bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoding Labour Epidural Analgesia and Autism: Navigating the Abyss Between Statistical Significance, Biological Plausibility, and Clinical Relevance
Authors: Devroe S , Bleeser T , Lucas N
Published: February 2025

(Eur J Anaesthesiol. 2024;41(4):257–259. doi:10.1097/EJA.0000000000001965)

Widespread use of labor epidural analgesia (LEA) in developed countries as the leading pain management technique during pregnancy without many adverse perinatal events should suggest its efficacy and safety. However, various researchers and some in the general public have begun to question the lasting effects in children born in the setting of maternal LEA use. One such neurodevelopmental disorder being examined is autism spectrum disorder (ASD). A 2020 study claimed a 37% risk increase for ASD diagnoses in children whose mother used LEA during the birthing process. Although this and other similar publications have received widespread attention, in this editorial, authors caution mothers and providers to carefully consider the complexity of the neurodevelopmental disorder etiology.
Ropivacaine Perineal Infiltration for Postpartum Pain Management in Episiotomy Repair: A Double-Blind, Randomized, Placebo-Controlled Trial
Authors: Cardaillac C , Planche L , Dorion A , Ploteau S , Thubert T , Lefizelier E , Winer N , Ducarme G
Published: February 2025

(BJOG. 2024;131(7):899–907. doi:10.1111/1471-0528.17266)

Episiotomy, a surgical technique that widens the vaginal opening to facilitate delivery, continues to be frequently performed despite global suggestions to reduce its frequency, with prevalence varying from 8% to 59%. Postpartum perineal pain affects a large majority of women, with 97% experiencing it in the first 24 hours and 61% to 76% experiencing it from days 7 to 10. This discomfort may last for months and is associated with postpartum depression and sexual dysfunction, affecting 50% of women a year after having an episiotomy or a third-degree tear.
“Detect Anemia Preoperatively”: A Scoping Review of Recommendations
Authors: Schneider Katja , Sauer Diana , Wolf Lorenz , Willms Arnulf G.
Published: February 2025

Background:

Preoperative anemia significantly impacts patient outcomes, prompting increasing global implementation of patient blood management (PBM) measures. Timely diagnosis and differentiation of preoperative anemia are crucial components of PBM to maximize its effectiveness. Despite this, comprehensive implementation remains inconsistent. This scoping review aims to give an overview of recommendations regarding preoperative anemia management to detect gaps in knowledge and emerging ideas.

Methods:

A scoping review, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, investigated preoperative anemia detection, focusing on patient population, timing, extent, and process of investigations. PubMed and ScienceDirect were searched for English and German articles published in the last 5 years, supplemented by manual selection. Pediatric and obstetric recommendations were excluded. Results were synthesized based on key questions.

Results:

Four hundred sixty-five articles were screened, and 80 met the inclusion criteria, including 25 clinical practice guidelines. Most (n = 62) suggested “detect and correct” anemia without further specification. The rest advised conducting investigations early, ideally up to 30 days before major procedures with expected blood loss >500 mL. Recommended tests include blood counts, various iron parameters, folic acid/vitamin B12, inflammation markers, and renal, hepatic, and thyroid function tests. Ten articles described detailed algorithms. Other key recommendations included using reticulocyte hemoglobin, point-of-care Hb measurements, and automated laboratory algorithms. The underlying quality of scientific evidence is heterogeneous.

Conclusions:

International recommendations on the detection of preoperative anemia are heterogeneous and often generic. Automated algorithms could make a significant contribution to practicability. While practice-oriented guidelines, especially by surgical societies, could promote standardized and efficient implementation, further research is needed to improve the quality of underlying scientific evidence.
Global and regional burden of kidney cancer due to high body index in adults from 1990 to 2021 and predictions to 2036
Authors: Zhang Meng , Shen Yuefan , Gao Jianguo , Shao Sihai
Published: February 2025

Monitoring the evolving global and regional burden of kidney cancer attributable to high BMI is vital for informing prevention and healthcare policies. This study aimed to evaluate historical trends in the global and regional burden of kidney cancer attributable to high BMI from 1990 to 2021 and to predict future trends through 2036 for individuals aged 20 years and older. We conducted a retrospective analysis using the Global Burden of Disease 2021 database. We analyzed data on mortality and disability-adjusted life years (DALYs) linked to kidney cancer from high BMI. Stratifications included sociodemographic index (SDI), region, sex, and age. Temporal trends were assessed using joinpoint regression models, while the relationship between SDI and regional burden was examined. Projections were generated using Bayesian age-period-cohort models. In 2021, high BMI contributed to 19.86% of global kidney cancer deaths (0.032 million) and 19.00% of DALYs (0.782 million), representing an increase since 1990. Globally, age-standardized mortality rate and age-standardized disability rate have declined in recent years. However, rates have risen in developing regions such as South Asia and East Asia. Projections indicate stable global rates with slight fluctuations through 2036. The global kidney cancer burden attributable to high BMI shows signs of decline but continues to rise in some developing regions. Addressing this disparity requires strengthening obesity prevention and control strategies tailored to regional needs.
Observations of Communication Practices Between Men Who Have Sex With Men With HIV and HIV Specialist Nurses During Routine Consultations Regarding Sexual Health Counseling in the Netherlands: A Qualitative Study
Authors: de Munnik Suzanne , den Daas Chantal , Ammerlaan Heidi Sophia Maria , Kok Gerjo , de Wit John , Vervoort Sigrid Cornelia Johanna Maria
Published: February 2025

