bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acetalax and Bisacodyl for the Treatment of Triple-Negative Breast Cancer: A Combined Molecular and Preclinical Study
Authors: Reinhold William C. , Marangoni Elisabetta , Elloumi Fathi , Montagne Remi , Varma Sudhir , Wang Yanghsin , Rezai Keyvan , Morriset Ludivine , Dahmani Ahmed , El Botty Rania , Huguet Léa , Mizunuma Makito , Takebe Naoko , Huguet Samuel , Luna Augustin , Pommier Yves 
Published: February 2025

Abstract
The recalcitrant nature of triple-negative breast cancer (TNBC) calls for novel treatments. Acetalax (oxyphenisatin acetate) and bisacodyl, which have been and are extensively used orally as laxatives, have recently been reported to exhibit selective antiproliferative activity when incubated with cancer cells and xenograft models. Here, we show that they are both preferentially active in TNBC cell lines, and that their activity patterns overlap across the 1,000 cell lines of the Sanger database but are unique and distinct from the standard chemotherapies. Multivariate transcriptomic analyses demonstrate that expression of the ion transporter TRPM4 and two other cell surface genes predict the activity of both drugs. In vivo testing shows that both Acetalax and bisacodyl induce complete regression of different TNBC patient-derived xenografts. Acetalax pharmacokinetics shows a 5.8-hour terminal half-life and drug penetration in TNBC tumors and brain.

Significance:
Acetalax and bisacodyl represent a prospective novel drug mechanism-of-action type, affect mitochondrial function and affect tumor growth in vivo. Their activity may be predicted by TRPM4 but with more accuracy adding other genes in multivariate analysis for triple negative breast cancer (TNBC). Acetalax has a biphasic mean half-life of 5.8 hours.
Novel Therapeutic Approach Targeting CXCR3 to Treat Immunotherapy Myocarditis
Authors: Huang Yuhsin Vivian , Sun Yin , Chou Harrison , Wagner Noah , Vitale Maria Rosaria , Bayer Abraham L. , Xu Bruce , Lee Daniel , Lin Zachary , Branche Corynn , Waliany Sarah , Neal Joel W. , Wakelee Heather A. , Witteles Ronald M. , Nguyen Patricia K. , Graves Edward E. , Berry Gerald J. , Alcaide Pilar , Wu Sean M. , Zhu Han 
Published: February 2025

BACKGROUND:
Immune checkpoint inhibitors (ICIs) are successful in treating many cancers but may cause immune-related adverse events. ICI-mediated myocarditis has a high fatality rate with severe cardiovascular consequences. Targeted therapies for ICI myocarditis are currently limited.

METHODS:

We used a genetic mouse model of PD1 deletion (
MRL/Pdcd1

−/−

) along with a novel drug-treated ICI myocarditis mouse model to recapitulate the disease phenotype. We performed single-cell RNA-sequencing, single-cell T-cell receptor sequencing, and cellular indexing of transcriptomes and epitopes on immune cells isolated from
MRL
and
MRL/Pdcd1

−/−

mice at serial time points. We assessed the impact of macrophage deletion in
MRL/Pdcd1

−/−

mice, then inhibited CXCR3 (C-X-C motif chemokine receptor 3) in ICI-treated mice to assess the therapeutic effect on myocarditis phenotype. Furthermore, we delineated the functional and mechanistic effects of CXCR3 blockade on T-cell and macrophage interactions. We then correlated the results in human single-cell multiomics data from blood and heart biopsy data from patients with ICI myocarditis.

RESULTS:

Single-cell multiomics demonstrated expansion of CXCL (C-X-C motif chemokine ligand) 9/10+CCR2+ macrophages and CXCR3hi (C-X-C motif chemokine receptor 3 high-expressing) CD8+ (cluster of differentiation) effector T lymphocytes in the hearts of
MRL/Pdcd1

−/−

mice correlating with onset of myocarditis development. Both depletion of CXCL9/10+CCR2+ (C-C motif chemokine receptor) macrophages and CXCR3 blockade, respectively, led to decreased CXCR3hi CD8+ T-cell infiltration into the heart and significantly improved survival. Transwell migration assays demonstrated that the selective blockade of CXCR3 and its ligand, CXCL10, reduced CXCR3+CD8+ T-cell migration toward macrophages, implicating this interaction in T-cell cardiotropism toward cardiac macrophages. Furthermore, cardiomyocyte apoptosis was induced by CXCR3hi CD8+ T cells. Cardiac biopsies from patients with confirmed ICI myocarditis demonstrated infiltrating CXCR3+ T cells and CXCL9+/CXCL10+ macrophages. Both mouse cardiac immune cells and patient peripheral blood immune cells revealed expanded TCRs (T-cell receptors) correlating with CXCR3hi CD8+ T cells in ICI myocarditis samples.

