bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Disease and Future Perceptions of Financial Control
Authors: Davis Victoria H. , Zhang Guanghao , Patel Minal R.
Published: February 2025

Objective:

Rising health care costs and chronic disease prevalence have increased concerns about health-related financial burden. This study examined how baseline chronic disease burden was associated with subsequent perceptions of financial control ∼9 years later.

Methods:

Data came from the Midlife in the United States (MIDUS) cohort, with MIDUS 1 and 2 used as baseline predictors for future perceived financial control outcomes at MIDUS 3. Adjusted mixed effect models examined the relationship between baseline chronic disease burden on 4 variables representing future perceptions of financial control.

Results:

A total of 3297 participants [mean (SD) age: 54 (11.36) y] were included. Greater chronic disease burden and medication use at baseline were associated with a higher likelihood of inadequate resources [adjusted odds ratio (AOR) = 1.22; 95% CI: 1.07–1.38; P = 0.001 and AOR = 1.29; 95% CI: 1.13–1.46; P = 0.001, respectively]. Having more chronic conditions predicted reduced feelings of financial control (AOR=0.85; 95% CI, 0.78-0.93; P<0.001) and a more pessimistic financial outlook (AOR = 0.87; 95% CI: 0.79–0.97; P < 0.01). Higher baseline cholesterol levels showed mixed associations: better perception of current finances (AOR = 1.36; 95% CI: 1.22–1.51; P=0.001) but reduced sense of financial control (AOR = 0.86; 95% CI: 0.78–0.95; P < 0.001) and more negative financial outlook (AOR = 0.69; 95% CI: 0.62–0.77; P < 0.001). No baseline factors predicted bill payment capability.

Conclusion:

The findings suggest a need for additional strategies to reduce the financial burden of chronic diseases.
Intolerance of Uncertainty and Its Association With Cancer-Related Symptoms
Authors: Yang Yesol , Lin Yufen , Kim Bohyun , Gorka Stephanie M. , Von Ah Diane
Published: February 2025

Background

Cancer-related symptoms have negative impacts on the health outcomes of adults with cancer. Thus, it is critical to identify who might be at risk. Intolerance of uncertainty (IU) could be the major contributor for cancer-related symptoms; however, this relationship is understudied in the context of cancer.

Objective

The purpose of this scoping review was to map the literature that has investigated IU and its link to cancer-related symptoms.

Methods

This scoping review used the framework proposed by Arksey and O’Malley and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). A comprehensive search was conducted using 5 databases. English-language primary research published focusing on IU and cancer-related symptoms was included in this review.

Results

Of 12 articles included in this review, 11 studies found a positive relationship of IU with affective symptoms, including anxiety, depression, stress, fear, worry, and distress. Additionally, one study showed that higher IU was associated with greater cognitive impairment and that association was mediated by anxiety.

Conclusion

Findings from this scoping review support the positive association between IU and cancer-related symptoms. This review further suggests that IU could be a potential risk factor for cancer-related affective and cognitive symptoms.

Implication for Practice

The incidence of affective and cognitive symptoms in cancer survivors is high. Given that IU is associated with these symptoms, IU-focused treatments may be beneficial in this group.
Robotic-Assisted Minimally Invasive Transforaminal Lumbar Interbody Fusion
Authors: Martinez Orlando , Shah Varunil , Herring Eric Z. , Labak Collin M. , Mauria Rohit , Smith Gabriel A.
Published: February 2025

Instrumentation of the spine has a long history with the advent and eventual evolution of a number of devices, specifically the pedicle screw which is the primary method of instrumenting the thoracolumbar spine. Traditionally, these were placed using anatomical landmarks; however, as technology has advanced, we have seen the integration of fluoroscopy, navigation, and now robotics for assistance. The integration of robotics into spine surgery has led to increased research and industry investment, which continues to push this promising new technology forward. This paper provides an overview of the robotic arm’s effects on surgical outcomes, explores the revolutionary technology behind its remarkable performance, and describes its use in minimally invasive transforaminal lumbar interbody fusion which maximizes efficiency.
The Impact of National Orthopaedic Fracture Registries: A Systematic Review
Authors: Jozefowski Nicolas , Eikani Carlo , Lingampalli Nithya , Lawler Patrick , Barrett Athena , Hoyt Aaron , Pickles Andrew , Huggins Elizabeth , Agel Julie , Seymour Rachel , Nguyen Mai , Marmor Meir , Levack Ashley E. ,   the OTA Classification and Outcomes Committee
Published: February 2025

Purpose:

Large-scale registry data efforts are common in orthopaedic surgery; however, there is wide variation between registries and little known about registry impact. The purpose of this study was to assess the publication or “scholarly” impact of current national trauma/fracture registries.

Methods:

A search was executed to identify potential national and international trauma/fracture registries and create a comprehensive list of registries. Thirty-four relevant national registries were identified. Searches were executed to identify any published articles published by or affiliated with the selected registries. Over 13,000 abstracts were screened by at least 2 reviewers. The full text of 650 articles were screened by at least 2 reviewers, and data were extracted from 383 articles. Citations were excluded if they were reviews and meta-analyses; referencing non–trauma-specific, insurance, institutional, or state-wide databases; describing facial, spine, or rib trauma; reporting nonregistry data; and did not report on fracture patients. Data were collected at the article level and registry level.

