bluuebunny/crossref_metadata_2025_split huggingface dataset:
Twelve-Month Outcomes of Faricimab for Patients With Sub-optimally Responsive Diabetic Macular Oedema in a UK Tertiary Referral Centre
Authors: El-Badawi Kamal , Scrivens Benjamin , Eke Oluwaniyi , Ismail Rehab , Kobayter Lina , Salvatore Serena 
Published: December 2024

AbstractPurposeEvaluating 12-month visual and anatomical outcomes after switching to faricimab in diabetic macular oedema (DMO) patients with sub-optimal response to aflibercept 2mg.Patients and methodsSixty-two eyes of fifty patients were enrolled in this retrospective study at a UK tertiary referral centre. This consisted of DMO patients with sub-optimal response to aflibercept 2mg who were switched to faricimab. Four loading injections of faricimab were given at monthly intervals, followed by a treat-and-extend regime. The sub-optimal response was defined as CST >325 microns or >20% from best CST despite aflibercept 2mg at less than or equal to 8 weekly intervals(≤q8w) having completed a loading dose of aflibercept 2 mg (6 injections at monthly intervals). Outcome measures were best-recorded visual acuity (BRVA), central subfield thickness (CST), and treatment intervals.ResultsBaseline BRVA was 67.6 (±11.8) letters and CST was 406.4 (±105.9) µm, and the mean treatment interval was 6.5 (±1.8) weeks. At baseline, 24.2% of eyes were treated every 4 weeks (q4w), 19.4% every 6 weeks (q6w), and 56.5% every 8 weeks (q8w). After the 4thfaricimab loading dose, 54 patients continued on treat-and-extend faricimab. BRVA improved to 70.4 (±12.7) letters (p=0.007) while CST reduced to 372.8 (±132.0)µm (p=0.070). The mean injection interval improved to 7.4 (±2.6), 95%CI[0.1, 2.9]weeks. Subjects were followed up for 57.1 (±19.7) weeks, with a mean of 7.92 (±2.53) faricimab injections. At the latest follow-up, BRVA was stable at 68.7 (±14.6)(p=0.918) letters. CST had reduced further to 343.1 (±117.5) µm(p=0.034). Treatment intervals at the latest follow-up were: 3.2% q4w, 9.7% q6w, 30.6% q8w, 3.2% q10w, 11.3% q12w, 1.6% q14w, 6.5% q16w, with 53.2% on ≥q8w. The mean injection interval had also improved to 9.2 (±3.1) weeks(p=0.122).ConclusionIn this study, DMO patients with sub-optimal response to aflibercept 2mg experienced improved anatomical outcomes and extended treatment intervals while maintaining vision by switching to faricimab.
Distinct DNA Methylation Signatures in Maternal Blood Reveal Unique Immune Cell Shifts in Preeclampsia and the Pregnancy-Postpartum Transition
Authors: Jamshed Laiba , Smith Keaton W , Wilson Samantha L 
Published: December 2024

1.0AbstractPreeclampsia (PE) is a hypertensive disorder of pregnancy characterized by immune dysregulation and significant risks to maternal and fetal health. While current management relies on high-risk patient monitoring and early diagnosis, these methods are costly and burdensome, especially for low-risk pregnancies. There is a pressing need for non-invasive tools to predict and monitor PE. DNA methylation (DNAm) is a type of DNA modification that influences gene expression, and has been associated with immune cell dynamics and PE pathogenesis. This study explores whether DNAm-based immune cell composition profiling can provide insights into PE-related immune dysregulation. We conducted a search in the Gene Expression Omnibus (GEO) for DNA methylation datasets using Illumina 27K, 450K, and EPIC arrays from maternal blood in both healthy and PE pregnancies. We found two studies that met our criteria, involving a total of 24 healthy pregnancies and 14 with PE. To estimate the composition of immune cells (including CD8T, CD4T, Monocytes, Natural Killer, Neutrophils, Eosinophils, and B cells) based on DNA methylation data, we employed the R package EpiDISH. We used a linear model to compare statistical differences in the proportions of immune cells between PE cases and the control group. Longitudinal trends were also examined to capture immune cell shifts from pregnancy to postpartum. We found that monocyte proportions were significantly reduced in preeclamptic pregnancies compared to normotensive pregnancies (p=0.013). No significant differences were observed in other immune cell types, including T cells, B cells, neutrophils, eosinophils, and natural killer cells. Longitudinal analyses revealed substantial immune cell shifts in the postpartum period, including increased monocytes, B cells, CD4+ T cells, and CD8+ T cells, emphasizing the importance of gestational age in immune dynamics. These findings support DNAm profiling as a valuable tool for understanding immune cell dynamics in PE. Reduced monocyte proportions in PE highlight the role of immune dysregulation in its pathogenesis. Longitudinal sampling provides additional insights into the evolution of immune changes throughout pregnancy and postpartum, offering potential for developing predictive and monitoring tools for PE. Future studies with larger, more diverse cohorts are essential to refine the utility of DNAm in pregnancy complications.
The CCL17-CCR4 axis is critical for mutant STAT6-mediated microenvironmental remodelling and therapeutic resistance in Relapsed/Refractory Diffuse Large B Cell Lymphoma
Authors: Abraham Madelyn J. , Guilbert Cynthia , Gagnon Natascha , Goncalves Christophe , Benoit Alexandre , Rys Ryan N. , Preston Samuel E. J , Morin Ryan D. , Miller Wilson H. , Johnson Nathalie A. , del Rincon Sonia V. , Mann Koren K. 
Published: December 2024