CONCLUSIONS:
These findings bring forth the CXCR3-CXCL9/10 axis as an attractive therapeutic target for ICI myocarditis treatment, and more broadly as a druggable pathway in cardiac inflammation.
Risk of Incident Atrial Fibrillation in Women With a History of Hypertensive Disorders of Pregnancy: A Population-Based Retrospective Cohort Study
Authors: Johnston Amy , Petrcich William , Smith Graeme N. , Fell Deshayne B. , Tanuseputro Peter , Coutinho Thais , Edwards Jodi D. 
Published: February 2025

BACKGROUND:
Hypertensive disorders of pregnancy (HDP) are a major cause of maternal morbidity and mortality and are associated with acute cardiac events in the peripartum period, as well as cardiovascular disease later in life. Despite the robust association between hypertension and atrial fibrillation (AFib), comparatively little is known about HDP and its subtypes as sex-specific risk factors for AFib.

METHODS:
A population-based retrospective cohort study was conducted, including 771 521 nulliparous women discharged for obstetrical delivery of their first live or stillborn singleton infant between 2002 and 2017 in Ontario, Canada. Data were obtained from record-level, coded, and linked population-based administrative databases housed at ICES. Using competing risks Cox proportional hazards regression, we estimated crude and multivariable-adjusted cause-specific hazard ratios and 95% CIs for associations between history of any HDP (and its 6 subtypes), and AFib before death, as well as all-cause mortality without a previous AFib diagnosis.

RESULTS:
Approximately 8% of women were diagnosed with HDP during the 16-year exposure accrual period. The total person-time of follow-up was 7 380 304 person-years, during which there were 2483 (0.3%) incident AFib diagnoses and 2951 (0.4%) deaths. History of any HDP was associated with an increased cause-specific hazard ratios of incident AFib and death without a previous AFib diagnosis (adjusted cause-specific hazard ratios, 1.45 [95% CI, 1.28–1.64] and 1.31 [95% CI, 1.16–1.47], respectively). These associations were observed in relatively young women (median time to event, 7 years postpartum). Associations suggestive of a dose-response relationship were observed, with more severe HDP subtypes and prepregnancy chronic hypertension associated with a 1.5 to 2.2 times higher cause-specific rate of AFib, and a 1.4 to 2.1 times higher cause-specific rate of death compared with no hypertension in pregnancy.

CONCLUSIONS:
Women exposed to HDP in their first delivery have a significantly increased cause-specific hazard ratios of incident AFib compared to their unexposed counterparts, with higher rates observed in subjects exposed to more severe de novo HDP diagnoses as well as chronic hypertension in pregnancy. These findings underscore the need to consider HDP history in risk calculation/stratification for arrhythmic and nonarrhythmic cardiovascular diseases, improve surveillance of traditional and female-specific cardiovascular disease risk factors, and develop targeted prevention strategies to reduce the occurrence and burden of HDP.
Towards Future Learning with Tangible and Embodied AI Workshops
Authors: Han Kuntong , Tang Keyang , Wang Meng 
Published: February 2025

Abstract
This article explores the transformative potential of tangible and embodied AI workshops in education, emphasizing how they can promote an intuitive understanding of an advanced AI paradigm. It presents a versatile toolkit designed for students from diverse academic backgrounds, enabling them to create controllers without prior coding experience. Integrating AI systems in the classroom does, however, raise concerns of increased expenses related to materials and teacher preparedness, as educators must adapt to guide students through interactive AI experiences rather than instruct. The article envisions a future where such workshops redefine education, providing personalized learning and heightened engagement with course material.
A Teaching Experiment on the Generation of AI-assisted Interior Renderings
Authors: Wang Changsheng , Luo Juan 
Published: February 2025

