse gas emissions and intensifies food poverty. Comprehending the factors contributing to food waste is crucial for formulating effective methods to alleviate this issue.

Design/methodology/approach

The responses have been collected from Indian households using longitudinal techniques. In Study 1, 481 respondents responded to the questions, and in Study 2, finally, 453 respondents responded.

Findings

This study examines the relationship between attitudes about food waste, intents to mitigate waste and several influencing factors like price sensitivity, altruistic behavior, awareness of food waste and societal norms.

Originality/value

The study seeks to elucidate consumer behavior by analyzing these relationships and identify practical interventions that can encourage a more sustainable food consumption approach, thereby aiding in the reduction of food waste and the promotion of responsible consumption practices.
Innovating bio-lubricant design: utilizing Mordred descriptors for model development and thermal stability prediction of novel compounds
Authors: Ma’ruf Muhammad , Fukuda Kanao , Liza Shahira , Fajar Rizqon
Published: February 2025

Purpose

Developing bio-lubricants for high-temperature applications, such as engine operations, requires reliable thermal stability assessment. This study aims to create a predictive tool to evaluate thermal stability using existing organic compounds data. The model predicts the onset temperature (T onset) of bio-lubricant candidates derived from epoxidation with various amine nucleophiles, enhancing initial selection efficiency and reducing reliance on traditional trial-and-error methods.

Design/methodology/approach

Using the Python library Mordred, molecular descriptors were calculated from the SMILES structures of 126 compounds with known T onsets. These descriptors were inputs for machine learning models predicting the thermal stability of bio-lubricants. The models were evaluated on training and test data sets and validated with novel synthesized compounds.

Findings

The predictive model showed strong performance on the test data set, with an R² of 0.93 and a root mean square error of 17.77. In external validation, the model estimated the thermal stability of a novel bio-lubricant compound (MA-EPO) at 290.7°C, closely matching the actual T onset of approximately 300°C.

Originality/value

This research introduces a method for predicting the thermal stability of bio-lubricants using machine learning and open-source libraries. This approach significantly advances the field by improving the efficiency of bio-lubricant development for high-temperature applications. It provides a cost-effective and time-saving alternative to traditional experimental methods, serving as a valuable resource for researchers and developers in the bio-lubricant industry.