Results:

The median number of articles per registry was 3.5 (range: 1–66) with a median impact factor of 3.2 (range per registry: 1.4–11.0). The National Hip Fracture Database (United Kingdom) had the highest publication rate per year of any registry (3.9). Twenty-four percent of registries had a publication rate of greater than 1 article per year, whereas only 8.8% had a publication rate over 2 per year. Only 8 registries had 10 or more publications in total. The National Trauma Data Bank (United States) had the highest number of fracture-specific publications overall (66) and an average citation rate of 29 per publication. The National Hip Fracture Database had the second highest number of article (62) with an average citation per article of 23.6.

Conclusion:

With the exception of a few registries, most national trauma/fracture registries have low yearly publication and citation rates. Researchers must consider the utility of resources needed to sustain registry efforts in the context of the impact of registry data. Future studies will seek to identify salient features of the highest impact registries.
Case study on the applicability of the international classification of functioning, disability, and health in a patient with mitochondrial myopathy treated in the rehabilitation service
Authors: Taranu Mihaela , Borda Daniel , Rivadeneira Jorge , Laxe Sara
Published: February 2025

Background:

Mitochondrial myopathies are rare neuromuscular diseases characterized by heterogeneous symptoms and severity. They affect multiple organs, including the brain, peripheral nervous system, muscles, kidneys, and liver.

Objective:

To illustrate how the application of the International Classification of Functioning, Disability, and Health (ICF) can help in managing a patient with mitochondrial myopathy in a rehabilitation setting.

Methods:

We present the case of a 26-year-old male diagnosed with a neuromuscular disease at age 12, exhibiting bilateral eyelid ptosis, dysphonia, dysphagia, and motor disorders. The patient underwent a thorough physical evaluation and various scales. The ICF model was employed to document and quantify deficits using a standardized template and numerical qualifiers.

Results:

Priority treatment areas included reeducation of postural and gait patterns, improving aerobic capacity through physical therapy, and managing pain via myofascial infiltration. Post-treatment, significant improvements were observed, although persistent challenges in participation domains, such as mobility in urban environments and employment, remained.

Conclusions:

This case study highlights the utility of the ICF framework in structuring rehabilitation plans, setting clear objectives, and evaluating outcomes for patients with rare diseases like mitochondrial myopathy. The ICF facilitates standardized assessment and comparison across different pathologies, promoting an integrative biopsychosocial model in rehabilitation.
FDG PET/CT in 2 Cases of Primary Urothelial Carcinoma of the Prostate
Authors: Man Xiaojun , Song Xiandong , Dong Aisheng
Published: February 2025

Primary prostatic urothelial carcinoma is a very rare aggressive tumor with poor prognosis. We describe FDG PET/CT findings in 2 patients with primary prostatic urothelial carcinoma. In 1 patient, FDG PET/CT showed intense activity of the prostate tumor with extraprostatic invasion. In the other patient, FDG PET/CT showed heterogeneous intense activity of the primary tumor and multiple hypermetabolic metastases in the regional lymph nodes, bone, and lung. Both patients had normal serum total prostate-specific antigen levels. These cases highlight the usefulness of FDG PET/CT in detecting and staging of primary prostatic urothelial carcinoma due to high FDG avidity.
Impact of a Quantitative Early Activity Program on Gastrointestinal Function Following Laparoscopic Pancreaticoduodenectomy: A Single-Center Retrospective Analysis
Authors: Zhang Ling , Zhang Fan , Xiao Chen-Jie , Shu Yue-Fen , Li Zheng , Wang Jun , Tang Wen-Jie
Published: February 2025

Objective:

The objective of this study is to assess the impact of a quantitative early activity program, integrated into the Enhanced Recovery After Surgery (ERAS) protocol on gastrointestinal function in patients undergoing laparoscopic pancreatoduodenectomy (LPD).

Methods:

Perioperative data from 203 patients who underwent LPD at the Department of Comprehensive Treatment of Pancreatic Cancer, Fudan University Shanghai Cancer Center, between January 2021 and December 2022 were analyzed retrospectively. The patients were categorized into 2 groups based on their nursing plans. Group A received the standard perioperative ERAS nursing plan, while group B followed the ERAS plan supplemented with a quantitative early activity program. We assessed postoperative outcomes including bowel sound recovery time, time to first anal exhaust, time to first mobilization, activity compliance 1-week postsurgery, and incidence of postoperative breakthrough pain.

Result:

We compared several postoperative metrics between group A and group B. Specifically, the time to bowel sound recovery was 62.39±17.89 hours in group A versus 56.45±22.85 hours in group B. The time to first anal exhaust was 78.88±71.99 hours in group A compared with 63.62±24.73 hours in group B. The time to first mobilization was 56.98±18.66 hours in group A versus 49.85±20.48 hours in group B. In addition, activity compliance 1-week postsurgery and the incidence of postoperative breakthrough pain (1.55±2.01 times in group A vs. 0.94±1.16 times in group B) were also compared. All these differences were statistically significant (P<0.05). Conversely, the incidence of postoperative complications and the length of hospital stay (11.20±5.69 d in group A vs. 12.47±6.67 d in group B) did not reveal any significant differences (P>0.05).