Abstract
This study explores the application of artificial intelligence (AI) to interior design education by comparing traditional and AI-assisted renderings of interior spaces by first- and third-year students at Hechi University in Guangxi, China. AI tools significantly improved the renderings made by a first-year student, but not those made by a third-year student. Our results highlight the need to prevent students from relying on the use of AI tools and hindering their development of foundational design skills. It also highlights the need to distinguish between the practicality of AI-generated renderings and the practical requirements of the design process.
Soil dynamics shaping the nematode community interactions in coastal rice ecology
Authors: Gayatri Bandaru , Rushi Kotipalli V.S.L.R. , Bapatla Kiran G. , Shyam Chunchanahalli S. , Rao Karnena K. , Panda Bipin B. , Jena Rupak 
Published: February 2025

Summary
Nematodes are predominant metazoans on earth, However, the influence of dynamic soil factors on nematode community structure, function, and soil food web interactions is one of the poorly understood areas in coastal crop ecologies. The current study area is along the coast of the Bay of Bengal in the Srikakulam district of Andhra Pradesh, India. Thirty soil samples were collected randomly and classified based on the soil salinity gradient into two soil groups: saline and non-saline soils. Other edaphic factors were recorded, such as soil pH, organic carbon, available soil nitrogen, and soluble cations (Na, Ca, Mg). The two groups differed significantly in soil pH, electrical conductivity (EC), Na, Mg and Ca content. Non-metric multi-dimensional scaling (nMDS) ordination revealed a significant grouping of nematode taxa between saline and non-saline soil samples. SIMPER analysis between the two groups demonstrated that the maximum dissimilarity was contributed by families Cephalobidae, followed by Plectidae, Merliniidae, Dorylaimidae and Rhabdolaimidae. RDA analysis with soil factors as explanatory variables revealed that soil pH, EC, Na and Mg content showed a positive correlation with bacterial functional guilds (b1, b2, b3), whereas soil organic carbon and available nitrogen showed a positive correlation towards predatory functional guilds (p4-I and o5-p). Analysis of ecological indices (basal, enrichment, structure and maturity index) and diversity indices revealed stressed food web conditions in saline soils and maturing and structured food web conditions in non-saline soils. Our study concluded that soil salinity is responsible for a significant reduction in nematode abundance and diversity besides causing considerable effects on nematode community structure and ecological functioning.
Unveiling the wood anatomy of the overlooked agarwood Aetoxylon sympetalum (Steenis & Domke) Airy Shaw (Thymelaeaceae Juss.)
Authors: Wilson Sarah D. , Terrazas Teresa , Gasson Peter E. 
Published: February 2025

Summary
Agarwood is one of the most valuable non-timber forest products due to its gratifying aroma. This has led to overexploitation of agarwood produced by species from Thymelaeaceae such as Aquilaria spp., Gyrinops spp., Gonystylus spp. and a mostly unnoticed species, Aetoxylon sympetalum. Although a candidate, A. sympetalum has not been included in CITES, in contrast with other agarwoods. This could be due to the difficulty in identifying this species because of a lack of information regarding its wood anatomy. The aim of this study is to elucidate the wood anatomy of A. sympetalum and thereby determine the features that distinguish this species from other agarwood species. Three wood samples of A. sympetalum were examined and sectioned. The resulting slides were then compared with the reference sample in the slide collection of the Jodrell Laboratory in the Royal Botanic Gardens, Kew. More samples were prepared for observation under scanning electron microscopy. The anatomical features were described according to the standard IAWA terminology. A. sympetalum is a diffuse-porous wood, with alternate and minute intervessel pits, vestured pits, very thick-walled fibres; mostly uniseriate rays and prismatic crystals within ray cells. The absence of diffusely arranged islands of phloem differentiates A. sympetalum from Aquilaria spp. and Gyrinops spp. The only noticeable difference with Gonystylus spp. is the thickness of the fibre walls which results in very high-density wood. The wood anatomy described agrees with Mandang & Wiyono (2002) but varies greatly from Tian et al. (2021) which is arguably a misidentification. This study is a reference point for identifying A. sympetalum which is paramount to its potential conservation and thus encourages its inclusion within CITES.
Assessment of commercial insect-based pet food products: nutrients’ concentration, labelling adequacy and determination of animal deoxyribonucleic acid (DNA)
Authors: Baptista da Silva C. , Santos Neto E.L. , Vermeir P. , De Leersnyder I. , Eeckhout M. , Hesta M. 
Published: February 2025

