bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Soilborne Pathogens in High Tunnel Tomato Production in Ohio and Nearby States
Authors: Hamal Manisha , Roman Caterina , Lewis Ivey Melanie , Miller Sally , Gugino Beth K. , Testen Anna Louise
Published: February 2025

Although high tunnels protect against extreme weather conditions, increased soil temperatures and lack of crop rotation within these structures result in the accumulation of soilborne pathogens in tomato (Solanum lycopersicum) production. In Ohio, soilborne diseases occur in a complex of corky root rot (Pseudopyrenochaeta spp.), black dot root rot (Colletotrichum coccodes), Verticillium wilt (Verticillium dahliae) and root-knot nematodes (Meloidogyne spp.). However, this soilborne disease complex has not been assessed in high tunnel tomato production in nearby states. This study sought to evaluate the prevalence of soilborne pathogens in 265 tomato high tunnels on 118 farms from 12 states including Illinois, Indiana, Kentucky, Maine, Maryland, Massachusetts, Michigan, Minnesota, New Hampshire, Ohio, Pennsylvania, and Vermont. Pseudopyrenochaeta spp. were found in 57.4% of high tunnels. Colletotrichum coccodes was detected in 77.7% of high tunnels. Verticillium dahliae was present in 68.3% of high tunnels. Meloidogyne spp. was detected in 62.4% of high tunnels. The prevalence of these diseases highlights the need for proactive soilborne disease management approaches in high tunnels.
Bruton Tyrosine Kinase Degraders
Authors: Sabakhtarishvili Giorgi , Alshebli Mouza , Bajwa Omer , Tabbara Imad A.
Published: February 2025

Bruton tyrosine kinase (BTK) is a key enzyme involved in B-cell development and signaling, making it a crucial target in the treatment of B-cell malignancies, such as chronic lymphocytic leukemia and non-Hodgkin lymphoma. While BTK inhibitors (BTKi), such as ibrutinib, have been effective, resistance—both intrinsic and acquired—poses a significant challenge, often associated with BTK mutations like C481S. To address this, novel BTK degraders have been developed, leveraging proteolysis-targeting chimeras to selectively degrade both wild-type and mutant BTK forms. This approach offers a promising strategy to overcome BTKi resistance.

Agents such as NRX-0492, BGB-16673, NX-5948, NX-2127, HZ-Q1060, ABBV-101, and AC676 have shown significant BTK degradation in preclinical and early clinical trials. NRX-0492 demonstrated over 90% BTK degradation with sustained pharmacodynamic effects, whereas BGB-16673 achieved clinical responses in 67% of patients with relapsed/refractory B-cell malignancies. Similarly, NX-5948 and NX-2127 showed potent BTK degradation, with NX-2127, in addition, targeting immunomodulatory proteins, resulting in partial and stable responses in chronic lymphocytic leukemia and non-Hodgkin lymphoma patients. HZ-Q1060, a preclinical candidate, displayed rapid and sustained BTK degradation in vivo. Early-phase trials of ABBV-101 and AC676 are also showing promising results.

These BTK degraders have demonstrated favorable safety profiles, with manageable adverse events, and offer a novel therapeutic avenue for patients with BTKi-resistant malignancies. As clinical trials progress, these degraders hold the potential to significantly enhance treatment outcomes, offering a new frontier in personalized cancer therapy.
Facility Readiness Assessment for Maternal Immunization: Results of Field Testing in Kenya and Bangladesh
Authors: Noguchi Lisa , Njogu Rosemary , Morgan Christopher , Yunus Samiha , Kabue Mark , Rahman Setara , Annibal Klara , Karron Ruth A.
Published: February 2025

Recent COVID-19 vaccine experience in low- and middle-income countries has suggested many primary care settings are unprepared to administer new vaccines to pregnant and postnatal populations. Deployment of a new maternal vaccine against respiratory syncytial virus (RSV) to protect against RSV lower respiratory illness in the first 6 months of life has accelerated, with vaccination now offered during pregnancy in some high- and middle-income countries. We aimed to design and assess the feasibility of tools for the evaluation of health facility readiness to introduce new vaccines into antenatal care. The health facility assessment tool for maternal immunization readiness was developed with indicators for key health service delivery domains for maternal immunization and piloted in Kenya and Bangladesh. Pilots were conducted from February to April 2022 in Kenya and January 2023 to June 2023 in Bangladesh. The tool proved feasible for administration via audit of records, facility equipment and operations, interview with officer-in-charge and optional modules for structured nonidentifiable observation of antenatal care and immunization services. The pilot exercise surfaced multiple areas for quality improvement action by health systems in Kenya and Bangladesh. In addition to testing the functionality of the tool, data collected during pilot testing were reviewed and presented to participating subnational managers and national technical working groups, allowing these entities to review and discuss initial assessments of gaps and strengths in readiness for new maternal vaccines. A global adaptable version of the tool is now available for contextualization to other settings that are preparing for rollout of new maternal vaccines.
Systematic Literature Review of Maternal Antibodies in Human Milk Following Vaccination During Pregnancy or Lactation: Tetanus, Pertussis, Influenza and COVID-19
Authors: Deese Jennifer , Schaible Kassandra , Massierer Daniela , Tingir Nguhemen , Fell Deshayne B. , Atwell Jessica E.
Published: February 2025

Background:

Human milk (HM) contributes to infant disease protection through transfer of numerous bioactive molecules, including antibodies, though the mechanisms that determine HM antibody transfer and disease prevention in the infant are not fully understood. Even less is known about the transfer of, and infant protection afforded by, vaccine-induced HM antibodies following vaccination during pregnancy or lactation. This systematic literature review aimed to summarize published evidence on the presence, duration and function of HM antibodies against pertussis, influenza and coronavirus disease 2019 (COVID-19) induced by vaccination during pregnancy or lactation and the associated protection against infant illness and to identify gaps to guide future research in this area.

