bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1338 Defining the preclinical changes of microbial composition, gut barrier function, and subclinical inflammatory markers associated with future risk of ulcerative colitis
Authors: Bharali B , Li Q , Xue M , Guttman D , Madsen K , Griffiths A , Panaccione R , Verdu E F , Moayyedi P , Turpin W , Croitou K , Lee Dr. S H ,   The GEM Project Research Consortium
Published: January 2025

Abstract

Background
Ulcerative colitis (UC) is a chronic inflammatory condition of the rectum and colon with a complex aetiology involving genetic, immune, and microbial factors. Less is known about the pre-disease phase of UC compared to Crohn’s disease (CD). Investigating the preclinical biomarkers that precede the development of UC may provide insights into its pathogenesis.

Methods
Participants were recruited as part of the CCC-GEM project, a prospective cohort study following healthy first-degree relatives (FDR) of patients with CD. Baseline gut inflammation was assessed using faecal calprotectin (FCP), with a cut-off of 100ug/g, while baseline gut permeability was assessed by the fractional urinary excretion ratio of lactulose-to-mannitol (LMR). Baseline faecal microbiome composition was analyzed using 16s rRNA sequences, and functional pathways were inferred using PICRUSt2. Cox proportional hazards models were used to assess the association of baseline variables with UC onset, adjusting for age, sex, and family clustering. Significance was determined using p-values and false discovery rate-adjusted q-values.

Results
Among 3,596 FDRs, 16 developed UC during a median follow-up of 6.88 years. FDRs with elevated baseline FCP had a 3.1-fold higher risk (p=0.02) of developing UC, while no significant association was observed between baseline LMR and UC onset.
The relative abundance of genus Bilophila (HR=0.33 per SD, q=0.010) and Bifidobacteria (HR=0.16, q=0.02) were associated with UC risk, but lost significance after adjusting for FCP. Interestingly, the relative abundances of genera Alistipes (HR=0.15, q=0.0007), Phascolarctobacterium (HR=0.08, q=0.027), Christensenellaceae R.7 group (HR=8.37, q=0.02) and Angelakisella (HR=5.28, q=0.004) remained significantly associated with risk of UC even after adjusting for FCP.
Thirty-seven pathways, predominantly involved in specific metabolic processes such as carbohydrates, lipid, or folate metabolism, were also associated with UC risk. Fur example, pathways involving hydroxymethylglutaryl-CoA reductase (HR=0.44, q=0.03), choline monooxygenase (HR=0.22, q=0.005), and 3-phenylpropionate/trans-cinnamate dioxygenase (HR=4.70, q=0.001) remained significantly associated with UC risk even after adjusting for FCP.

Conclusion
We report that elevated FCP, but not LMR, was significantly associated with future risk of UC. Furthermore, specific microbial taxa and functional pathways exhibited strong associations with future risk of UC, independent of FCP. These microbial signatures were distinct from the previously reported pre-CD microbial changes, suggesting a unique gut microbial contribution to the development of UC.

References
Raygoza Garay JA, Turpin W, Lee S-H, et al. Gastroenterology 2023;165:670–681.
P1346 Response to biologic treatment in patients with Crohn’s disease is associated with consistent decreased antibody response to bacterial flagellins
Authors: Leibovitzh H , Krongauz D , Schlesinger Y , Hirsch A , Ron Y , Thurm T , Godneva A , Weinberger A , Cohen N A , Segal E , Maharshak N 
Published: January 2025

Abstract

Background
Patients with Crohn’s disease (CD) exhibit over-representation of antibody-bound peptides derived from bacterial flagellins. Using longitudinal measurements prior to and during treatment, we aimed to assess serum antibody response to bacterial flagellins and related fecal microbial alterations associated with response to treatment.

Methods
Thirty-nine patients with active CD (Harvey-Bradshaw Index [HBI]&gt;4 or fecal calprotectin [FCP]&gt;150μg/g) commencing biologic treatment (Anti-TNF 56.4%, Ustekinumab 20.5%, Vedolizumab 23.1%) between 1/2018 to 6/2021 in a single tertiary center were included in this study. Serum and stool samples were collected at baseline and during treatment at weeks 14, 22 and 52 (30, 25 and 14 patients with pre-and post- treatment samples, respectively). Remission was defined as HBI≤ 4 and FCP≤ 150. Serum samples were analyzed using high-throughput phage-display immunoprecipitation sequencing (PhIP-Seq) to assess antibody response to microbial flagellins. Fecal samples were assessed by DNA shotgun metagenomic sequencing to obtain microbial compositional data. PhIP-Seq data was analyzed using the Wilcox-test on the mean fold change and microbial data was analyzed using a multivariable linear regression mixed effects model.