Abstract
Over recent years, the availability of insect-based pet food products has increased. However, concerns have arisen regarding potential nutritional challenges associated with using edible insects in pet food, and no studies have yet evaluated the adequacy of these products. This study assessed the nutrient composition and labelling accuracy of twenty-nine commercially available insect-based pet foods. Of these, twenty-four were dog products (four for growth, seventeen for adults, three for all life stages) and five were cat products (two for adults, three for all life stages), all labelled as complete and balanced. The products were analysed for proximate composition, essential amino acids, and mineral content (calcium, phosphorus, potassium, magnesium, copper, iron, zinc, selenium, mercury, and molybdenum) according to AOAC guidelines. The results were compared with label declarations, considering nutritional and legal tolerances, as well as recommendations from FEDIAF and NRC for the intended species and life stages (g/1000 kcal ME). Heavy metals were compared to maximum tolerable limits from the FDA. The twenty products labelled as ‘hypoallergenic’ were assessed for animal DNA using next-generation sequencing. The analysis revealed that 22 products (76%) did not comply with declared nutritional values and tolerances for at least one nutrient, with nine products (31%) showing discrepancies in two or more; key issues were in crude fibre and metabolizable energy. Three products (10%) met FEDIAF’s recommendations, and seventeen (59%) met NRC’s recommendations. Only one (3%) adhered to both label and FEDIAF’s recommendations. Most nutritional inadequacies were seen in selenium, calcium, phosphorus, Ca/P ratios, and taurine, potentially posing health risks to pets. Furthermore, fifteen out of twenty (75%) hypoallergenic-labelled products complied with the labelled species. Despite the potential benefits of insect-based pet foods, this study underscores the need for further research and stricter quality control to ensure safety and efficacy, ultimately improving pet nutrition and consumers’ trust.
A Triple Jeopardy Flood Event: Coincident Arrival of the 2022 Tonga Tsunami with a Storm Surge and Meteotsunami on the East Coast of the United States
Authors: Rabinovich Alexander B. , Šepić Jadranka , Medvedev Igor P. , Thomson Richard E. 
Published: February 2025

Abstract
On 26–27 December 2004, a major tsunami, generated by a megathrust earthquake off Sumatra Island, reached the Atlantic Coast of the United States. The arrival of the tsunami coincided with a storm-generated meteotsunami, resulting in a double jeopardy oceanic event. Similar conditions occurred on 15 January 2022, following the eruption of the Tonga-Hunga underwater volcano in the tropical Pacific. The eruption generated atmospheric pressure waves that propagated around the globe several times at roughly the speed of sound. These waves forced pronounced tsunami waves that subsequently impacted the Atlantic Coast of the United States. Almost simultaneously, a deep extratropical cyclone crossed the region on 16–17 January. The cyclone, which had formed over the northern Gulf of Mexico, propagated northeastward as a “bomb cyclone” having a rapid pressure change of 36 hPa (24 h)−1. Strong high-frequency (period < 3 h) atmospheric disturbances accompanied the cyclone. Both the large-scale low and the markedly enhanced atmospheric disturbance reached full strength in the proximity of Atlantic City during the early morning of 17 January. This combination of three hazardous events resulted in a triple jeopardy threat to water levels along the eastern seaboard of the United States, consisting of a cyclone-generated storm surge, a meteotsunami caused by high-frequency atmospheric disturbances, and a tsunami forced by the Tonga air pressure waves. Severe flooding occurred in the Atlantic City region, where sea levels rose by as much as 150 cm above background. Here, we examine the individual properties of the three atmospherically generated processes that gave rise to the cumulatively high sea level response.
Effect of sensorimotor training on stability, mobility, and quality of life after lower extremity thermal burns: A prospective randomised controlled trial
Authors: Allam Nesma M. , Abdel-Aal Nabil Mahmoud , Ali Khadra M. , Eladl Hadaya Mosaad 
Published: February 2025