This study investigated how HIV specialist nurses communicate with men who have sex with men with HIV during routine consultations with a focus on sexual health counseling in the Netherlands. In this multicenter observational study, 16 video-recorded consultations from four HIV treatment centers were analyzed. Verbatim transcriptions were analyzed to assess the topics discussed, the duration of consultations, time spent on sexual health counseling, and specific issues covered. Communication skills were evaluated through a predefined framework. The findings indicated inconsistent coverage of sexual health, varied topics, and a lack of structure. Various communication skills and techniques were applied inconsistently. Given these findings, we recommend implementing communication strategies during routine consultations to improve the quality of sexual health counseling, especially for men who have sex with men with HIV. This is essential to improve the quality of sexual health counseling for persons with HIV, especially men who have sex with men.
Respiratory dysfunction in patients that recovered from coronavirus disease 2019 pneumonia: A six-month follow-up study
Authors: Meng Xianglin , Luo Peiyao , Wang Jianpeng , Wu Haolan , Sun Chongyang , Kang Kai , Yu Kaijiang , Zhao Mingyan
Published: February 2025

Background:

This study investigates the clinical features and pulmonary functions of coronavirus disease 2019 (COVID-19) pneumonia survivors at 3 or 6 months after diagnosis in the Heilongjiang Province, China.

Methods:

Forty-six patients with COVID-19 pneumonia diagnosed starting from February 2020 were enrolled in this study for follow-up in August 2020. These patients were categorized into three groups: Group A (n = 24) and Group B (n = 11), who were diagnosed with moderate or severe pneumonia and followed up at three months after diagnosis, and Group C (n = 11), who were diagnosed with severe pneumonia and were followed up at 6 months after diagnosis. Pulmonary functions, arterial blood gas analysis, and clinical features, including chest high-resolution computed tomography (HRCT), blood tests, and health-related quality of life during hospitalization and at follow-up visits, were collected and analyzed.

Results:

Abnormal PO2 (A-a) was more prevalent in severe cases (Groups B and C) than in moderate cases (Group A). Respiratory dysfunction was common in our patients. HRCT showed that the abnormal computed tomography (CT) scores of severe cases (Groups B and C) were significantly higher than those of moderate cases (Group A). During the follow-up period, lung abnormalities gradually resolved in the first three months (Groups A and B); however, further resolution was not significant from 3-6 months (Groups B and C).

Conclusion:

Although pulmonary interstitial changes due to COVID-19 pneumonia gradually reverse over time, respiratory dysfunction is common and appears to persist for at least up to 6 months in patients who have recovered from COVID-19 pneumonia.
Qualifying Cochlear Implant Candidates—Does it Matter How Patients Are Qualified?
Authors: Lee David S. , Herzog Jacques A. , Walia Amit , Smetak Miriam R. , Pavelchek Cole , Durakovic Nedim , Wick Cameron C. , Ortmann Amanda J. , Buchman Craig A. , Shew Matthew A.
Published: February 2025

Objective

Evaluate variable qualification criteria for cochlear implant (CI) recipients and 12-month speech perception outcomes.

Study Design

Retrospective cohort study.

Setting

HERMES national database and nonoverlapping single-institution CI database.

Patients

A total of 2,124 adult unilateral CI recipients categorized by qualifying status: AzBio in quiet (n = 1,239), +10 dB SNR (but not in quiet; n = 519), +5 dB SNR (but not in quiet or +10 dB SNR; n = 366); CNC ≤40% (n = 1,037), CNC 41% to 50% (n = 31), and CNC 51% to 60% (n = 20).

Interventions

CI.

Main Outcome Measures

Pre- and 12-month postoperative speech perception performance. Clinically significant improvement was defined as ≥15% gain.

Results

Quiet qualifiers experienced improvement in all listening conditions, whereas +10 dB SNR and +5 dB SNR qualifiers only improved in their qualifying condition and implanted ear CNC. When stratified by expanded Medicare criteria (binaural AzBio ≤60% correct), patients that qualified in quiet experienced improvements regardless of qualifying threshold or background noise. However, those that qualified in noise and AzBio ≤60% experienced mixed results in quiet and limited gain in background noise. When ≤60% criteria was applied to CNC of the worse ear, ≤40% qualifiers experienced large improvements in all tested conditions, but those who qualified by 41% to 50% or 51% to 60% only demonstrated modest improvements in AzBio sentence testing.

Conclusions

Quiet qualifiers improved in all testing conditions, while those qualifying in noise improved in their qualifying condition. Patients who qualified by expanded Medicare criteria (≤60%) showed improvement when qualifying with AzBio in quiet, but should be used with caution when qualifying patients in background noise or CNC due to more limited gains in performance.
Characterization of the Expression and Role of Striatin-Interacting Protein 2 in Mouse Cochlea
Authors: Li Siyu , Qiu Yue , Li Ao , Lu Jie , Ji Xinya , Hao Wenli , Cheng Cheng , Gao Xia
Published: February 2025

Hypothesis

In this study, we aimed to examine the cochlear expression pattern and function of Striatin-interacting protein 2 (STRIP2) by using animal models.

Background

Sensorineural hearing loss often results from genetic defects in hair cell (HC) development and function. STRIP2 is a part of the striatin-interacting phosphatase and kinase (STRIPAK) complex, which plays important regulatory roles in cell fate determination, proliferation, cytoskeletal organization, and cell morphology. A recent study revealed Strip2 as the candidate gene that regulates positive selection in HC lineages. However, its role in the inner ear has not been identified.