Methods:

Literature searches were conducted on September 15, 2023, in MEDLINE and Embase for articles published since January 2000.

Results:

Eighteen studies reporting vaccine-induced antibodies in HM or protection against infant illness were included. The collective evidence supports increased and sustained HM antibody levels following influenza and COVID-19 vaccination while antipertussis HM antibody levels remained elevated for only approximately 4 weeks postvaccination. COVID-19 booster vaccination during pregnancy was found to prolong the half-life of immunoglobulin G antibodies in HM relative to the COVID-19 primary vaccination series. Only 2 studies evaluated illness among breastfed infants born to mothers vaccinated during pregnancy; however, neither distinguished the independent effects of transplacental transfer of vaccine-induced antibodies, HM transfer of vaccine-induced antibodies and HM transfer of naturally acquired antibodies.

Conclusions:

HM antibody levels are increased following pertussis, influenza and COVID-19 vaccination during pregnancy or lactation. However, the limited evidence base precludes conclusions about any incremental benefit of breastfeeding following vaccination during pregnancy versus the benefit of breastfeeding alone and studies designed to address this question are needed to inform vaccine policy.
Informing Maternal Immunization Trials: An Observational Study to Assess Background Rates of Maternal, Pregnancy, and Neonatal/Infant Outcomes
Authors: Hsiao Amber , Zerbo Ousseny , Hansen John , Timbol Julius , Lewis Ned , Li Se , Pu Wenji , Tullio Antonella N. , Klein Nicola P.
Published: February 2025

Background:

Pregnant individuals have been historically excluded from clinical trials. To evaluate the safety of vaccines in pregnant individuals and their infants, more data on expected ranges of background rates of pregnancy-related outcomes of interest are needed. The objective of this real-world observational study was to assess background rates of maternal, pregnancy and neonatal/infant outcomes in pregnant individuals and their infants.

Methods:

We conducted a retrospective observational cohort study of pregnant individuals and their infants using data from Kaiser Permanente Northern California from January 1, 2007, to December 31, 2018. We assessed the incidence proportions of 17 maternal, 4 pregnancy and 10 neonatal/infant outcomes of interest, including eclampsia, preterm labor and stillbirths. Incidence proportions were stratified by maternal age group, race/ethnicity and insurance type.

Results:

There were 415,074 singleton pregnancies and 413,488 singleton live births included in the study. The most common adverse outcomes (>10%) were preterm labor, gestational diabetes, minor congenital anomalies, macrosomia and large for gestational age. The proportions for pregnancy-related hypertension, fetal asphyxia and preeclampsia were also relatively high (between 5% and 7%). Pregnant individuals (and their infants) in the youngest and oldest age groups, and those of Black race, had the highest proportions for nearly all outcomes.

Conclusions:

Overall, the proportions of the outcomes assessed were generally consistent with previously published literature of pregnant individuals and their infants in the United States (US). The study provides background rates of important maternal, pregnancy and neonatal/infant outcomes in a US population that may inform vaccine clinical trials and vaccine safety studies in pregnant individuals.
Assessing Vaccine Coverage and Barriers to Immunization Among Pregnant Individuals in Uruguay: A Brief Report
Authors: Paladino Beatriz , Delfino Marcos , Badia Federica , Pujadas Monica , Pírez Catalina
Published: February 2025

This study evaluates vaccine coverage rates and identifies barriers to influenza and pertussis immunization among pregnant individuals in Uruguay. Despite free and accessible vaccination, coverage remains low due to lack of medical recommendations and unawareness. Enhancing healthcare professional training and public awareness is essential to improve immunization rates and safeguard maternal and infant health.
Impact of HIV Status on Group B Streptococcus Colonization and Antibody Responses in Serum and Vaginal Mucosa
Authors: Daniel Olwenn , Nalwoga Joannah , Kyohere Mary , Nsimire Sendagala Juliet , Imede Esther , Beach Simon , Barro Camille , Tharmarasa Thushani , Hall Tom , Cochet Madeleine , Tregoning John , Le Doare Kirsty
Published: February 2025

Background:

Group B streptococcus (GBS) is a commensal bacterium of the digestive and genital tracts that can occasionally cause maternal and neonatal disease. GBS is particularly a burden in low-resource settings, where infections with HIV are also highly prevalent. This study investigates the impact of HIV status on GBS colonization and antibody levels.

Methods:

In Uganda, 90 nonpregnant women of childbearing age were followed for 3 months. Every 2 weeks, rectal and vaginal swabs were tested for GBS, and vaginal cups and blood were collected for measurement of GBS capsular polysaccharides (CPS) IgG using standardized assays.

Results:

Twenty-six of 90 women were living with HIV. Almost 51/90 women were GBS colonized at 1 or several visits. GBS colonization fluctuated in the rectal and vaginal sites. Most prevalent serotypes were Ia and III, with 33 individuals carrying different serotypes over time. Serum and vaginal CPS-IgG levels were stable over 12 weeks. In serum, for serotypes Ib–V, the geometric mean concentration (GMC) of CPS-IgG did not differ between HIV+ and HIV− participants. However, the GMC for serum CPS-Ia-IgG in the HIV+ group was 2.5 times lower than in the HIV− group (P = 0.038). Vaginal CPS-IgG was measurable in 5/26 (19%) HIV+ participants, and 32/64 (50%) HIV− participants.