Conclusion:

The quantitative early activity program for LPD, based on the ERAS protocol, enhances the adherence to postoperative activity and decreases the incidence of breakthrough pain, thereby facilitating gastrointestinal function recovery in patients. This approach merits clinical adoption.
Promoting international acceptance of clinical studies about traditional Chinese medicine interventions
Authors: Li Ling , Luo Xiaochao , Liu Jiali , Yao Minghong , Liu Yanmei , Ma Yu , Huang Luqi , Sun Xin
Published: February 2025

Promoting the international acceptance of clinical studies about traditional Chinese medicine (TCM) interventions is a key strategy for internationalization of TCM. However, the complexities of TCM interventions—in terms of the theories, practice patterns, and components—pose challenges to the design and implementation of clinical studies that are well accepted by the international community. This article summarized the current status of clinical studies about TCM interventions that were published in international journals, explored underlying barriers hindering the international acceptance, and discussed potential strategies for future development.
The effect of the proportion of low-titer O whole blood for resuscitation in pediatric trauma patients on 6-, 12- and 24-hour survival
Authors: Petersen Ethan M. , Fisher Andrew D. , April Michael D. , Yazer Mark H. , Braverman Maxwell A. , Borgman Matthew A. , Schauer Steven G.
Published: February 2025

INTRODUCTION

Hemorrhage is a leading cause of death in pediatric patients. Accumulating data suggest that low-titer group O whole blood (LTOWB) improves clinical outcomes in the pediatric population. We examined what ratio of LTOWB to total blood product conferred a survival benefit in transfused pediatric trauma patients.

METHODS

We retrospectively examined a cohort of injured subjects younger than 18 years from the Trauma Quality Improvement Program database who received any quantity of LTOWB and no documented prehospital cardiac arrest. We created a variable representing the volume of transfused LTOWB divided by the total volume of all transfused blood products administered within the first 4 hours of admission, that is, the proportion of LTOWB transfused. We analyzed increasing proportions of transfused LTOWB to determine whether there was an inflection point conferring increased survival.

RESULTS

From 2020 to 2022, 1,122 subjects were included in the analysis. The median (interquartile range) age was 16 (14–17) years. Firearms were the most common mechanism at 47% followed by collisions at 44%. The median composite injury severity score was 25 (16–34). Survival was 91% at 6 hours, 89% at 12 hours, and 88% at 24 hours. We noted an inflection point with improved survival at an LTOWB proportion of ≥30% of total volume of blood products received. The odds of survival at 6, 12, and 24 hours for those receiving ≥30% LTOWB was 1.85 (1.02–3.38), 2.09 (1.20–3.36), and 1.80 (1.06–3.08), and 3.55 (1.66–7.58), 3.71 (1.89–7.27), and 2.69 (1.44–5.02) when excluding those who died within 1 hour, respectively.

CONCLUSION

Among LTOWB recipients, we found that a strategy of using LTOWB comprising at least 30% of the total transfusion volume within the first 4 hours was associated with improved survival at 6, 12, and 24 hours.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Improvement in Quality of Seizures in Electroconvulsive Therapy With Zotepine
Authors: Matsuoka Teruyuki , Ayani Nobutaka , Yamano Sumihiro
Published: February 2025

Regular symmetric high-amplitude seizure waves, postictal suppression, constant seizure duration, and sympathetic nervous system excitation are used to evaluate the efficacy of electroconvulsive therapy (ECT) for seizures. Seizure quality is rated from 0 to 3 (higher scores indicate better quality) using seizure quality categories (SQC). We report a case in which zotepine (ZTP) improved seizure quality. A woman in her 50s developed schizophrenia in 1993. In December 2021, her delusions, anxiety, and agitation worsened, and she was admitted to our hospital. ECT was started in November 2022 but discontinued after 10 sessions because of the patient's refusal. However, her agitation became more noticeable, and she was placed in isolation in December 2022. ECT was resumed in March 2023 and accompanied by risperidone (RIS) 4 mg, with SQC scores of 1–2 points for sessions 1–8. A gradual change from RIS to ZTP began at session 9, and RIS was discontinued by session 17. The SQC was 2 points with ZTP dose of 150 mg. The SQC improved to 3 points during sessions 21–23 after ZTP dose was increased to 300 mg. The electroencephalogram showed improvement, especially in regular symmetric high-amplitude seizure waves and postictal suppression during sessions 21–23. ECT was terminated in September 2023 (after 27 sessions in total) when the patient was mentally ready to be released from isolation. This case indicates that ZTP may improve the quality of ECT-induced seizures.
Presentation and Types of Childhood Cancer at the Muhimbili National Hospital (MNH), 2023
Authors: Ali Salih Arga Malaz Adam , Laiti Rehema H. , Abd El Raheem Ghada Omer Hamad , Hammor Yasar
Published: February 2025

BACKGROUND

In sub-Saharan Africa in Tanzania, with an incidence of 1.4/100,000 cases. A lot of cancer cases in Tanzania are not diagnosed until later because there aren’t many healthcare institutions offering cancer-related care and treatment. Cancer that manifests in its late stages not only reduces survival chances but also places a heavy load on the healthcare system. a lower-middle-income nation, has numerous barriers to receiving treatment for children’s malignancies. The research aims to study the clinical presentation and types of childhood cancer at the Muhimbili National Hospital.

METHODS

A hospital-based cross-sectional survey and convenience sample technique were used to assess the presentation and association factors of childhood cancer. Descriptive statistics and statistical analysis to assess associations among variables were performed through chi2 and one-way ANOVA. A p-value of <0.05 was considered significant.