Methods

Strip2 knockout mouse model was used to examine the cochlear expression pattern and function of STRIP2. Auditory brainstem response test was used to evaluate the hearing function of mice. Immunostaining and scanning electron microscope were used to study hair cells, synapses, and stereocilia of cochlea.

Results

Immunostaining showed that cytoplasmic STRIP2 expression in hair cells increased from postnatal day (P) 3 to P14. Despite having normal hearing thresholds, hair cell numbers, and stereocilia morphology until P90, the deletion of Strip2 resulted in a mild reduction in ribbon synapse density, suggesting a late onset of cochlear synaptic defects.

Conclusion

Our results revealed that STRIP2 was abundantly expressed in hair cells; however, the hearing function of Strip2
−/− mice was comparable to that of control mice until P90, and a mild decrease in ribbon synapse number was detected at P60 and P90. Further studies on STRIP2 and its associated complexes will provide new insights into the pathways involved in inner ear development and function.
Incidence and Risk of Catheter-Related Thrombosis in Breast Cancer Patients With Implanted Ports
Authors: Luo Zebing , Xu Wanzhu , Guo Zhijun , Xu Manjia , Lv Xinxian , Chen Chujun
Published: February 2025

Objective

This study assessed the risk factors for thrombosis related to totally implantable venous access ports (TIVAPs) among breast cancer patients.

Methods

A single-center, retrospective, observational study was conducted. Demographic, disease-related, hematological, and TIVAP-related factors were assessed. Multiple logistic regression analysis was used to explore the influencing factors of TIVAP-related thrombosis.

Results

A total of 416 patients with breast cancer with TIVAPs were divided into 3 groups: no thrombosis (64.4%), asymptomatic thrombosis (32.3%), and symptomatic thrombosis (3.3%). Multiple logistic regression showed that with no thrombosis as the reference, the protective factors for asymptomatic thrombosis were chemotherapy and TIVAP placement in the left side of the chest wall. Risk factors were ≤1 comorbidity and the use of ceramics as the base material of the TIVAP reservoir. With no thrombosis as the reference, cancer clinical stage III and chemotherapy were identified as protective factors of symptomatic thrombosis.

Conclusion

Among breast cancer patients with a TIVAP, 32.3% had asymptomatic thrombosis and 3.3% had symptomatic thrombosis. Clinical staff should pay close attention to these indicators and identify high-risk patients with TIVAP-related thrombosis as early as possible.
Continuous Glucose Monitoring for Inpatients on Intravenous Insulin
Authors: Good Karen , Joshi Renu , Snell Vanessa
Published: February 2025

Purpose

This article describes a protocol used to implement a continuous glucose monitoring program for patients treated with intravenous insulin.

Description

Although continuous glucose monitoring is not indicated for use in hospitalized patients, the COVID-19 pandemic created an immediate need to effectively address the increasing number of people hospitalized with hyperglycemia. The article highlights the implementation process and key glycemic outcomes, discusses the impact of continuous glucose monitoring use on staff time and healthcare resource utilization, and provides information about program expansion.

Outcome

Most patients achieved established glycemic targets. Our program improved staff safety by reducing their exposure to infection. Use of continuous glucose monitoring decreased staff time by almost 2 hours per person per day compared with point-of-care testing and resulted in an average cost savings of $278.00 per patient.

Conclusion

Continuous glucose monitoring is safe and effective in managing glycemia among patients treated with intravenous insulin.
Multi-Metal Resistant Staphylococcus warneri strain TWSL_1: Revealing Heavy Metal Resistant Genomic Features by Whole Genome Sequencing
Authors: Dissanayake Dilani , Chandrasekharan2 Naduviladath , Wijayaratahna Dilrukshi
Published: February 2025

This study explores the genomic basis of heavy metal resistance in Staphylococcus warneri strain TWSL_1, isolated from industrial textile effluent. The strain exhibited strong resistance to Cd²⁺, Pb²⁺, and Cu²⁺, with minimum inhibitory concentrations of 50 mg/L, 1200 mg/L, and 75 mg/L, respectively. Whole-genome sequencing revealed a 2.66 Mb genome with 2,567 coding sequences and a 99.81% average nucleotide identity to S. warneri WS479. Comparative analysis identified key metal resistance genes, including cadmium efflux and cobalt-zinc-cadmium resistance proteins, absent in S. aureus RF122. Phylogenetic analysis confirmed its classification within S. warneri, with strong bootstrap support (100). Functional annotation highlighted metabolic versatility and stress response capabilities, supporting its adaptation to metal-rich environments. S. warneri TWSL_1 demonstrated high Pb²⁺ removal efficiency, reducing concentrations by over 70%, underscoring its bioremediation potential. These findings highlight S. warneri TWSL_1 as a promising candidate for heavy metal bioremediation, warranting further functional validation and application in environmental detoxification strategies.
Identification and classification of ion-channels across the tree of life: Insights into understudied CALHM channels
Authors: Taujale Rahil , Park Sung Jin , Gravel Nathan , Soleymani Saber , Carter Rayna , Boyd Kennady , Keuning Sarah , Ruan Zheng , Lü Wei , Kannan Natarajan
Published: February 2025