Conclusions:

Despite fluctuating GBS colonization, antibody levels remained stable over 12 weeks. The level of CPS-Ia-specific IgG in serum was lower in women with HIV than in those without HIV. Vaginal CPS-specific IgG was not measurable in 81% of individuals with HIV.
Clinical Practice Guidelines for the Management of Congenital Syphilis in Japan, 2023: Executive Summary
Authors: Ito Yoshinori , Yamagishi Takuya , Ikenoue Chiaki , Ishiwada Naruhiko , Ito Kenta , Iwatani Sota , Ouchi Kazunobu , Kawana Kei , Shimizu Hiroyuki , Shinjoh Masayoshi , Takeuchi Noriko , Tsugawa Takeshi , Funaki Takanori , Furuichi Munehiro , Hoshino Tadashi , Mikamo Hiroshige , Miyairi Isao , Moriuchi Hiroyuki , Morioka Ichiro , Yamagishi Yuka , Mori Masaaki
Published: February 2025

Congenital syphilis (CS) is a mother-to-child infection caused by the bacterium Treponema pallidum, transmitted through the placenta. In Japan, the number of syphilis cases has recently increased, accompanied by an increase in CS cases. Thus, automated methods for serum antibodies with serial values, without a 2× dilution sequence, have been widely used. Moreover, benzathine penicillin G was introduced in Japan in 2021. In response to the recent surge in CS, the first edition of the clinical practice guidelines for the management of CS was developed by a committee comprising representatives from 4 Japanese medical societies. This summary outlines 5 clinical questions with statements and expert comments regarding diagnosis, treatment and follow-up requirements. These guidelines aim to assist in the management of patients with CS infection.
Current Evidence in Knee-Ankle-Foot Orthosis Therapy for Patients with Stroke: A Systematic Review of Observational Studies
Authors: Kobayashi Eiji , Hiratsuka Kenta , Haruna Hirokazu , Kojima Nobue , Himuro Nobuaki
Published: February 2025

Introduction

Although knee-ankle-foot orthosis (KAFO) therapy is considered effective for improving functional mobility in patients with stroke, the certainty of the evidence remains unclear.

Objective

The aim of this study was to determine the certainty of evidence of treatment effect of KAFO therapy, the methodological quality, and the current status of KAFO therapy in patients with stroke based on existing research.

Methods

Data from studies that examined the treatment effect of KAFO on functional mobility or activities of daily living in patients with stroke were searched on seven databases: PubMed, CINAHL, Scopus, CENTRAL, PEDro, WoS, and Igaku Chuo Zassi. The results were reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. The overall status of KAFO therapy was summarized descriptively. The certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Methodological quality was assessed using the STROBE statement.

Results

Three observational studies were included in the analysis, but no random controlled trials (RCTs) were identified. The certainty of the evidence for treatment effect of KAFO therapy in stroke was very low. The included studies did not adequately control potential confounders. The treatment effects of KAFO therapy for different levels of lower-limb paralysis and those on walking ability outcomes remain unclear.

Conclusions

The lack of RCTs limits the evidence for the treatment effect of KAFO therapy in patients with stroke. This systematic review of observational studies highlights the low certainty of current evidence and identifies key areas for improvement in future research.

Clinical Relevance

This is the first systematic review of observational studies to elucidate current evidence of the treatment effect of KAFOs in patients with stroke. KAFOs may improve functional mobility and activities of daily living; however, the certainty of the evidence is very low, and high-quality trials are needed to establish the benefits of KAFO therapy for these patients.
Automated Technical Skill and Performance Assessment in Otology and Neurotology: A Scoping Review
Authors: Nwosu Obinna I. , Ota Mitsuki , Goss Deborah , Crowson Matthew G.
Published: February 2025

Objectives/Hypothesis

This scoping review aims to provide an overview of existing semi-automated and fully automated methods for technical skill and performance assessment in otologic and neurotologic procedures.

Study Design

Scoping review.

Databases Reviewed

Ovid MEDLINE (PubMed), Ovid EMBASE, Web of Science Core Collection, and IEEE Xplor Digital Library.

Methods

A literature search was conducted according to PRISMA-ScR. Included studies were full-text articles that detailed an automated method of technical skill and performance assessment in otologic/neurotologic procedures. Extracted elements included general study characteristics (publication year, study objective, validity type, surgical procedure, and setting) and assessment approach characteristics (method of analysis, metrics assessed, source of metric data, degree of automation, and use of artificial intelligence [AI]).

Results

A total of 1,141 studies were identified from the literature search. After deduplication, title/abstract screening, and full-text review, 21 studies met the inclusion criteria. All but one of the included studies focused on mastoidectomy. Most studies assessed performance exclusively in VR-simulated mastoidectomy (n = 12) as opposed to cadaveric, 3D-printed, or live dissections. The majority of studies concentrated on establishing internal validity of their assessment methods (n = 13). Performance metrics were primarily obtained through motion analysis and final product analysis. Only a minority of studies used AI, which typically involved machine learning regression or classification to predict skill levels based on automatically extracted metrics.