RESULTS

141 patients were assessed; the most common types of cancer were Blastoma and Leukaemia between 1 and 5 years. The Sukuma tribe had the highest percentage of patients. Most of the patients came from Dar es Salaam. The majority of patients presented with masses and abdominal distention. There was a statistically significant difference between family history and the type of cancer, between the stage of disease and response to treatment, and between the ages across types of cancer. There is no statistical difference or association between the type of cancer and the history of chronic illness or exposure.

CONCLUSION

Childhood cancer has high mortality and morbidity in Tanzania. Most of the patients die before 5 years old, and patients come to the hospital with a late-stage disease with serious symptoms. Other patients didn’t complete treatment, which may be due to financial problems or a low level of education among carers.
Tremor asymmetry and the development of bilateral phase-specific deep brain stimulation for postural tremor
Authors: He Shenghong , Deli Alceste , West Timothy O , Plazas Fernando R , Pogosyan Alek , Wiest Christoph , Wehmeyer Laura , Baig Fahd , Morgante Francesca , Andrade Pablo , Hart Michael G , FitzGerald James J. , Visser-Vandewalle Veerle , Pereira Erlick A , Green Alexander L , Tan Huiling , Cagnan Hayriye
Published: February 2025

Background

Tremor phase-locked deep brain stimulation (DBS) has been shown to modulate symptom severity in patients with postural tremor, including essential (ET) and dystonic tremor (DT). This, provides a potential alternative therapy that targets the underlying pathological oscillations with less energy delivered to the brain than existing systems. Previous phase-locked DBS studies focused on evaluating the effect of unilateral stimulation on the tremor-dominant hand. Considering that postural tremor usually presents bilaterally, it remains unknown how tremor asymmetry interacts with stimulation in the context of bilateral phase-locked DBS, which was investigated in the current study.

Methods

Archival limb acceleration from nine ET patients with postural tremor was analysed to explore potential asymmetries in tremor amplitude, frequency, and instability across the two upper limbs, and the relationship between these asymmetries and continuous high-frequency DBS (cDBS). Then, as a proof of concept, bilateral phase-locked DBS was tested in one ET and one DT patient with postural tremor and chronically implanted DBS devices.

Results

Our results confirmed that postural tremor is asymmetric; larger tremor power being associated with smaller amplitude and frequency stability in one hand compared to the other. These asymmetries were significantly reduced during cDBS. The effects of cDBS on aforementioned characteristics were greater on the tremor with larger amplitude. Accordingly, the effects of bilateral phasic DBS were also asymmetric.

Conclusions

This study creates a better understanding of tremor asymmetry and its relationship with DBS and provides important insights for the development of patient specific approaches for tremor.
A maize near-isogenic line population designed for gene discovery and characterization of allelic effects
Authors: Zhong Tao , Mullens Alex , Morales Laura , Swarts Kelly L , Stafstrom William C , He Yijian , Sermons Shannon M , Yang Qin , Lopez-Zuniga Luis O , Rucker Elizabeth , Thomason Wade E , Nelson Rebecca J , Jamann Tiffany , Balint-Kurti Peter J , Holland James B
Published: February 2025

In this study we characterized a panel of 1,264 maize near-isogenic lines (NILs), developed from crosses between 18 diverse inbred lines and the recurrent parent B73, referred to as nested NILs (nNILs). 884 of the nNILs were genotyped using genotyping-by-sequencing (GBS). Subsequently, 24 of these nNILs, and all the parental lines, were re-genotyped using a high-density SNP chip. A novel pipeline for calling introgressions, which does not rely on knowing the donor parent of each nNIL, was developed based on a hidden Markov model (HMM) algorithm. By comparing the introgressions detected using GBS data with those identified using chip data, we optimized the HMM parameters for analyzing the entire nNIL population. A total of 2,972 introgressions were identified across the 884 nNILs. Individual introgression blocks ranged from 21 bp to 204 Mbp, with an average size of 17 Mbp. By comparing SNP genotypes within introgressed segments to the known genotypes of the donor lines we determined that in about one third of the lines, the identity of the donors did not match expectation based on their pedigrees.

We characterized the entire nNIL population for three foliar diseases. Using these data, we mapped a number of quantitative trait loci (QTL) for disease resistance in the nNIL population and observed extensive variation in effects among the alleles from different donor parents at most QTL identified. This population will be of significant utility for dissecting complex agronomic traits and allelic series in maize.

Significance Statement

The study reports the characterization of a publicly available population of 1,264 maize near-isogenic lines largely derived from a single recurrent parent and 18 donor lines. This population is likely to be of significant utility for the characterization of allelic series at loci of interest.
Microbial metabolite 4-ethylphenylsulfate (4EPS) interacts with AT1R, reduces blood pressure and outcome of AngII-induced aortic aneurysm
Authors: Harford Terri J. , Singh Dhanachandra Khuraijam , Pardhi Triveni R. , Desnoyer Russell , Ravi Tarun , Jara Zaira Palomino , Zalavadia Ajay , Stenson Kate , Prasad Sathyamangla V Naga , Karnik Sadashiva S.
Published: February 2025

BACKGROUND

Plasma accumulation of the gut microbial metabolite, 4-ethylphenylsulfate (4EPS), produced from dietary protein aromatic amino acids has been observed in correlative and associative studies of cardiovascular, renal, metabolic and neurological diseases. 4EPS level increases upon AngII infusion in mice. How 4EPS alters host physiology to contribute to progression of any disease state is currently unknown.