Objective To determine the effect of sensorimotor training on stability, balance, mobility, quality of life, and muscle strength after lower extremity and trunk thermal burns. Design A prospective, randomised controlled trial. Setting Physiotherapy outpatient setting. Participants Sixty participants with lower extremity and trunk thermal burns, aged 20–50 years, were randomly allocated to either the Sensorimotor Training group or the Control group. Intervention The Sensorimotor Training group received both a sensorimotor training programme and a traditional physiotherapy programme, while the Control group received only the traditional physiotherapy programme. The intervention was applied three days per week for eight weeks. Outcome measures The anteroposterior stability index was the primary outcome, while secondary outcomes included the overall stability index, mediolateral stability index, Timed Up and Go Test, Berg Balance Scale, and the Short Form-36 questionnaire, all measured at baseline and after eight weeks. Results Significant differences were identified between groups after eight weeks, favouring the Sensorimotor Training group. Mean differences (95% CI) between groups were: −0.89 (−1.23, −0.54) for the anteroposterior stability index; 6.67 (4.48, 8.86) for the Berg Balance Scale; −1.7 (−2.82, −0.59) for the Timed Up and Go Test; 11.22 (7.03, 15.40) for knee extensor torque; and 7.98 (4.62, 11.35) for physical function. Conclusion Sensorimotor training, when added to a conventional physiotherapy programme, can significantly improve stability, balance, mobility, quality of life, and muscle strength compared to conventional physiotherapy alone in participants with lower extremity and trunk thermal burns.
The effect of resistance based post-activation performance enhancement interventions at different loads on maximal voluntary isometric contraction and muscle activation: Preliminary findings
Authors: Genç Sümeyye , Güdücü Çağdaş , Çek Mehmet Emre , Mancı Egemen , Günay Erkan 
Published: February 2025

Background The current literature lacks comprehensive information on how load and muscle activation affect performance in resistance exercise-based PAPE interventions. These effects remain unclear, and observations from studies focusing on both muscle activation and performance outcomes are needed to resolve this critical gap. Objective To examine the effects of PAPE interventions on maximum voluntary isometric contraction (MVIC) and muscle activation at different resistance loads via a coherence analysis approach. Methods The first experimental visit included anthropometric assessment, baseline MVIC and one repetition maximum (1RM) tests. In the next two visits, each subject completed a 5-m warm-up and performed the PAPE protocol (high Load or moderate Load) after a 5-m passive rest period. After 7-m of passive transition phase, subjects performed the MVIC and sEMG was recorded during each MVIC. Results We observed a significant load effect on peak force (p < 0.026). This difference was significant (p < 0.038) on the peak force output of the moderate load compared to the control condition, but not between the moderate and high load conditions (p < 1.000). We also observed that load had a significant effect on muscle activation (p < 0.001), and this effect was particularly significant in the high load condition (p < 0.001) compared to the control condition. Conclusion The preliminary findings of the study show that in resistance-based PAPE interventions applied at different loads, the moderate load condition positively affects the force output, while muscle activation increases more significantly, especially at high loads.
Rituximab intervention in management of thrombocytopenia in patients with systemic lupus erythematosus: A single centre experience
Authors: Toker Dincer Zeynep , Acar Beste , Ersoy Yagmur , Karali Ogulcan , Azman Feyza N , Ammar Talal , Ugurlu Serdal 
Published: February 2025

Objective Assessment of the efficacy and safety of rituximab (RTX) in treating thrombocytopenia of systemic lupus erythematosus (SLE) patients unresponsive to conventional treatments, highlighting its potential as an alternative to the expensive intravenous immunoglobulin (IVIG), and investigating the optimal number of RTX cycles for complete remission (CR). Methods A retrospective analysis was conducted on RTX utilization between 2016 and 2023 at our center. Medical records of SLE patients with thrombocytopenia, resistant to conventional treatments, were reviewed. Results 26 patients (21 females, five males) aged 52.1 ± 14.4 years were included. All patients received glucocorticoid (GC) treatment and 12 patients received IVIG before RTX administration. The median number of RTX cycles administered was 2.50 (IQR: 2-6). CR was achieved in 18 patients (69.2%), with 10 (38.5%) attaining CR during the initial treatment cycle. Four patients attained partial remission (PR), and four remained refractory. The median number of cycles needed to achieve CR during follow-up was 1.5 (IQR: 1-3.5). RTX significantly reduced the need for GCs, with only 7.7% of patients receiving prednisolone >5 mg afterward. Additionally, IVIG necessity decreased, with only 19.2% of patients requiring IVIG after completing 6 months of RTX treatment ( p < 0.046). The median platelet count significantly increased after RTX treatment ( p < 0.001) and the incidence of bleeding decreased from 76.9% to 34.6% after 6 months of RTX treatment, with none classified as life-threatening. No side effects were observed, except for hypogammaglobulinemia in one patient (3.8%). Conclusion RTX demonstrates efficacy and safety for SLE patients with thrombocytopenia unresponsive to conventional treatments, offering a potential alternative, and reducing reliance on GCs and IVIG.