AbstractRelapsed and refractory Diffuse Large B Cell Lymphoma (rrDLBCL) presents a significant challenge in hematology-oncology, with approximately 30-40% of DLBCL patients experiencing relapse or resistance to treatment. This underscores the urgent need to better understand the molecular mechanisms governing therapeutic resistance. Signal Transducer and Activator of Transcription 6 (STAT6) has been previously identified as a gene with recurrent D419 gain-of-function mutations in rrDLCBL. When STAT6D419mutations are present in DLBCL tumour cells, we have demonstrated that transcription of the chemokine CCL17 (aka TARC) is increased, and tumours have increased infiltration of CD4+ T cells. However, the significance of increased T cell infiltration had not been determined. In the present study, we developed a mouse model of STAT6D419Nmutant DLBCL, that recapitulates the critical features of human STAT6D419mutant DLBCL, including increased expression of phospho-STAT6, increased CD4+ T cell invasion, and resistance to doxorubicin treatment. With this model, we found CD4+ T cells in STAT6D419Ntumours have higher expression of the receptor for CCL17, CCR4. Usingex vivofunctional assays we demonstrate that STAT6D419Ntumour cells are directly chemoattractive to CCR4+ CD4+ T cells, and when CCR4 is inhibited using a small molecule antagonist, CD4+ T cells in STAT6D419Ntumours are reduced and STAT6D419Ntumours regain therapeutic sensitivity to doxorubicin. Using PhenoCycler imaging of human rrDLBCL samples, we find that STAT6D419tumours indeed have increased expression of phospho-STAT6+ and increased cellular interactions between phospho-STAT6+ tumour cells and CD4+/ CCR4+ CD4+ T cells. Thus, our data identify CCR4 as an attractive therapeutic target in STAT6D419mutant rrDLBCL.
The pyrethroid insecticide deltamethrin disrupts neuropeptide and monoamine signaling pathways in the gastrointestinal tract
Authors: White Alexandria C. , Krout Ian N. , Mouhi Sabra , Chang Jianjun , Kelly Sean D. , Caudle W. Michael , Sampson Timothy R. 
Published: December 2024

AbstractEnteroendocrine cells (EECs) are a rare cell type of the intestinal epithelium. Various subtypes of EECs produce distinct repertoires of monoamines and neuropeptides which modulate intestinal motility and other physiologies. EECs also possess neuron-like properties, suggesting a potential vulnerability to ingested environmental neurotoxicants. One such group of toxicants are pyrethroids, a class of prevalent insecticides used residentially and agriculturally. Pyrethroids agonize voltage-gated sodium channels (VGSCs), inducing neuronal excitotoxicity, and affect the function of monoamine-producing neurons. Given their anatomical location at the interface with the environment and their expression of VGSCs, EECs likely represent a vulnerable cell-type to oral pyrethroid exposure. In this study, we used the EEC cell line, STC-1 cells, to evaluate the effects of the common pyrethroid deltamethrin on the functional status of EECs. We find that deltamethrin impacts both expression of serotonergic pathways and inhibits the adrenergic-evoked release of an EEC hormone, GLP-1,in vitro. In a mouse model of oral exposure, we found that deltamethrin induced an acute, yet transient, loss of intestinal motility, in both fed and fasted conditions. This constipation phenotype was accompanied by a significant decrease in peripheral serotonin production and an inhibition of nutrient-evoked intestinal hormone release. Together, these data demonstrate that deltamethrin alters monoaminergic signaling pathways in EECs and regulates intestinal motility. This work demonstrates a mechanistic link between pyrethroid exposure and intestinal impacts relevant to pyrethroid-associated diseases, including inflammatory bowel disease, neurodegenerative disease, and metabolic disorders.
Cassini: Streamlined and Scalable Method for in situ profiling of RNA and Protein
Authors: Lapique Nicolas , Kim Michael , Thom Nicholas , Nadaf Naeem M. , Pineda Juan , Macosko Evan Z. 
Published: December 2024