METHODS

To test the hypothesis that 4EPS interferes with angiotensin binding to AT1R, we used multiple approaches: AT1R pharmacology, cell-signaling, ex vivo vascular contraction and a mouse model of angiotensin-induced aortic aneurysm (AA) disease. ApoE-null mice were fed high-fat diet and infused with AngII, or co-infused with 4EPS and Olmesartan. BP was recorded. At the end of infusion, aortas were assessed for severity of AA, contractile response and histopathology. To evaluate signaling associated with different AA outcomes plasma proteomics analysis was done.

RESULTS

In vitro, 4EPS reduced the binding of angiotensin and Candesartan to AT1R and calcium signaling. Ex vivo, 4EPS decreased vasomotor response of the aorta to AngII. In vivo, 4EPS inhibited AngII-mediated increase of BP and reduced mortality from AA. Abdominal aorta remodeling in 4EPS+AngII co-infused mice showed an increase of elastin area and reduced thickening of intimal/medial layers. Plasma proteome analysis indicated significant change in actin-cytoskeletal signaling associated with reduced ERK1/2 and Filamin-A activation, and cell motility.

CONCLUSIONS

Benign antagonism of AT1R by 4EPS involves direct interaction with AT1R. Molecular mechanisms of 4EPS responsible for reduced AA associated mortality in mice are distinct from those of AT1R blocker, Olmesartan.

GRAPHIC ABSTRACT
Feeding niches drive specialist herbivore responses of conspecific insects to plant defenses in biocontrol
Authors: Kaur Jasleen , Navia Lucia , Kraus Emily , Menocal Octavio , Hahn Philip G.
Published: February 2025

1. Biological invasions threaten global ecosystems and economies, prompting the need for sustainable management approaches such as releasing natural enemies from the native range (i.e., classical biological control; CBC). While the release of multiple natural enemies can enhance the effectiveness of CBC, interactions between these agents and their host plants defenses are poorly understood. 2. This study explored the interactions between two congeneric specialist herbivores introduced for the control of Dioscorea bulbifera (air potato) in Florida, USA: Lilioceris cheni (Coleoptera: Chrysomelidae), which feeds primarily on leaves and L. egena, which feeds primarily on the aerial reproductive structures (i.e., bulbils). Specifically, we investigated whether foliar herbivory by L. cheni or induced defenses by jasmonic acid (JA) or salicylic acid (SA) influenced L. egena's feeding behavior and performance on bulbils. 3. We conducted feeding assays to measure bulbil consumption and its relationship to pupal mass and adult eclosion as indicators of beetle performance. Additionally, we performed dose-dependent feeding assays to test how varying concentrations of saponins, a key defense compound in air potato, influenced feeding and survival of L. cheni and L. egena. 4. Our results indicated no significant differences in bulbil feeding by L. egena across treatments; however, SA-treated plants produced significantly heavier pupae and adults compared to controls. Dose-response assays revealed non-linear, hump-shaped, feeding and survival patterns in L. cheni, while L. egena experienced reduced feeding and survival with increasing saponin concentrations. 5. These findings suggest that the two beetles respond differently to plant defenses while occupying distinct feeding niches, likely allowing for additive impacts on D. bulbifera. This study provides insights into the role of plant defenses in CBC and informs strategies to optimize biocontrol programs for invasive species management.
Lytic IFNγ is stored in granzyme B-containing cytotoxic granules and co-secreted by effector CD8⁺ T cells
Authors: Li Xuemei , Schirra Claudia , Wirkner Marie-Louise , Tu Szu-Min , Lin Chin-Hsin , Hohmann Meltem , Alawar Nadia , Chouaib Abed , Becherer Ute , Pattu Varsha , Rettig Jens , Krause Elmar , Chang Hsin-Fang
Published: February 2025

Cytotoxic CD8⁺ T cells form immunological synapses with target cells and release effector molecules, including IFNγ, to mediate antitumor immunity. However, the mechanisms by which IFNγ contributes to cytotoxicity remain incompletely understood. Here, we identify a subset of IFNγ stored within GzmB⁺ cytotoxic granules (CGs) in activated mouse and human CD8⁺ T cells, termed ’lytic IFNγ’. Lytic IFNγ is polarized to the synapse and co-secreted with GzmB in both soluble and supramolecular attack particle (SMAP)-associated forms. Mouse CD8⁺ T cells lacking the vesicle priming factor Munc13-4 exhibit impaired both CG and early IFNγ release at the immunological synapse, while prolonged synaptic engagement restores IFNγ secretion. Super-resolution imaging demonstrates that sustained synaptic interactions drive IFNγ secretion at distal membrane sites, suggesting the existence of distinct IFNγ populations with potentially diverse functions beyond lytic IFNγ. These findings uncover an unrecognized mechanism of IFNγ storage and release, underscoring its pivotal role in CD8⁺ T cell-mediated tumor elimination.
Metabolic remodeling of microorganisms by obligate intracellular parasites alters mutualistic community composition
Authors: Bisesi Ave T. , Carlson Ross P. , Cotner Lachlan , Harcombe William R.
Published: February 2025