Conclusion

This scoping review explores the developing landscape of automated technical skill and performance assessment in otology and neurotology. Though progress has been made in automating assessment in the field, most investigations are narrowly focused on performance in VR-simulated mastoidectomy and lack external validity evidence. AI and computer vision (CV), which have advanced automated assessment in other surgical fields, have been underutilized in assessing performance in otology and neurotology. Future work must explore the development and validation of automated assessment approaches across a wider range of otologic and neurotologic procedures. Incorporation of novel AI/CV techniques may facilitate real-time integration of automated assessment in a broader range of simulated procedures and live surgical settings.
Scoping review: Intervention for ocular motor disorders in children and adults with mild traumatic brain injury
Authors: Chen Angela M. , Salzano Aaron D. , Burgher Allegra P. , Greenspan Lynn D. , Yap Tiong Peng , Theis Jacqueline , Liu Su-Hsun , Scheiman Mitchell , Roberts Tawna L.
Published: February 2025

SIGNIFICANCE

Intervention strategies for post–mild traumatic brain injury (mTBI) ocular motor disorders vary across disciplines and include watchful waiting, vestibular rehabilitation, vision rehabilitation/vision therapy, and optical intervention. However, evidence supporting their effectiveness is limited, highlighting the need for high-quality randomized controlled trials with standardized testing, diagnostic criteria, and reassessment of ocular motor function after intervention.

BACKGROUND

Ocular motor disorders occur frequently after mTBI.

OBJECTIVES

This study aimed to conduct a scoping review of interventions for mTBI-related ocular motor disorders in children and adults.

DATA SOURCES

The following electronic bibliographic databases were searched: PubMed, Embase, PEDro, OVID, Clinical Key, Google Scholar, and REHABDATA.

STUDY SELECTION

Intervention studies published in English between 2003 and 2024 involving mTBI participants who had an ocular motor assessment prior to intervention were included in this study.

DATA EXTRACTION AND SYNTHESIS

Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines were followed for reporting. Study population, intervention, and outcomes were extracted and synthesized in tabular and graphical formats.

RESULTS

Sixty-seven eligible studies were included, with only three (4%) judged as low risk of bias. Intervention strategies included watchful waiting (n = 31, 46%), vestibular rehabilitation (n = 13, 19%), vision rehabilitation/vision therapy (n = 10, 15%), optical intervention (n = 4, 6%), and alternative interventions or multifaceted interventions (n = 9, 14%). Among the studies providing statistically supported results, improvements in one or more ocular motor outcome domains were reported in nearly 80% of the studies on watchful waiting (19/24) and 100% of the studies on vestibular rehabilitation (4/4), vision rehabilitation/vision therapy (7/7), or optical intervention (1/1).

CONCLUSIONS AND IMPLICATIONS

Although post-mTBI ocular motor deficits improved with watchful waiting strategy, vestibular rehabilitation, vision rehabilitation/vision therapy, and optical interventions, most studies had significant risk of bias. This review emphasizes the necessity for high-quality randomized controlled trials with standardized testing protocols and diagnostic criteria and reassessment of ocular motor functions after intervention to evaluate the effectiveness of these interventions in different age groups and recovery stages.
Network Medicine as a Tool to Enhance Regenerative Rehabilitation Practice
Authors: Iijima Hirotaka , Ambrosio Fabrisia
Published: February 2025

Objective

The aim of the study was to demonstrate the utility of network medicine for enhancing regenerative rehabilitation approaches.

Design

We employed a scientometric approach to illustrate the scientific evolution of regenerative rehabilitation and network medicine over the past 20 yrs. We then present two exemplars of a novel application of network medicine, first to optimize the development of a multimodal rehabilitation program for osteoarthritis and, second, to demonstrate the potential utility of a regenerative rehabilitation protocol for neurological applications.

Results

The scientometric analysis revealed thematic clusters guiding the fields of regenerative rehabilitation, while also revealing a notable gap in the integration of advanced computational biology tools, such as network medicine. To address this gap, we applied a network medicine paradigm as a proof-of-principle in rehabilitation, demonstrating its ability to predict previously known combinational benefits of a multimodal rehabilitation protocol for osteoarthritis and potential of a regenerative rehabilitation protocol to enhance outcomes after stroke.

Conclusions

The trajectory of progress in regenerative rehabilitation has been defined by embracing new technologies and approaches. We propose that network medicine is a new frontier for the field. Toward the design of efficient and optimized clinical protocols, we anticipate that the network medicine paradigm may have broad applications in the field of rehabilitation, even beyond the examples presented here.
Soluble CD14 and IL-12p70 on early ART predict HIV load setpoint after treatment interruption
Authors: van Paassen Pien M. , Boyd Anders C. , Pasternak Alexander O. , Maurer Irma , Harskamp Agnes M. , Grijsen Marlous L. , Jurriaans Suzanne , Prins Jan M. , Kootstra Neeltje A. , de Bree Godelieve J.
Published: February 2025

Objective

After analytical treatment interruption (ATI), viral rebound occurs in most people with HIV. The time to viral rebound (TTVR) is likely determined by the properties of the viral reservoir as well as the anti-viral immune response. Soluble biomarkers of immune activation may be predictive of TTVR and plasma viral load (pVL) setpoint after ATI. The objective of this study is to identify these soluble biomarkers.

Design

A retrospective biomarker analysis of the Primo-SHM trial who were treated 24 or 60 weeks during early HIV infection.

Methods

Thirty-five biomarkers were measured at ATI in 65 participants. Association between biomarkers and reservoir size, TTVR and pVL at setpoint was assessed.