AbstractIn the expanding field of spatial genomics, numerous methods have emerged to decode biomolecules in intact tissue. Advanced techniques based on combinatorial decoding can resolve thousands of features in a reasonable time but are often constrained by either the prohibitive costs associated with commercial platforms or the complexity of developing custom instruments. Alternatively, sequential detection methods, like single-molecule FISH, are easier to implement but offer limited multiplexing capability or signal amplification. Here, we introduce Cassini, a new approach for straightforward, cost-effective multiplexed measurements of mRNA and protein features simultaneously. Cassini leverages rolling circle amplification (RCA), known for its robust amplification and remarkable stability even after intense stripping, to serially detect each feature in under 20 minutes of total experimental time. The method also enables simultaneous immunostaining with either fluorophore-conjugated or DNA-barcoded antibodies, through an optimized immunostaining buffer. In a single overnight run, we show that Cassini can quantify 32 features (comprising both RNA and proteins) with sensitivity similar to state-of-the-art FISH techniques. We provide a comprehensive protocol alongside an online probe-design platform (cassini.me), aiming to enhance accessibility and user-friendliness. With our open-source solution, we aspire to empower researchers to uncover the nuances of spatial gene expression dynamics across diverse biological landscapes.
Characterization of both major histocompatibility complex classes in a wild social mammal: the banded mongoose
Authors: Schubert Nadine , Nichols Hazel J. , Mwanguhya Francis , Businge Robert , Kyambulima Solomon , Mwesige Kenneth , Cant Michael A. , Winternitz Jamie C. 
Published: December 2024

ABSTRACTThe major histocompatibility complex’s (MHC) role in the vertebrate adaptive immune response and its exceptional polymorphism make it a key target for studying adaptive gene evolution. However, previous studies on carnivore MHC have mostly focused on populations which experienced a severe bottleneck or are of general conservation concern. Hence, sample sizes are often small and generalizations about MHC diversity are unreliable. Furthermore, studies often focus on one MHC class and do not cover the whole peptide binding groove of the MHC molecule. Here, we characterize MHC class I (MHC-I) exon 2 and 3, encoding both the α1- and α2-domain of the MHC-I molecule, as well as MHC-II DRB exon 2 for a large sample (N = 282-485) of a wild mammal of least conservation concern, the banded mongoose. We found that MHC-I generally showed higher allelic diversity and polymorphism compared to MHC-II, which is in line with findings in humans that show higher diversifying selection acting on MHC-I. However, MHC-I exon 3 showed the lowest diversity, possibly due to its different role in generating the peptide binding groove of the class I molecule compared to exon 2. Moreover, we found selection to act more strongly on MHC-I exon 2 (domain α1) than exon 3 (domain α2). Despite frequent inbreeding, phylogenetic comparative analysis showed banded mongooses to have MHC diversity levels comparable with other carnivores of least concern. Phylogenetic analysis indicated a longer evolutionary trajectory for MHC-II compared to MHC-I as well as species-specific gene duplication of nonclassical sequences of MHC-I clustering with classical sequences. Trans-species polymorphism was detected for nonclassical MHC-I sequences suggesting homology or convergent evolution for these genes. Our study is the first to characterize both MHC classes of a social, wild carnivore using a high throughput sequencing approach with a large sample size and thereby provides the basis for further investigation of MHC structure and function within the banded mongoose and other carnivores.
Effect of Redcurrant (Ribes rubrum) fruit powder on patients with COVID-19, A randomized double-blinded clinical trial
Authors: Pirmorad Azadeh Ahmadi , Ebadipour Sakineh , Amiri-Sadeghan Amir , Zarredar Habib , Asadi Milad , khalili Majid , Sharifi Akbar 
Published: December 2024