Bacteria carry many types of obligate intracellular parasites, including plasmids and bacteriophage. During infection, these parasites redirect intracellular resources away from bacterial processes toward parasite production. Because parasite-induced metabolic changes influence host traits such as growth rate, nutrient uptake, and waste excretion, parasitic infection should alter how microbes contribute to important community and ecosystem functions. Yet there are few empirical tests of how infection shapes metabolically-mediated interactions between host and non-host species. Here, we integrated a genome-scale metabolic modeling approach with anin vitroobligate cross-feeding system to investigate the metabolic consequences of two intracellular parasites ofEscherichia coli: the conjugative plasmid F128 and the filamentous phage M13. We examined the impact of these parasites on interactions between bacteria in a multispecies community composed ofE. coli,Salmonella enterica,andMethylobacterium extorquens. Modeling predicted that parasitic infection ofE. colishould have consequences for host growth rate and the secretion and reuptake of carbon byproducts. These theoretical results aligned broadly within vitroexperiments, where we found that parasitic infection changed the excretion profile ofE. coli, inducing the net externalization of lactate. We also found that parasite-driven changes to metabolism increased the density of cross-feeding species and changes to community composition were generalizable across community interactions and some host and parasite genotypes. Our work emphasizes that microbes infected by obligate intracellular parasites have different metabolisms than uninfected cells and demonstrates that these metabolic shifts can have significant consequences for microbial community structure and function.

IMPORTANCE

The intracellular parasites of bacteria shape the structure and function of microbial communities in a variety of ways, including by killing their hosts or transferring genetic material. This study uses a combination of flux balance analysis and anin vitrosystem consisting ofEscherichia coli,Salmonella enterica,Methylobacterium extorquens, and two intracellular parasites ofE. coli, the F128 plasmid and the filamentous phage M13, to investigate how parasites change the community contributions of their hosts via metabolic remodeling. Flux balance analysis suggests that parasites change intracellular demand for different metabolic processes, leading to shifts in the identities and concentrations of compounds that infected hosts externalize into the environment. This finding is supported by experimental results, which additionally show that infection can induce the production of lactate. These findings extend our understanding of how bacteriophage and plasmids shape the structure and function of microbial communities.
Phasing in and out of phytophagy: phylogeny and evolution of the family Eurytomidae (Hymenoptera: Chalcidoidea) based on Ultraconserved Elements
Authors: Zhang Yuanmeng Miles , Delvare Gerard , Blaimer Bonnie B , Cruaud Astrid , Rasplus Jean-Yves , Brady Sean G , Gates Michael W
Published: February 2025

We present the first global molecular phylogenetic hypothesis for the family Eurytomidae, a group of chalcidoid wasps with diverse biology, with a representative sampling (197 ingroups and 11 outgroups) that covers all described subfamilies, and 70% of the known genera. Analyses of 962 Ultra-Conserved Elements (UCEs) with concatenation (IQ-TREE) and multispecies coalescent approaches (ASTRAL) resulted in highly supported topologies in recovering the monophyly of Eurytomidae and its four subfamilies. The taxonomy of Eurytomidae, and in particular the large subfamily Eurytominae, needs major revisions as most large genera are recovered as para- or polyphyletic, and the erection of multiple new genera is required in the future to accommodate these taxa. Here, we synonymize the genera Cathilaria (C. certa, C. globiventris, C. opuntiae, and C. rigidae) and the monotypic Aiolomorphus rhopaloides within Tetramesa syn. nov., Parabruchophagus (P. kazakhstanicus, P. nikolskaji, P. rasnitsyni, P. saxatilis, and P. tauricus) and Exeurytoma (E. anatolica, E. caraganae, and E. kebanensis) within Bruchophagus syn. nov.. We also provide 137 DNA barcode COI fragments extracted from the UCE contigs to aid in future identifications of Eurytomidae using this popular genetic marker. Eurytomidae most likely originated in South America with an estimated crown age of 83.37 Ma. Ancestral state reconstruction indicates that secondary phytophagy has evolved at least seven times within the subfamily Eurytominae, showcasing the evolutionary flexibility of these vastly understudied wasps.
FISHNET: A Network-based Tool for Analyzing Gene-level P-values to Identify Significant Genes Missed by Standard Methods
Authors: Acharya Sandeep , Moghaddam Vaha Akbary , Jung Wooseok J. , Kang Yu S. , Liao Shu , Province Michael A. , Brent Michael R.
Published: February 2025

FISHNET uses prior biological knowledge, represented as gene interaction networks and gene function annotations, to identify genes that do not meet the genome-wide significance threshold but replicate nonetheless. Its input is gene-level P-values from any source, including omicsWAS, aggregation of GWAS P-values, CRISPR screens, or differential expression analysis. It is based on the idea that genes whose P-values are low due to sampling error are distributed randomly across networks and functions, so genes with suggestive P-values that cluster in densely connected subnetworks and share common functions are less likely to reflect sampling error and more likely to replicate. FISHNET combines network and function analysis with permutation-based P-value thresholds to identify a small set of exceptional genes that we call FISHNET genes.