The ion channel (IC) genes encoded in the human genome play fundamental roles in cellular functions and disease and are one of the largest classes of druggable proteins. However, limited knowledge of the diverse molecular and cellular functions carried out by ICs presents a major bottleneck in developing selective chemical probes for modulating their functions in disease states. The wealth of sequence data available on ICs from diverse organisms provides a valuable source of untapped information for illuminating the unique modes of channel regulation and functional specialization. However, the extensive diversification of IC sequences and the lack of a unified resource present a challenge in effectively using existing data for IC research. Here, we perform integrative mining of available sequence, structure, and functional data on 419 human ICs across disparate sources, including extensive literature mining by leveraging advances in large language models to annotate and curate the full complement of the “channelome”. We employ a well-established orthology inference approach to identify and extend the IC orthologs across diverse organisms to above 48,000. We show that the depth of conservation and taxonomic representation of IC sequences can further be translated to functional similarities by clustering them into functionally relevant groups, which can be used for downstream functional prediction on understudied members. We demonstrate this by delineating co-conserved patterns characteristic of the understudied family of the Calcium Homeostasis Modulator (CALHM) family of ICs. Through mutational analysis of co-conserved residues altered in human diseases and electrophysiological studies, we show that evolutionary-constrained residues significantly alter gating functions. Thus, by providing new tools and resources for performing large comparative analyses on ICs, this study addresses the unique needs of the IC community and provides the groundwork for accelerating the functional characterization of dark channels for therapeutic intervention.
A pathogenic subpopulation of human glioma associated macrophages linked to glioma progression
Authors: Hei Yu Kenny Kwok , Abou-Mrad Zaki , Törkenczy Kristof , Schulze Isabell , Gantchev Jennifer , Baquer Gerard , Hopland Kelsey , Bander Evan D. , Tosi Umberto , Brennan Cameron , Moss Nelson S. , Hamard Pierre-Jacques , Koche Richard , Lareau Caleb , Agar Nathalie Y.R. , Merghoub Taha , Tabar Viviane
Published: February 2025

Malignant gliomas follow two distinct natural histories:de novohigh grade tumors such as glioblastoma, or lower grade tumors with a propensity to transform into high grade disease. Despite differences in tumor genotype, both entities converge on a common histologically aggressive phenotype, and the basis for this progression is unknown. Glioma associated macrophages (GAM) have been implicated in this process, however GAMs are ontologically and transcriptionally diverse, rendering isolation of pathogenic subpopulations challenging. Since macrophage contextual gene programs are orchestrated by transcription factors acting oncis-acting promoters and enhancers in gene regulatory networks (GRN), we hypothesized that functional populations of GAMs can be resolved through GRN inference. Here we show via parallel single cell RNA and ATAC sequencing that a subpopulation of human GAMs can be defined by a GRN centered around the Activator Protein-1 transcription factor FOSL2 preferentially enriched in high grade tumors. Using this GRN we nominate ANXA1 and HMOX1 as surrogate cell surface markers for activation, thus permitting prospective isolation and functional validation in human GAMs. These cells, termed malignancy associated GAMs (mGAMs) are pro-invasive, pro-angiogenic, pro-proliferative, possess intact antigen presentation but skew T-cells towards a CD4+FOXP3+ phenotype under hypoxia. Ontologically, mGAMs share somatic mitochondrial mutations with peripheral blood monocytes, and their presence correlates with high grade disease irrespective of underlying tumor mutation status. Furthermore, spatio-temporally mGAMs occupy distinct metabolic niches; mGAMs directly induce proliferation and mesenchymal transition of low grade glioma cells and accelerate tumor growth in vivo upon co-culture. Finally mGAMs are preferentially enriched in patients with newly transformed regions in human gliomas, supporting the view that mGAMs play a pivotal role in glioma progression and may represent a plausible therapeutic target in human high-grade glioma.
Therapeutic assessment of a novel mitochondrial complex I inhibitor inin vitroandin vivomodels of Alzheimer’s disease
Authors: Trushin Sergey , Nguyen Thi Kim Oanh , Stojacovic Andrea , Ostroot Mark , Deason J. Trey , Chang Su-Youne , Zhang Liang , Macura Slobodan I. , Nambara Toshihiko , Lu Wenyan , Kanekiyo Takahisa , Trushina Eugenia
Published: February 2025

Despite recent approval of monoclonal antibodies that reduce amyloid (Aβ) accumulation, the development of disease-modifying strategies targeting the underlying mechanisms of Alzheimer’s disease (AD) is urgently needed. We demonstrate that mitochondrial complex I (mtCI) represents a druggable target, where its weak inhibition activates neuroprotective signaling, benefiting AD mouse models with Aβ and p-Tau pathologies. Rational design and structure‒activity relationship studies yielded novel mtCI inhibitors profiled in a drug discovery funnel designed to address their safety, selectivity, and efficacy. The new lead compound C458 is highly protective against Aβ toxicity, has favorable pharmacokinetics, and has minimal off-target effects. C458 exhibited excellent brain penetrance, activating neuroprotective pathways with a single dose. Preclinical studies in APP/PS1 mice were conducted via functional tests, metabolic assessment,in vivo31P- NMR spectroscopy, blood cytokine panels,ex vivoelectrophysiology, and Western blotting. Chronic oral administration improved long-term potentiation, reduced oxidative stress and inflammation, and enhanced mitochondrial biogenesis, antioxidant signaling, and cellular energetics. These studies provide further evidence that the restoration of mitochondrial function and brain energetics in response to mild energetic stress represents a promising disease- modifying strategy for AD.
Coordinated macrophage and T cell interactions mediate response to checkpoint blockade in colorectal cancer
Authors: Mestrallet Guillaume , Brown Matthew , Vaninov Natalie , Cho Nam Woo , Velazquez Leandra , Ananthanarayanan Aparna , Spitzer Matthew , Vabret Nicolas , Cimen Bozkus Cansu , Samstein Robert M , Bhardwaj Nina
Published: February 2025