Results

SCD14 correlated to pVL setpoint (B = 0.598; p = 0.004) and lower levels of IL-12p70 to a higher level of pVL setpoint (B = -0.448; p = 0.04). SCD163 correlated to levels of total HIV-DNA (B = 0.413; p = 0.007).

Conclusions

An increased pVL setpoint was associated with higher sCD14 and lower IL12-p70 at ATI and increased total HIV-DNA was associated with higher sCD163 at ATI. SCD14 and sCD163 are biomarkers of monocyte activation, while IL12-p70, produced by monocytes, is essential for inducing Th1 responses. This underscores the relation between immune activation and diminished immune control of HIV. Our findings indicate that sCD14 and IL-12p70 could serve as predictive biomarkers for favorable outcomes in cure interventions.
Safety and Feasibility of Early Extubation in Liver Transplantation: Experience in 1555 Patients
Authors: Lacom Conrad , Kothari Rishi P. , Mendez Nicholas V. , Galli Alessandro , Roll Garrett R. , Bokoch Michael P. , Legrand Matthieu , Adelmann Dieter
Published: February 2025

Background.

Early extubation after liver transplantation can decrease cost and intensive care unit lengths of stay, but its adoption remains limited because of safety concerns. We assessed the feasibility and safety of early extubation at a liver transplant center with a high early extubation rate. We analyzed subgroups of high-risk patients, including high model for end-stage liver disease-sodium (MELD-Na) score, high intraoperative blood loss, and patients undergoing simultaneous liver-kidney transplantation.

Methods.

We included all adult liver transplantations performed at a single center between June 2012 and July 2022. Patients were divided into 2 groups: (1) those extubated early (ie, in the operating room or within the first hour of intensive care unit admission) and (2) those who underwent delayed extubation. The primary outcome was reintubation within 48 h after early extubation. Rates of early extubation were analyzed separately for quartiles of MELD-Na score and intraoperative blood loss.

Results.

Of 1555 patients, 969 (62%) were extubated early. Of these, 31 patients (3.2%) required mechanical ventilation within 48 h postoperatively: 11 patients (1.1%) were reintubated for respiratory failure and 20 (2.1%) remained intubated after reoperation. There was no difference in postoperative pneumonia between the groups (P = 0.059). Early extubation rates inversely correlated with the quartiles of MELD-Na score and estimated blood loss. In the highest quartile for MELD-Na (>34) and estimated blood loss (>5 L), 34% of patients were extubated early.

Conclusions.

Early extubation of properly selected patients after liver transplantation is safe and associated with a low rate of reintubation, even among select groups of high-risk patients.
Improved Microbubble Tracking for Super-Resolution Ultrasound Localization Microscopy using a Bi-Directional Long Short-term Memory Neural Network
Authors: Chen Xi , Lowerison Matthew R. , Shin YiRang , Wang Yike , Dong Zhijie , You Qi , Song Pengfei
Published: February 2025

Ultrasound localization microscopy (ULM) enabled high-accuracy measurements of microvessel flow beyond the resolution limit of conventional ultrasound imaging by utilizing contrast microbubbles (MBs) as point targets. Robust tracking of MBs is an essential task for fast and high-quality ULM image reconstruction. Existing MB tracking methods suffer from challenging imaging scenarios such as high-density MB distributions, fast blood flow, and complex flow dynamics. Here we present a deep learning-based MB pairing and tracking method based on a bi-directional long short-term memory neural network for ULM. The proposed method integrates multiparametric MB characteristics to facilitate more robust and accurate MB pairing and tracking. The method was validated on a simulation data set, a tissue-mimicking flow phantom, andin vivoon a mouse and rat brain.
SpaceBar enables clone tracing in spatial transcriptomic data
Authors: Kinsler Grant , Fagan Caitlin , Li Haiyin , Kaster Jessica , Dunne Maggie , Vander Velde Robert J. , Boe Ryan H. , Shaffer Sydney , Herlyn Meenhard , Raj Arjun , Heyman Yael
Published: February 2025

We report a cellular barcoding strategy, SpaceBar, that enables simultaneous clone tracing and spatial transcriptomics profiling. Our approach uses a library of 96 synthetic barcode sequences that can be robustly detected by imaging based spatial transcriptomics (seqFISH), delivered such that each cell is labeled with a combination of barcodes. We used these barcodes to label melanoma cells in a tumor xenograft model and profiled both clone identity and spatial gene expressionin situ. We developed a gene scoring metric that quantifies how strongly gene expression is driven by intrinsic cellular cues or extrinsic environmental signals. Our framework distinguishes between clonal dynamics and environmentally-driven transcriptional regulation in complex tissue contexts.
Genetic Variants that Modulate Alzheimer’s Disease Risk Deregulate Protein-Protein Correlations in the Gyrus Temporalis Medius
Authors: Bouland Gerard A. , Tesi Niccolò , Zhang Meng , Ganz Andrea B. , Hulsman Marc , van der Lee Sven , Graat Marieke , Rozemuller Annemieke , Huisman Martijn , van Schoor Natasja M. , van der Flier Wiesje M. , Hoozemans Jeroen , Smit August B , Reinders Marcel J.T. , Holstege Henne
Published: February 2025