AbstractIntroductionCOVID-19 has affected many people worldwide. Effective treatments have been reported using medicinal plants which their multi functionality may beneficial. Considering the importance of innate immune response and pathologic effect of cytokine storm in COVID-19 patients, this study examined the effect of Redcurrant (Ribes rubrum) fruit powder capsules on inflammatory cytokines of IL-6 and TNFα as primary objectives. Moreover, its effect on the COVID-19 patients’ recovery symptoms was evaluated.MethodsWe analyzed the clinical effect on recovery symptoms, hematological parameters, and the serum levels of interlucin-6 and TNFα in the placebo-controlled and treated patients with Redcurrant fruit powder.ResultsRedcurrant fruit powder capsules significantly decreased pro-inflammatory cytokines of IL-6 and TNF-α, and reduced the clinical recovery time of COVID-19 and fatigue (from 7.3 ± 2.09 to 2.9 ± 1.28 days) as well as cough (from 5.67 ± 2.4 to 2.4 ± 1.7) days compared to the control group.ConclusionRedcurrant fruit powder might be a promising herbal treatment of COVID-19, and since no considerable side effect is observed in short-term usage, it might be beneficial to start treatment as early as possible in suspected cases of COVID-19.
Widespread genetic testing control inherited polycystic kidney disease in cats
Authors: Ukawa Hisashi , Kida Akane , Ataka Kai , Horie Ryo , Matsumoto Yuki 
Published: December 2024

AbstractA genetic variant ofPKD1in cats, which causes polycystic kidney disease (PKD), is a target for direct-to-consumer genetic testing to assess PKD risk; however, its effect on genetic structure in cat populations remains unexplored. Therefore, in this study, we aimed to examine the changes in feline PKD and thePKD1variant across breeds and over time using a large dataset of 110,325 insured and 61,968 genetic-tested cats from 14 breeds. Results revealed that thePKD1variant frequency significantly decreased, with a reduction of 42.6% before 2019 and after 2022. Systematic genomic analysis revealed no differences in genetic structure or inbreeding levels. The effective population size of cats with thePKD1variant decreased between points. Overall, these findings highlight the potential of direct-to-consumer genetic testing in promoting more optimized breeding practices and enhancing feline welfare.
Anti-inflammatory assessment of zinc oxide nanoparticles mediatedAframomum citratum(C. Pereira) K. Schum (Zingiberaceae) in Wistar rats
Authors: Eya’ane Meva Francois , Nga Essama Denise Murielle , Nguemfo Edvige Laure , Bamal Hans-Denis , Ntoumba Agnes Antoinette , Ebanda Kedi Phillipe Belle , Yen Beglau Thi Hai , Tako Djimefo Alex Kevin , Djuidje Annie Guilaine , Tchatchouang Geordamie Chimi , Nanga Chick Christian , Nyuyfoni Gildas Fonye , Tchangou Njimou Armel Florian , Madeleine Evouna Danielle Ines , Mintang Fongang Armel Ulrich , Janiak Christoph 
Published: December 2024

AbstractIntroductionZinc oxide nanoparticles (ZnONPs) have been synthesized using a wide range of techniques, including green chemistry, because of their versatility, cost effectiveness, and environmentally friendly nature, offering thereby interesting and inexpensive therapeutic options. This study aimed to develop zinc oxide nanoparticles as an anti-inflammatory agent usingAframomum citratumseed extract.MethodologyZnONPs were prepared by the reaction between zinc nitrate and an alkalineaqueous extract ofA. citratumseeds. The isolated nanoparticles were then characterized using UV-Vis, FTIR, SEM/EDX, PXRD and TEM techniques. The toxicological profile was assessed at a limited dose of 2000 mg/kg in rats, and methods for heat denaturation of egg albumin, stabilization of red blood cell membranes and inhibition of carrageenan-induced plantar oedema were studied to assess anti-inflammatory properties.ResultsThe formation of ZnONPs was observed by a color change and the appearance of the plasmon resonance peak at 360 nm in the UV-Vis spectrum while FTIR confirmed the presence of secondary metabolites; SEM confirmed the presence of multiform aggregates, and TEM visualize point like particles. EDS confirmed the presence of Zn atoms within the synthetized material. The toxicological profile studied showed no harmful signs; zinc oxide nanoparticles synthesized fromA. citratumseed extract showed high inhibition percentages of 86 (1mg/mL); 77 (0.6mg/mL) and 79(1mg/mL) when subjected to inhibition of heat-induced egg albumin denaturation, red cell membrane stabilization and oedema induction by carrageenan respectively, not significatively different compared with diclofenac sodium as positive controls.ConclusionZinc oxide nanoparticles synthesized and characterized fromA. citratumseed extract act as a potent anti-inflammatory agent and are devoid of acute oral toxicity.
Using a Multilingual AI Care Agent to Reduce Disparities in Colorectal Cancer Screening: Higher FIT Test Adoption Among Spanish-Speaking Patients
Authors: Bhimani Meenesh , Baker R. Hal , Ausin Markel Sanz , Meixiong Gerald , Lasko Rae , Raglow-Defranco Mariska , Miller Alex , Mukherjee Subhabrata , Godil Saad , Cook Anderson , Agnew Jonathan D. , Atreja Ashish 
Published: December 2024