Mismatch repair deficiency (MMRd), either due to inherited or somatic mutation, is prevalent in colorectal cancer (CRC) and other cancers. While anti-PD-1 therapy is utilized in both local and advanced disease, up to 50% of MMRd CRC fail to respond. Using animal and human models of MMRd, we determined that interactions between MHC+ C1Q+ CXCL9+ macrophages and TCF+ BHLHE40+ PRF1+ T cell subsets are associated with control of MMRd tumor growth, during anti-PD-1 treatment. In contrast, resistance is associated with upregulation of TIM3, LAG3, TIGIT, and PD-1 expression on T cells, and infiltration of the tumor with immunosuppressive TREM2+ macrophages and monocytes. By combining anti-PD-1 with anti-LAG3/CTLA4/TREM2, up to 100% tumor eradication was achieved in MMRd CRC and remarkably, in >70% in MMRp CRC. This study identifies key T cell and macrophage subsets mediating the efficacy of immunotherapy in overcoming immune escape in both MMRd and MMRp CRC settings.

Abstract Figure

Highlights

Anti-PD-1 therapy leads to the accumulation and colocalization of MHCI/II+ C1Q+ CXCL9+ macrophages and DCs with TCF+ CCL5+ T cells that have high TCR diversity.

Resistance to anti-PD-1 therapy involves multiple T cell checkpoints, TREM2+ macrophages, IL1B+ TREM1+ monocytes and neutrophils, and IFITM+ tumor cells.

Simultaneous blockade of PD-1, LAG3, CTLA-4 and TREM2 dramatically prevents progression of both MMRd and MMRp tumors.

Combination therapy completely eliminates tumors by leveraging MHC+ macrophage, CD4+ and CD8+ T cell interactions, facilitating durable anti-tumor effects.
IMMUNOGENICITY AND SAFETY OF CHICKEN EMBRYO FIBROBLAST ADAPTED FOWLPOX VACCINE
Authors: Okafor Uchenna Somtochukwu , Israel Stephen , Meseko Clement Adebajo , Adediran Oyeduntan Adejoju , Ogunmolawa Oluyemi Rotimi , Darang Anthony B. , Bwala Dauda Garba
Published: February 2025

Background

The use of chorioallantoic membranes (CAM) route for the propagation of fowlpox virus (FPV) is the method applied in the production of potent and effective fowlpox vaccine at the National Veterinary Research Institute (NVRI), Vom. However, production insufficiency has led to inadequate supply of vaccine to meet farmer’s demands. This has left large number of susceptible and unvaccinated flocks with outbreaks of the disease being reported in Nigerian.

Aim

This study adapted FPV to Chicken embryo fibroblast (CEF) cell culture and assessed its immunogenicity and safety of the resulting vaccine in comparison to a locally produced CAM-based FPV vaccine.

Methods

The FPV were propagated on CAM and CEF of 9 to 12 day old developing chicken embryos. The vaccine harvests were subjected to quality checks, titrated, and used in vaccinating experimental birds via the wing web to monitor for takes, seroconversion, and safety.

Results

The FPV was successful adapted to CEF as demonstrated by the attainment of 80 to 90% cytopathic effect within 71 to 115 hours in the different passages. Both the CEF and CAM-adapted vaccine harvests were highly replicative producing titres of above 106.0/ml TCID50,but higher titres of 108.25/ml TCID50was recorded in the CEF-adapted vaccines. Experimentally vaccinated birds showed 100% takes within 3 to 4 days post-vaccination, with no adverse effects recorded.

Conclusion

This research reported successful development and adaptation of FPV to CEF that was safe and immunogenic, with the potential for its use in the production of self-sufficiency vaccine for fowlpox prevention and control in poultry.
Intraline genomic heterogeneity of the triple-negative breast cancer MDA-MB-231 cell line
Authors: Varela-Rouco Nair , Estévez-Gómez Nuria , Fernández-Santiago Cristóbal , Tomás Laura , Pérez Miriam , García-Souto Daniel , Pasantes Juan Jose , Piñeiro Roberto , Alves João Miguel , Posada David
Published: February 2025

Cancer cell lines are valuable models for studying tumor biology, yet their genomic evolution during culture can compromise experimental reproducibility. We conducted a detailed genomic analysis of the triple-negative breast cancer cell line MDA-MB-231, examining sublines obtained from different sources, at various time points, and across distinct passages. We introduce the concept of intraline heterogeneity (ILH) to highlight the genomic variability observed among these sublines. Our analyses revealed extensive genomic diversity, including differences in single nucleotide variants (SNVs) and copy number alterations (CNAs). In particular, CNAs exhibited remarkable heterogeneity, with pronounced chromosomal gains and losses between sublines, underscoring the impact of genomic instability on ILH. These findings suggest that ILH may influence experimental outcomes, emphasizing the importance of considering passage-specific genomic characterization to ensure consistency and reliability in cancer research.
Single-sample, multi-omic mass spectrometry for investigating mechanisms of drug toxicity
Authors: Mahmud Iqbal , Chan Wai-Kin , Yannell Karen , Simmermaker Cate , Van de Bittner Genevieve , Wu Linfeng , Chan Daniel , Mohsin Sheher Banu , Liu Yiwei , Sausen John , Weinstein John N. , Lorenzi Philip L.
Published: February 2025