We conducted a comprehensive protein quantitative trait loci (pQTL) analysis on a unique set of Gyrus Temporalis Medius (GTM) samples obtained from 88 Alzheimer’s Disease (AD) patients, 53 non-demented individuals, and 49 cognitively healthy centenarians. This investigation revealed 8,081 genetic variants associated with the abundance of 227 proteins, including several novel variant-protein links not identified in a prior pQTL study of the prefrontal cortex or expression QTL (eQTL) analysis across 12 brain regions (GTEx). Among all the AD risk variants tested for possible pQTL effects, only rs429358-T (which encodes the APOE4 allele) was significantly linked to higher APOE levels in the GTM, potentially explaining why this region is particularly prone to AD pathology. Further, through differential correlation analysis we identified AD risk variants linked to altered protein-protein correlations, specifically rs9381040 in TREML2, rs34173062 in SHARPIN, and rs11218343 near SORL1. Notably, DDX17 appears to play a protective role in individuals with the rs9381040-T/T genotype by tightly regulating synuclein levels. Collectively, these findings demonstrate that AD risk variants disrupt protein–protein interactions, highlighting a genetic basis for the coordinated modulation of protein networks in AD.
Seroprevalence of Immunoglobulin G against measles and rubella over a 12-year period (2009 – 2021) in Kilifi, Kenya and the impact of the Measles-Rubella (MR) Vaccine campaign of 2016
Authors: Mburu CN , Ojal J , Selim R , Ombati R , Akech D , Karia B , Tuju J , Sigilai A , Smits G , van Gageldonk PGM , van der Klis FRM , Flasche S , Kagucia EW , Scott JAG , Adetifa IMO
Published: February 2025

Background

Measles and rubella have been targeted for elimination by the World Health Organization. Age-specific population immunity to measles and rubella is important to assess progress towards elimination but data are scarce. We conducted seroprevalence surveys to identify disease-specific population immunity profiles in children and adults in Kilifi.

Methods

Sera from cross-sectional surveys in the Kilifi Health Demographic Surveillance System (2009–2021) were analysed using a fluorescent bead-based multiplex immunoassay. Bayesian multilevel regression with post stratification was used to obtain seroprevalence estimates adjusted for the underlying population and assay performance. Associations between seropositivity and age, sex, location and ethnic group were assessed using a mixed effects logistic regression.

Results

Measles-adjusted seroprevalence showed a significant increase from 88% in 2009 to 93% in 2021 (τ = 0.875, P = 0.01). Seropositivity was significantly higher in all age groups compared to those under 9 months. Seroprevalence among children ineligible for the first measles vaccine dose (MCV1) remained low (10–57%), whereas MCV1-eligible children (9–17 months) had higher seroprevalence (68–91%). Adult measles seroprevalence exceeded 96%. Rubella seroprevalence followed a similar pattern, with adults above 88%. Following the MR campaign, measles seroprevalence increased from 92% to 96% in eligible children, while rubella seroprevalence rose from 45% to 82%

Conclusion

Population immunity for measles significantly increased over the 12-year period suggesting improvement in immunisation program performance. To reduce reliance on frequent SIAs, efforts should focus on optimising both the timing and coverage of routine doses, particularly ensuring higher coverage of MCV2. The introduction of rubella vaccination has positively impacted immunity in children. Sustaining this immunity is essential to prevent potential gaps in older age groups, which could increase the risk of Congenital Rubella Syndrome (CRS) in infants
Characterization of transcriptomic changes acrossCoccidioidesmorphologies using RiboMarker®-enhanced RNA sequencing
Authors: Howard Jonathan M. , Manning Aidan C. , Clark Rachel C. , Williams Tahirah , Nobile Clarissa J. , Kazakov Sergei , Barberan-Soler Sergio
Published: February 2025

Coccidioidesis a dimorphic, pathogenic fungus responsible for transmission of the mammalian disease colloquially known as “Valley fever”. To better understand the molecular basis ofCoccidioidespathogenesis, previous studies have characterized transcriptomes that define transitions between the saprobic and pathogenic life stages of the two species that cause Valley fever -Coccidioides immitis and Coccidioides posadasii. However, none of these studies have focused on small RNA profiles, which have been shown in several pathogenic fungi to play crucial roles in host-pathogen communication, affecting virulence and infectivity. In this study, we analyzed changes in small RNA expression across three major morphologies ofC. posadasii: arthroconidia, mycelia, and spherules, from both intracellular and extracellular fractions. Utilizing RiboMarker® small RNA and RNA fragment library preparation, we show enhanced coverage across the transcriptome by increasing incorporation of normally incompatible RNAs into the sequencing pool. Using these data, we observed transcriptomic shifts during the transition of arthroconidia to either mycelia or spherules, marked largely by changes in both protein-coding, tRNA, and unannotated loci. As little is known regarding the mechanisms governing these life stage transitions, these data provide better insight into those small RNA- and fragment-producing genes and loci that may be required for progression betweenCoccidioidessaprobic and parasitic life cycles. Additionally, analysis of fragmentation patterns across all morphologies suggests unique patterns of RNA fragmentation across a cohort of RNA species that correlate with a given ecotype. Finally, we noted evidence of RNA export to the extracellular space, particularly regarding snRNA and tRNA-derived fragments as well as mRNA-derived transcripts, during the transition to either mycelia or spherules, which may play roles in cell-cell, and/or host-pathogen communication. Going forward, this newly established intra- and extracellularCoccidioidessRNA atlas will provide a foundation for potential biomarker discovery and contribute to our understanding of the molecular basis for virulence in Valley fever.
Expanding plant trait databases using large language model: A case study on flower color extraction
Authors: Bamba Masaru , Sato Shusei
Published: February 2025

Plant trait databases play a crucial role in understanding ecological and evolutionary processes yet remain insufficient due to geographical and data availability limitations. To address this limitation, we developed a novel large-scale text extraction approach using a large language model (LLM) to transform descriptions of Floras into structured trait data, thereby expanding existing databases.