AbstractBackgroundColorectal cancer (CRC) screening rates remain disproportionately low among Hispanic and Latino populations. While artificial intelligence (AI) has shown promise in healthcare delivery, its impact on health equity remains unclear.ObjectiveTo evaluate the effectiveness of a bilingual generative AI voice agent outreach program in engaging Spanish-speaking patients for CRC screening compared to English-speaking patients.MethodsWe conducted a retrospective analysis of AI-powered outreach calls for CRC screening at a large integrated health system serving central Pennsylvania and northern Maryland in September 2024. The study included 1,878 patients (517 Spanish-speaking, 1,361 English-speaking) eligible for colorectal cancer screening. The AI care agent conducted personalized phone calls in the patient’s preferred language to discuss screening and facilitate fecal immunochemical test (FIT) kit requests. The primary outcome was FIT test opt-in rate. Secondary outcomes included call connect rates and duration.ResultsSpanish-speaking patients demonstrated significantly higher engagement across all measures compared to English-speaking patients: FIT test opt-in rates (18.2% vs. 7.1%, p<0.001), connect rates (88.8% vs. 53.3%, p<0.001), and call duration (6.05 vs. 4.03 minutes, p<0.001). In multivariate analysis, Spanish language preference remained an independent predictor of FIT test opt-in (adjusted OR 2.012, 95% CI 1.340-3.019, p<0.001) after controlling for demographic and other factors (gender, age, state of residence, and call duration).ConclusionsContrary to concerns about technology exacerbating disparities, AI-powered outreach achieved significantly higher engagement among Spanish-speaking patients. These findings suggest that language-concordant AI interactions may help address healthcare disparities and improve preventive care engagement in traditionally underserved populations.
Epidemiology ofVibrio CholeraeInfections in the Households of Cholera Patients in the Democratic Republic of the Congo: PICHA7 Prospective Cohort Study
Authors: George Christine Marie , Sanvura Presence , Namunesha Alves , Bisimwa Jean-Claude , Endres Kelly , Felicien Willy , Williams Camille , Trivedi Shubhanshi , Davis Kilee L. , Perin Jamie , Sack David A. , Bengehya Justin , Maheshe Ghislain , Cikomola Cirhuza , Bisimwa Lucien , Leung Daniel T. , Mwishingo Alain 
Published: December 2024

AbstractBackgroundThe aim of this prospective cohort study is to build evidence on transmission dynamics and risk factors forVibrio choleraeinfections in cholera patient households.MethodsHousehold contacts of cholera patients were observed for 1-month after the index cholera patient was admitted to a health facility for stool, serum, and water collection in urban Bukavu in South Kivu, Democratic Republic of the Congo. AV. choleraeinfection was defined as aV. choleraebacterial culture positive result during the 1-month surveillance period and/or a four-fold rise in aV. choleraeO1 serological antibody from baseline to the 1-month follow-up.ResultsTwenty-seven percent of contacts (134 of 491) of cholera patients had aV. choleraeinfection during the surveillance period. Twelve percent (9 of 77) of cholera patient households had a stored water sample withV. choleraeby bacterial culture, and 7% (5 of 70) had a water source sample withV. cholerae. Significant risk factors for symptomaticV. choleraeinfections among contacts were stored food left uncovered (Odds Ratio (OR): 2.39, 95% Confidence Interval (CI): 1.13, 5.05) and younger age (children <5 years) (OR: 2.09, 95% CI: 1.12, 3.90), and a drinking water source with >1 colony forming unitE.coli/ 100mL (OR: 3.59, 95% CI: 1.46, 8.84) forV. choleraeinfections.ConclusionsThe findings indicate a high risk of cholera among contacts of cholera patients in this urban cholera endemic setting, and the need for targeted water treatment and hygiene interventions to prevent household transmission ofV. cholerae.SummaryIn this prospective cohort study in the Democratic Republic of the Congo, the majority of cholera patient households had multipleVibrio choleraeinfected household members and both source water and stored drinking water samples hadV. cholerae.