Poor therapeutic index is a principal cause of drug attrition during development. A case in point is L-asparaginase (ASNase), an enzyme-drug approved for treatment of pediatric acute lymphoblastic leukemia (ALL) but too toxic for adults. To elucidate potentially targetable mechanisms for mitigation of ASNase toxicity, we performed multi-omic profiling of the response to sub-toxic and toxic doses of ASNase in mice. We collected whole blood samples longitudinally, processed them to plasma, and extracted metabolites, lipids, and proteins from a single 20-µL plasma sample. We analyzed the extracts using multiple reaction monitoring (MRM) of 500+ water soluble metabolites, 750+ lipids, and 375 peptides on a triple quadrupole LC-MS/MS platform. Metabolites, lipids, and peptides that were modulated in a dose-dependent manner appeared to converge on antioxidation, inflammation, autophagy, and cell death pathways, prompting the hypothesis that inhibiting those pathways might decrease ASNase toxicity while preserving anticancer activity. Overall, we provide here a streamlined, three-in-one LC-MS/MS workflow for targeted metabolomics, lipidomics, and proteomics and demonstrate its ability to generate new insights into mechanisms of drug toxicity.
AAV-mediated peripheral single chain variable fragments’ administration to reduce cerebral tau in adult P301S transgenic mice: mono- vs combination therapy
Authors: Katel Sebica , Cicalo Julia , Vasciaveo Valeria , Carrion Joseph , Leann Mahadeo , Huerta Patricio T. , Marambaud Philippe , Giliberto Luca , d’Abramo Cristina
Published: February 2025

Tau is a primary target for immunotherapy in Alzheimer’s disease. Recent studies have shown the potential of anti-tau fragment antibodies in lowering pathological tau levelsin vitroandin vivo. Here, we compared the effects of single-chain variable fragments (scFv) derived from the well-characterized monoclonal antibodies PHF1 and MC1. We used adeno-associated virus 1 (AAV1) to deliver scFvs to skeletal muscle cells in eight-week-old P301S tau transgenic mice. We evaluated motor and behavioral functions at 16 and 23 weeks of age and measured misfolded, soluble, oligomeric and insoluble brain tau species. Monotherapy with scFv-MC1 improved motor and behavioral functions more effectively than scFv-PHF1 or combination therapy. Brain glucose metabolism also benefited from scFv-MC1 treatment. Surprisingly, combining scFvs targeting early (MC1) and late (PHF1) tau modifications did not produce additive or synergistic effects. These results confirm that intramuscular AAV1-mediated scFv-MC1 gene therapy holds promise as a potential treatment for Alzheimer’s disease. Our findings also suggest that combining scFvs targeting different tau epitopes may not necessarily enhance efficacy if administered together in a prevention paradigm. Further research is needed to explore whether other antibodies’ combinations and/or administration schedules could improve the efficacy of scFv-MC1 alone.

Graphical abstract/eTOC synopsis

Katel and colleagues show that peripheral vectorized scFvMC1 (in monotherapy) reduces pathological tau species in tau transgenic mice more efficiently than in combination with scFv-PHF1. The authors observed improved motor and behavioral functions together with increased brain glucose metabolism in scFv-MC1-treated mice.
POCALI: Prediction and insight On CAncer LncRNAs by Integrating multi-omics data with machine learning
Authors: Rao Ziyan , Wu Chenyang , Liao Yunxi , Ye Chuan , Huang Shaodong , Zhao Dongyu
Published: February 2025

Long non-coding RNAs (lncRNAs) are receiving increasing attention as cancer markers for cancer diagnosis and treatment. Although there are many computational methods to identify cancer lncRNAs, they do not comprehensively integrate multi-omics features for predictions or systematically evaluate the contribution of each class of omics to the multifaced landscape of cancer lncRNAs. In this study, we developed an algorithm, POCALI, to identify cancer lncRNAs by integrating 44 omics features across six categories. We explored the contributions of different omics to identifying cancer lncRNAs and, more specifically, how each feature contributes to a single prediction. We also evaluated our model and benchmarked POCALI with existing methods. Finally, we validated the cancer phenotype and genomics characteristics of the novel cancer lncRNAs that were predicted. POCALI identified secondary structure and gene expression-related features as strong predictors of cancer lncRNAs, and epigenomic features as moderate predictors. POCALI performed better than other methods, especially in terms of sensitivity, and predicted more candidates. Novel POCALI-predicted cancer lncRNAs had strong relationships with cancer phenotypes, similar to known cancer lncRNAs. Overall, this study facilitated the identification of previously undetected cancer lncRNAs and the comprehensive exploration of the multifaceted feature contributions to cancer lncRNA prediction.
An RNA Splicing System that Excises Transposons from Animal mRNAs
Authors: Zhao Long-Wen , Nardone Christopher , Paulo Joao A. , Elledge Stephen J. , Kennedy Scott
Published: February 2025