Applied to 11 cardiovascular risk traits, FISHNET identified 19 gene-trait relationships that missed genome-wide significance thresholds but, nonetheless, replicated in an independent cohort. The replication rate of FISHNET genes matched or exceeded that of other genes with similar P-values. FISHNET identified a novel association betweenRUNX1expression and HDL that is supported by experimental evidence thatRUNX1promotes white fat browning, which increases HDL cholesterol levels. FISHNET also identified an association betweenLTBexpression and BMI that is supported by experimental evidence that higher LTB expression increases BMI via activation of the LTβR pathway. Both associations failed genome-wide significance thresholds, highlighting FISHNET’s ability to uncover meaningful relationships missed by traditional methods. FISHNET software is freely available athttps://doi.org/10.5281/zenodo.14765850.
Rhizosphere Bacteria and Fungi are Differentially Structured by Host Plants, Soil Mineralogy and Ectomycorrhizal Communities in the Alaskan Tundra
Authors: Schaefer Sean Robert , Montaño-López Fernando , Holland-Moritz Hannah , Hicks Pries Caitlin , Ernakovich Jessica Gilman
Published: February 2025

The rhizosphere contains a diverse group of bacteria and fungi living near plant roots whose composition and function are key drivers of ecosystem and biogeochemical processes. Despite rich literature on rhizosphere communities, surprisingly few studies have examined the drivers of rhizosphere community structures in natural settings. We collected 513 root samples from 141 individual plants representing six plant species and three mycorrhizal association types across four glacial drifts in the North Slope of Alaska. Glacial drifts ranged from 11,000 to 4.5 million years since deglaciation representing a gradient in glacial history and mineralogical weathering. We found that glacial history, a strong proxy for soil mineralogy, explained most of the captured variation in rhizosphere bacterial communities (13.3%) and ectomycorrhizal fungal communities (10.2%) while interactions between glacial history and host plants explained the most variation in fungal rhizosphere communities (11.6%). We analyzed ectomycorrhizal fungal communities from the shrubBetula nanaacross spatial scales and sites and found a large correlation between ectomycorrhizal and rhizosphere communities, and that ectomycorrhizal composition was most similar among root fragments belonging to the same plant, followed by plants at the same site, and were most dissimilar for plants at different sites.
TSC1mRNA processing alterations in tuberous sclerosis complex (TSC) patients with negative or inconclusive genetic testing results
Authors: de Mello Garcia Arthur Bandeira , da Silveira Fischer Taís , de Freitas Pinho Maria Clara , Jataí Lucas Fernandesw , da Silva Patrícia Santos , Andreis Tiago Finger , Reis Larissa Brussa , Oliveira Netto Cristina Brinckmann , Ashton-Prolla Patricia , Rosset Clévia
Published: February 2025

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by the presence of pathogenic germline variants inTSC1orTSC2genes. However, mostTSC1andTSC2genetic testing strategies are limited and about 20% of patients have inconclusive or negative results. In this study, we standardized a low-cost technique based on RT-PCR followed by Sanger sequencing, aimed to complement genetic testing strategies. Patients with clinical suspicion of TSC andTSC1andTSC2inconclusive (n=3) or negative (n=1) genetic testing results were recruited. Exon 5 skipping inTSC1gene was identified in one patient with a previous negative genetic testing result. In addition, a 9-base-pair intronic inclusion was found in theTSC1of an individual with a previously identified variant of uncertain significance, c.664-10A>C. No alterations were found in the other two patients. The present study was successful in identifying errors in mRNA processing in two TSC patients with previously negative or inconclusive genetic testing results. Furthermore, this strategy was useful to reclassify a VUS to pathogenic. Finally, the validated technique could be used to complement coding region genetic tests and to investigate causality of VUS in TSC and other monogenic diseases.

Highlights

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A novel cDNA analysis method revealed the presence of exon 5 skipping in the

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TSC1gene

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A nine-base-pair retention in TSC1 mRNA is caused by the intronic variant c.664-10A>C

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The variant of uncertain significance c.664-10A>C inTSC1was reclassified as pathogenic

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A strategy using cDNA could be a good complement to conventional molecular diagnosis protocols
Association of ICH Score with Withdrawal of Life-Sustaining Treatment: A Decade from the Florida Stroke Registry
Authors: Massad Nina , Zhou Lili , Manolovitz Brian , Asdaghi Negar , Gardener Hannah , Ying Hao , Gutierrez Carolina M , Jameson Angus , Rose David , Kottapally Mohan , Merenda Amedeo , O’Phelan Kristine , Koch Sebastian , Romano Jose G. , Rundek Tatjana , Alkhachroum Ayham
Published: February 2025

Background and Purpose

The intracerebral hemorrhage (ICH) score was created as a tool improve communication and consistency among providers, and authors initially cautioned against its use as a predictor of outcomes. We aimed to investigate the association of ICH score with mortality and withdrawal of life-sustaining treatment (WLST).

Methods

Patients with a diagnosis of ICH were identified using data from Florida Stroke Registry (FSR) hospitals participating in the American Heart Association (AHA) Get with the Guidelines-Stroke (GWTG-S) from 2013-2022. Outcomes of WLST and in-hospital mortality were collected. ICH score was stratified into three groups: ICH score 0-2; 3-4; 5-6. Importance plots were generated to identify the most predictive factors associated with WLST. AUC-ROC curves were generated for logistic regression (LR) and random forest (RF) models, adjusted for relevant confounders. Secondary outcome analyses were performed using stratified univariate logistic regression to assess changes between 2015-2018 and 2019-2022.

Results

A total of 12,426 (26%) patients had documented ICH scores (mean age 69, 55% male, 56% white). The most predictive factors associated with WLST were ICH score, age, state region, presenting level of consciousness, insurance status and race (RF AUC=.94, LR AUC=.82). Mortality was 6.6%, 41.5% and 66% for ICH score 0-2, 3-4 and 5-6. Decision to WLST occurred more for ICH scores 3-4 (OR 9.35, 95% CI: 8.5-10.3) and ICH scores 5-6 (15.43, 95% CI: 15.28-22.74). Early WLST (< 2 days) was more likely for ICH score 3-4 (OR 2.97, 95% CI: 2.48-3.55) and score 5-6 groups (OR 9.51, 95% CI: 7.33-12.35).