We applied this approach to extract flower color information from theFlora of Chinaand integrate it into the TRY Plant Trait Database. After integration, the dataset expanded to 27,252 species, more than doubling the previously available flower color records. Additionally, we linked the dataset with occurrence records from GBIF and environmental data, including climate and soil properties, to disentangle ecological insight and flower color distribution.

Our large-scale association analysis of flower colors and environments revealed that white, yellow, and red-type flowers exhibit distinct environments, suggesting that abiotic environment can play a role in flower color evolution.

By transforming descriptions of Flora into structured data, our approach organizes traits across more plant species, creating new opportunities for ecological and evolutionary research. The present approach can be extended to other traits, enhancing our understanding of how plants adapt and respond to environmental changes on a global scale.
Bacteria break through one-micrometer-square passages by flagellar wrapping
Authors: Yoshioka Aoba , Shimada Yoshiki Y. , Omori Toshihiro , Uemura Naoki A. , Takeshita Kazutaka , Ishigami Kota , Morimura Hiroyuki , Furubayashi Maiko , Kan Tetsuo , Wada Hirofumi , Kikuchi Yoshitomo , Nakane Daisuke
Published: February 2025

intestinal crypts, yet little is known about how bacteria behave under such conditions where movement is challenging due to limited diffusion. Stinkbug symbiontCaballeronia insecticolanavigates a narrow gut passage about one micrometer in diameter to reach the stinkbug's symbiotic organ. Here, we developed a microfluidic device mimicking the host's sorting organ, wherein bacterial cells are confined in a quasi-one-dimensional fashion, and revealed that this bacterium wraps flagellar filaments around its cell body like a screw thread to control fluid flow and generate propulsion for smooth and directional movement in narrow passages. Physical simulations and genetic experiments revealed that hook flexibility is essential for this wrapping; increasing hook rigidity impaired both wrapping motility and infectivity. Thus, flagellar wrapping likely represents an evolutionary innovation, enabling bacteria to break through confined environments using their motility machinery.
An antisense oligomer conjugate with unpredicted bactericidal activity againstFusobacterium nucleatum
Authors: Cosi Valentina , Jung Jakob , Popella Linda , Ponath Falk , Ghosh Chandradhish , Barquist Lars , Vogel Jörg
Published: February 2025

Fusobacteria are commensal members of the oral microbiome that can spread from their primary niche and colonize distal sites in the human body. Their enrichment in colorectal and breast cancer tissue has been associated with tumor growth, metastasis, and chemotherapeutic resistance. The use of non-selective antibiotics to remove fusobacteria impairs tumor progression, but prolonged application risks side effects such as gastrointestinal problems and dysbiosis. Species-specific antisense antibiotics based on peptide nucleic acid (PNA) have shown efficacy in many Gram-negative species, suggesting that antisense PNAs may also enable a tailored depletion of fusobacteria. Here, we have investigated the antibacterial potential of cell-penetrating peptide (CPP)-PNA conjugates targeting the mRNA of putative essential genes inFusobacterium nucleatum. Unexpectedly, we observed no growth inhibition with any of the target-specific PNAs, but identified a non-targeting control CPP-PNA (FUS79, (RXR)4XB-GACATAATTGT) as a potent growth inhibitor ofF. nucleatum. Our data suggest that the CPP and specific sequence features of FUS79 are responsible for its activity, rather than an antisense effect. Interestingly, FUS79 also inhibits the growth of five additional fusobacterial strains but not ofF. nucleatumssp.vincentii(FNV). RNA-seq analysis indicates that FUS79 induces a membrane stress response in a vulnerableF. nucleatumstrain but not in FNV. Collectively, our attempt at developing antisense antibiotics for fusobacteria discovers a potent growth inhibitor, whose bactericidal effect appears independent of target-specific mRNA inhibition.

IMPORTANCE

Enrichment ofF. nucleatumat cancer sites is associated with increased tumor growth and metastasis. Antibiotic treatment to remove the bacteria was shown to change the course of cancer progression. Here we explore first steps to establish peptide nucleic acids (PNAs) as specific antisense antibiotics, thereby laying the foundation for further development of antisense technology in fusobacteria. While the CPP-PNA FUS79 was initially designed as a control, we observed that the compound was bactericidal for specific fusobacterial strains. Our results suggest that FUS79 might be able to selectively deplete fusobacterial strains from bacterial communities, offering a new perspective on fusobacterial removal at the tumor site.
Comparative Computational Docking Analysis of MPP+ and Dopamine Binding to Dopamine Transporter in Human and Zebrafish: Mechanistic Insights into MPTP Neurotoxicity
Authors: Razali Khairiah , Kumar Jaya , Mohamed Wael M. Y.
Published: February 2025