All genomes harbor mobile genetic parasites called transposable elements (TEs). Here we describe a system, which we term SOS splicing, that protectsC. elegansand human genes from DNA transposon-mediated disruption by excising these TEs from host mRNAs. SOS splicing, which operates independently of the spliceosome, is a pattern recognition system triggered by base-pairing of inverted terminal repeat elements, which are a defining feature of the DNA transposons. We identify three factors required for SOS splicing in bothC. elegansand human cells; AKAP17A, which binds TE-containing mRNAs; the RNA ligase RTCB; and CAAP1, which bridges RTCB and AKAP17A, allowing RTCB to ligate mRNA fragments generated by TE excision. We propose that SOS splicing is a novel, conserved, and RNA structure-directed mode of mRNA splicing and that one function of SOS splicing is to genetically buffer animals from the deleterious effects of TE-mediated gene perturbation.
Reducing batch effects in single cell chromatin accessibility measurements by pooled transposition with MULTI-ATAC
Authors: Conrad Daniel N. , Phong Kiet T. , Korotkevich Ekaterina , McGinnis Christopher S. , Zhu Qin , Chow Eric D. , Gartner Zev J.
Published: February 2025

Large-scale scATAC-seq experiments are challenging because of their costs, lengthy protocols, and confounding batch effects. Several sample multiplexing technologies aim to address these challenges, but do not remove batch effects introduced when performing transposition reactions in parallel. We demonstrate that sample-to-sample variability in nuclei-to-Tn5 ratios is a major cause of batch effects and develop MULTI-ATAC, a multiplexing method that pools samples prior to transposition, as a solution. MULTI-ATAC provides high accuracy in sample classification and doublet detection while eliminating batch effects associated with variable nucleus-to-Tn5 ratio. We illustrate the power of MULTI-ATAC by performing a 96-plex multiomic drug assay targeting epigenetic remodelers in a model of primary immune cell activation, uncovering tens of thousands of drug-responsive chromatin regions, cell-type specific effects, and potent differences between matched inhibitors and degraders. MULTI-ATAC therefore enables batch-free and scalable scATAC-seq workflows, providing deeper insights into complex biological processes and potential therapeutic targets.
High Enzyme Promiscuity in Lignin Degradation Mechanisms inRhodopseudomonas palustrisCGA009
Authors: Kathol Mark , Chowdhury Niaz Bahar , Immethun Cheryl , Alsiyabi Adil , Morris Dianna , Naldrett Michael J. , Saha Rajib
Published: February 2025

Lignin is a universal waste product of the agricultural industry and is currently seen as a potential feedstock for more sustainable manufacturing. While it is the second most abundant biopolymer in the world, most of it is currently burned as it is a very recalcitrant material. Many recent studies, however, have demonstrated the viability of biocatalysis to improve the value of this feedstock and convert it into more useful chemicals, such as polyhydroxybutyrate, and clean fuels like hydrogen and n-butanol.Rhodopseudomonas palustrisis a gram-negative bacterium which demonstrates a plethora of desirable metabolic capabilities, including aromatic catabolism useful for lignin degradation. This study uses a multi-omics approach, including the first usage of CRISPRi inR. palustris, to investigate the lignin consumption mechanisms ofR. palustris, the essentiality of redox homeostasis to lignin consumption, elucidate a potential lignin catabolic superpathway, and enable more economically viable sustainable lignin valorization processes.
Diverse Viral Pathogens in Australian Canines: Limited Geographic Structure and the First Detection of an RNA Virus in Dingoes
Authors: Mifsud Jonathon C.O. , Harvey Erin , Brussel Kate Van , Olsson Annabelle , Pitcher Benjamin J. , Hall Jane , Fenton Heather , Alting Brendan F. , Sadiq Sabrina , Holmes Edward C.
Published: February 2025

Viruses impose a substantial disease burden on dogs and the close relationship between dogs and humans may facilitate zoonotic disease emergence. Australia’s geographic isolation, strict biosecurity measures and native dingo populations present a unique model for understanding the spread and evolution of canine viruses. However, aside from a few well-characterised pathogens, genomic data are scarce for many common dog viruses, limiting our understanding of their evolution and disease ecology. Using a metatranscriptomic approach we identified the viruses in dogs and dingoes from various geographical locations across mainland Australia and sample types, revealing 86 vertebrate-associated viruses belonging to 16 distinct species, including a new vesivirus-like species. Many of the viruses identified here have not previously been sequenced in Australia. We identified important dog pathogens associated with canine infectious respiratory disease syndrome—such as canine pneumovirus, canine herpesvirus, and canine respiratory coronavirus—and gastroenteritis, including canine parvovirus, canine coronavirus, and rotavirus A. The sequences of Australian canine viruses often occupied multiple distinct clades phylogenetically and had little geographic structure, suggesting multiple virus introductions and subsequent spread across the country. Notably, we identified the first RNA virus – rotavirus A – in a dingo. This virus was phylogenetically distinct from dog-associated rotavirus A sequences and more closely related to viruses found in humans and bats, indicative of the past cross-species transmission of a reassortant virus into dingoes, and shows dingoes and domestic dogs may have distinct viromes. Our findings expand the knowledge of viral diversity in Australian canines, improving our understanding of viral movement into and within Australia, as well as the potential zoonotic risks associated with dogs and dingoes.
Diatom biodiversity response to shrinking glaciers in the Peruvian Andes
Authors: Kerr Nicky R. , Quincey Duncan , Fell Sarah C. , Kelly Martyn , Medina Katy , Loarte Edwin , Brown Lee E.
Published: February 2025