Conclusion

Among ICH patients admitted across Florida, we noted a significant association between ICH score and likelihood of mortality, decision to WLST, and specifically WLST within two days of presentation. We identified the most predictive variable associated with WLST to be the ICH score. These findings suggest a continued influence of the self-fulfilling prophecy in ICH.
Repurposing Regulatory Toxicology Safety Data to Identify Potential Pro-Longevity Substances
Authors: Miwa Satomi , Kucheryavenko Olena , Herrmann Kristin , Saunter Christopher , Raimundo Adelaide , Weinkove David , Niemann Lars , von Zglinicki Thomas
Published: February 2025

The repurposing of existing biosafety datasets offers unique opportunities in biomedical research. Here, we demonstrate how pesticide toxicity data, which include long-term survival studies in mammalian models, can be harnessed to uncover potential drug candidates or drug targets that can improve survival. We show that these substances frequently affect mitochondrial bioenergetics and that they can improve animal healthspan.
Cardiac diffusion kurtosis imaging in the human heart in vivo using 300mT/m gradients
Authors: Afzali Maryam , Coveney Sam , Mueller Lars , Jones Sarah , Fasano Fabrizio , Evans C John , Teh Irvin , Dall’Armellina Erica , Szczepankiewicz Filip , Jones Derek K , Schneider Jürgen E
Published: February 2025

Purpose

Diffusion tensor imaging (DTI) is commonly used in cardiac diffusion magnetic resonance imaging (dMRI). However, the tissue’s microstructure (cells, membranes, etc.) restricts the movement of the water molecules, making the spin displacements deviate from Gaussian behaviour. This effect may be observed with diffusion kurtosis imaging (DKI) using sufficiently high b-values (b>450 s/mm2), which are presently outside the realm of routine cardiac dMRI due to the limited gradient strength of clinical scanners. The Connectom scanner with Gmax= 300 mT/m enables high b-values at echo times (TE) similar to DTI on standard clinical scanners, therefore facilitating cardiac DKI in humans.

Methods

Cardiac-gated, second-order motion-compensated dMRI was performed with bmax= 1350 s/mm2in 10 healthy volunteers on a 3T MRI scanner with Gmax= 300 mT/m. The signal was fitted to a cumulant expansion up to and including the kurtosis term and diffusion metrics such as fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) were calculated.

Results

We demonstrate deviation of the signal from monoexponential decay for b-values>450 s/mm2(MK = 0.32±0.03). Radial kurtosis (RK = 0.35±0.04) was observed slightly larger than axial kurtosis (AK = 0.27±0.02), and the difference is statistically significant (RK−AK = 0.08±0.04, p = 2e−4).

Conclusion

This work demonstrates the feasibility of quantifying kurtosis effect in the human heart in vivo (at an echo time shorter than typical TEs reported for cardiac DTI), using high-performance gradient systems (which are 4-8 times stronger than on standard clinical scanners). Our work lays the foundation for exploring new biomarkers in cardiac dMRI beyond DTI.
Arabidopsisseed stored mRNAs and translation regulation during post-harvest ripening and imbibition
Authors: Balarynová J. , Klčová B. , Čegan R. , Raabe K. , Krejčí P. , Bednář P. , Potěšil D. , Pustka V. , Tarkowská D. , Turečková V. , Zdráhal Z. , Honys D. , Smýkal P.
Published: February 2025

Seed germination marks the critical transition from dormancy to active growth, driven by environmental cues and water availability. This study explores translational regulation during germination by comparing twoArabidopsis thalianaaccessions with contrasting dormancy phenotypes: Columbia (Col), which germinates readily, and Cape Verde Islands (Cvi), which exhibits deep dormancy. Using sucrose gradient centrifugation, we isolated monosomal and polysomal fractions from freshly harvested (FH), after-ripened (AR), and imbibed (IM) seeds. RNA-seq analysis revealed stage- and genotype-specific gene expression, with Col IM seeds displaying the highest number of expressed genes. We identified ∼14,000 mRNAs in FH seeds, increasing to 19,000 in Col and 17,000 in Cvi upon imbibition. Of these, 9,000 were shared, while 3,000 were accession-specific in monosomes. Enrichment analysis highlighted molecular pathways associated with translation and dormancy release. Analysis of RNA modifications identified N1-methyladenosine (m1A) as the predominant modification, with Col seeds exhibiting higher m1A levels than Cvi, peaking at three months post-harvest. m6A sequencing revealed distinct modification patterns between accessions, with the highest abundance of m6A-modified transcripts in IM seeds. Positional analysis of m6A peaks suggested a link to differential gene expression between Col and Cvi. Proteomic analysis identified ∼15,000 proteins, with translation-related proteins enriched in IM seeds. Notable differences between Col and Cvi were observed in both monosomal and polysomal fractions. RNA-binding proteins exhibited similar profiles in FH and AR stages but diverged significantly in IM seeds. Col-specific proteins were enriched in 40S ribosomes, processing bodies, and RNA-binding complexes.

These findings provide new insights into the molecular and translational dynamics underlying seed germination, advancing our understanding of dormancy release and early seedling establishment.