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces parkinsonism via its toxic metabolite, 1-methyl-4-phenylpyridinium (MPP+), which structurally mimics dopamine and enters dopaminergic neurons via the dopamine transporter (DAT). To visually depict this mimicry, we performed ligand-protein docking analysis on two species: humans and zebrafish. Human DAT (PDB ID: Q01959) and zebrafish DAT (UniProt ID: Q90ZV1) proteins were prepared with AutoDock Tools. Meanwhile, MPP+ (PubChem ID: CID_39484) and dopamine (PubChem ID: CID_681) ligands were prepared and optimized using the General AMBER Force Field (GAFF) tool. Docking with AutoDock Vina used identical grid parameters of 40 x 40 x 40 Å, which allows blind docking. Binding affinities and interactions were analyzed and visualized using PyMol and LigPlot+. MPP+ exhibited comparable binding affinities to dopamine in both species (human: -7.2 vs -6.1 kcal/mol; zebrafish: -7.6 vs -6.4 kcal/mol), sharing seven out of nine binding residues in humans and nine out of twelve in zebrafish. Spatial overlap with dopamine binding site suggests MPP+ exploits DAT for neuronal entry. However, static docking limitations warrant dynamic validation. This study provides computational evidence for the dopamine-mimetic mechanism of MPP+ but underscores the need for molecular dynamics (MD) simulation and experimental confirmation.
Degradation of ribosomal RNA duringPlasmodium falciparumgametocytogenesis
Authors: Grünebast Janne , Singhal Ritwik , Bromley Robin , Kanatani Sachie , Watson Kaylee , Dumetz Franck , Pascini Tales Vicari , Tripathi Abhai , Dunning Hotopp Julie C , Sinnis Photini , Llinás Manuel , Serre David
Published: February 2025

The life cycle ofPlasmodium falciparumis characterized by complex regulatory changes that allow adaptation of the parasites to different environmental conditions, which are especially pronounced during transmission between the mammalian host and the insect vector. Previous studies have shown thatP. falciparumuses three types of ribosomal RNAs (rRNA A-, S1- and S2-types) at different stages of its life cycle. We used Oxford Nanopore Technologies (ONT) direct RNA sequencing to investigate the dynamics of rRNA usage throughout the parasite’s intraerythrocytic development, as well as in salivary gland sporozoites. Our study revealed a preponderance of A-type rRNAs during the intraerythrocytic cycle and gametocytogenesis, while S-type rRNAs slowly increase in abundance in mosquito stages starting three days post infection. Salivary gland sporozoites showed an even proportion of all rRNA types. By examining the length distributions of rRNA molecules, we detected an extensive and specific degradation of rRNAs during gametocytogenesis, starting in stage II gametocytes and continuing until the final stages of gametocyte development. We hypothesize that rRNA degradation may be linked to the global translational repression and metabolic quiescence described in stage V gametocytes, similar to mechanisms observed in bacterial and eukaryotic stress responses.
Annexin A1 as a key modulator of lung inflammation during coronavirus infections
Authors: Resende Filipe , Queiroz-Junior Celso Martins , Ascenção Fernando Roque , Chaves Ian de Meira , Lacerda Larisse de Souza Barbosa , Rocha Felipe , Teixeira Danielle , Galvão Izabela , Costa Victor , Fonseca Talita , Gualberto Arthur , Santos Ana Luiza de Castro , Martins Jenniffer , Lima Erick Bryan de Sousa , Monteiro Adelson Héric Alves , Zaidan Isabella , Grossi Laís C. , Costa Pedro Augusto Carvalho , Beltrami Vinicius Amorim , Sousa Lirlândia P. , Guimarães Pedro Pires Goulart , Campolina-Silva Gabriel , Teixeira Mauro M , Pinho Vanessa , Costa Vivian V
Published: February 2025

Exacerbated inflammation is a major contributor to tissue damage and mortality in infectious diseases, including SARS-CoV-2. The resolution phase of inflammation is critical for restoring tissue homeostasis following an injury. Annexin A1 (AnxA1) is a ubiquitous protein that plays a fundamental role in the resolution of inflammation, including in preclinical models of infectious disease. Here, we investigated the role of AnxA1 in coronavirus infection and its potential as a host-targeted therapeutic strategy against SARS-CoV-2. Wild-type (WT) and AnxA1 knockout (AnxA1KO) mice were intranasally infected with the murine betacoronavirus MHV-3 to study the endogenous role of AnxA1. Immunohistochemistry and Western blot analyses in the lungs of MHV-3-infected mice revealed increased AnxA1 expression and its cleavage, which was associated with neutrophilic infiltration (Ly6G+ cells) mainly in peribronchiolar and perivascular regions. AnxA1-deficient mice exhibited higher neutrophilic infiltration and lung damage, alongside increased CXCL1 production in the lungs, when compared to WT-infected mice. In a murine model of SARS-CoV-2 infection in K18-hACE2 mice, we found increased AnxA1 cleavage associated with lung inflammation. Treatment of SARS-CoV-2-infected K18-hACE2 mice with the AnxA1-mimetic peptide, Ac2-26, reduced lung damage and lethality, without altering the host ability to deal with viral replication. Notably, Ac2-26-treated mice exhibited similar levels of protection to that afforded by the nucleotide analogue Remdesivir, following SARS-CoV-2 infection. Our findings highlight the protective role of the endogenous AnxA1 in mitigating coronavirus-induced lung inflammation and underscore the therapeutic potential of AnxA1 mimetic Ac2-26as a host-targeted therapy against SARS-CoV-2.
Inspecting Consistency Between US and European Vitamin D Guidelines Using Physiologically-Based Pharmacokinetics Modelling
Authors: Tao You
Published: February 2025

According to the US official guideline for vitamin D, serum 25-hydroxyvitamin D over 125 nmol/L is linked to potential toxicity. Using a physiologically-based pharmacokinetics model based on a randomised controlled trial in Cape Town, South Africa, we showed the 2000 IU daily dose, recommended by European Food Safety Agency as a safe dose, is expected to lead to serum concentration exceeding the 125 nmol/L threshold among some children and adolescents. This highlights inconsistency between different guidelines and the need to use modelling to bridge the gap between dose and pharmacokinetics.