Alpine river biodiversity is under threat as climate change is driving extensive glacier retreat worldwide, altering aquatic habitats and restructuring biotic communities. However, with the exception of macroinvertebrates, the responses of aquatic groups to deglaciation have received little attention, particularly in tropical ecosystems where species may respond differently owing to additional pressures such as distinct wet and dry seasons, limited snowmelt and extreme high altitude and thus lower oxygen availability. Utilising a continuum of glacier cover across 23 rivers in the Peruvian Andes (Cordilleras Blanca and Vilcanota), we demonstrate that diatoms, abundant primary producers in glacier-fed rivers, show regionally consistent increased α-diversity and density responses with deglaciation. However, β-diversity was found to decline, potentially reflecting the reduction of habitat heterogeneity and niche space both within and between alpine rivers as glaciers are lost. High regional biodiversity, with just 23% of taxa found in both regions, was closely linked to the distinct underlying geologies of the Andes which influence water chemistry. Thirty-eight taxa were found exclusively at sites with glacier cover ≥ 25%, which is considerably higher than numbers recorded in European alpine rivers. However, 31 taxa were identified only at non-glacial sites suggesting deglaciation could open up more habitat for these species. Peruvian rivers overall showed similar responses to glacier retreat as temperate alpine systems, but the large number of taxa found only at mid-high glacial influence sites suggests tropical diatom assemblages may be especially vulnerable to climate change.
Calcite Precipitation by a Nitrogen-Fixing Cyanobacterium
Authors: Brininger Christian M. , Tay Jian Wei , Johnson Evan B. , Espelie Erin , Cameron Jeffrey C.
Published: February 2025

Microbiologically induced calcium carbonate precipitation (MICP) is the process through which the metabolic activity of microorganisms causes the precipitation of calcium carbonate, which can result in solidification of sediment. In cyanobacteria, MICP is thought to occur primarily because cells sequester bicarbonate for the photosynthetic process, thereby lowering the pH of the surrounding media. However, these mechanisms are still poorly understood. Here we show direct evidence of MICP caused by the filamentous cyanobacteriumAnabaena.Anabaenadifferentiates into photosynthetic vegetative cells and nitrogen-fixing heterocysts. Using quantitative microscopy, we show that MICP occurs due to two distinct mechanisms: Firstly, mechanical stress on vegetative cells can cause leakage and/or lysis, releasing sequestered bicarbonate into the environment, resulting in formation of new crystals. Secondly, contact between a heterocyst and a calcite crystal seed appears to cause rapid crystal growth. Our results suggest an evolutionary benefit of contact-mediated precipitation to anchor cyanobacteria growing in tidal regions. By providing greater insight into MICP caused byAnabaena, these results could be used to optimize bio-cement production, thereby enabling a green construction material that could assist with carbon sequestration and reducing the impact of climate change.
Encoded and non-genetic alternative protein variants expand human functional proteome
Authors: Tretyachenko Vyacheslav , Leiman Tehila , Asraf Omer , Dahan Orna , Dahary Dvir , Pilpel Yitzhak
Published: February 2025

Each stage of the Central Dogma contributes to proteome diversity through mechanisms such as heterozygosity, somatic mutations, transcriptional errors, and translational errors. As a result, a diverse array of protein variants can coexist within a single proteome, such as that of humans. However, until now, methods to detect, quantify, and evaluate the functional consequences of these variants have been lacking. Here we examined a large-scale proteogenomic dataset from 29 healthy human tissues and uncovered over 46,000 of unique single amino acid variants co-existing alongside their corresponding reference proteoforms. Our analysis reveals that substitutions preferentially occur in proteins with low expression levels and often affect less frequently encoded amino acids such as tryptophan, cysteine, histidine, or methionine. We found that the abundance of both genetic (SNP’s, somatic mutations) and mistranslated protein variants mirror their allele frequencies in the human population. Moreover, we show that non-genetic substitutions provide a distinct route for exploring protein sequence space, circumventing the mutational constraints imposed by the genetic code. Further, we demonstrate that substitution prevalence correlates negatively with their predicted pathogenicity, particularly in proteins expressed at low levels. We identified hundreds of substituted non-genetic proteoforms that recur consistently in multiple individuals and map to annotated protein functional sites. We propose that these substitutions constitute a novel class of functional protein phenotypic variants. Finally, we illustrate the impact of active-site substitutions in genes such as GAPDH and hemoglobin and highlight potential non-genetic routes of immunoglobulin diversification. Collectively, our findings indicate that non-genetic amino acid substitutions in human proteins provide a recurring and specific route to expanding the functional proteome.
Off-target detection of CRISPR-Cas9 nucleasein vitrowith CROFT-Seq
Authors: Toliusis Paulius , Grybauskas Algirdas , Sinkunas Tomas , Karvelis Tautvydas , Sasnauskas Giedrius , Zaremba Mindaugas
Published: February 2025

Programmable CRISPR-Cas9 nucleases have become invaluable tools for genome editing. However, off-target cleavage by these nucleases could lead to unintended changes in the edited genome. Detection of off-target sites is critical to make genome editing technology safe and predictable. Although currentin vitromethods for off-target detection can identify these sites, they are time-consuming, complex, and relatively costly. Here, we present CROFT-Seq (CRISPR nucleaseoff-target detection bysequencing), a sensitive, rapid, and cost-effective assay for the genome-wide detection of Cas9 off-target sitesin vitro. CROFT-Seq performs comparably to the common currently usedin vitromethods and serves as a valuable and efficient tool for the rapid assessment of genome-editing nuclease specificity. Notably, a high proportion of the top-ranked off-targets identified by CROFT-Seq were validated in cells, highlighting its effectiveness as a predictor of off-target sites.