Results
Median age of the cohort was 33.0 [IQR 27.0;46.5] and 19 (48.7%) were females (Table 1). Antibody response against bacterial flagellins was significantly attenuated in patients achieving remission vs. non-remission at all time points (p&lt;0.05) (Figure 1). Remission was associated with change in the abundances of several individual species compared to baseline, including decreased abundance of Ruminococcus_A.sp003011855, Ruminococcus_B gnavus, Klebsiella pneumoniae and Veillonella parvula_A and increased abundance of Roseburia intestinalis, whereas non-remission was associated with increased abundance of Sutterella wadsworthensis (q&lt;0.05 or consistent direction of effect at all different time points). Moreover, most of these taxa belonged to the Lachnospiraceae and Enterobacteriaceae family and Roseburia genera which are the target of anti-flagellin antibodies.

Conclusion
Response to biological treatment in patients with CD is associated with consistent decreased antibody response to bacterial flagellins and related fecal microbial alterations compared to non-responders. These findings support the role of anti-bacterial flagellins as a potential marker for treatment response and needs to be further validated in larger cohorts.
P1349 Fungal profile of the gut colon - a new tool in diagnostics of ulcerative colitis remission
Authors: Tarasova G , Zubova A 
Published: January 2025

Abstract

Background
Numerous studies show structural and quantitative changes in the bacterial microbiota of the colon in different phases of ulcerative colitis (UC) and its relationship with the pathogenesis and prognosis of the disease. However, in addition to bacterial community dysbiosis, patients with UC exhibit changes in the composition of the fungal microbiota, which allows it to be considered from the standpoint of a non-invasive method for predicting disease remission.

Methods
The study included 21 patients (ages from 20 to 41, 13 men and 8 women) in the relapse stage of UC - left-sided UC with mild to moderate activity (Truelov-Witts scale, Mayo index); and 20 patients (ages from 26 to 52, 10 men and 10 women) in the stage of clinical endoscopic remission. Gut microbiota was assessed by sequencing of the 18S ribosomal RNA.

Results
A logistic regression model was evaluated to predict UC remission. In cases of achieving clinical endoscopic remission of the disease, a statistically significant increase in the levels of Malassezia and Blastocystis genera and a decrease in Aspergillus were recorded. The results of the model evaluation are presented in Table 1.
The model is statistically significant according to the chi-square criterion (p=0.008), the Cox and Snell determination pseudo-coefficient is 0.449, Nagelkerk – 0.599. The sensitivity and specificity of the model are 0.8 (Fig. 1).
The indicators show that this model has sufficient predictive ability.

Conclusion
Analysis of the gut mycobiota profile in different phases of the course of UC allowed to determine a model for predicting remission - an increase in the levels of the Malassezia and Blastocystis genera and a decrease in the Aspergillus genus, which constitutes a new non-invasive method for monitoring the course of the disease.
Citizen science contributions to the investigation of extralimital tropical and subtropical marine fish distribution via Gulf Stream transport
Authors: O’Neill Michael E , Bluhm Samantha C , Nichols Owen C 
Published: January 2025

ABSTRACT
The Gulf Stream exerts tremendous influence over oceanographic conditions in the northwestern Atlantic as it transports tropical water to higher latitudes. While the meandering eddies and warm core rings of the Gulf Stream persist year-round, the seasonal warming of coastal waters in the northwestern Atlantic afford many young-of-year tropical and subtropical species temporary refuge through the summer and fall after Gulf Stream dispersal. Several aspects of this dispersal and its impact on coastal ecosystems are difficult to document. Due to the broad scale and intensive sampling effort required to survey these expatriated species, we used a citizen science platform to gather species observations. We analyzed over 1,200 reports of fish from 28 taxonomic families to describe extralimital geographic distributions, observation frequency, and phenological aspects of their dispersal. The influence of ecosystem dynamics and life stage-specific biological characteristics on the observed extralimital distributions of species is discussed. We found that citizen scientists gathered novel sightings relevant to coastal marine fish ecology through a variety of coastal activities, and complimentary to established research methods. These findings support incorporating crowd-sourced data to improve our understanding of marine species assemblages of the northwestern Atlantic.
Influence of birthplace and age at migration on cognitive aging among Hispanic/Latino populations in the U.S.: Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA)
Authors: Liu Mao-Mei , Stickel Ariana M , Tarraf Wassim , Li Lehan , Perreira Krista M , Riosmena Fernando , Lamar Melissa , Testai Fernando D , Gallo Linda C , Garcia Tanya P , Llibre-Guerra Jorge J , Isasi Carmen R , Lipton Richard B , Daviglus Martha , Dow William H , González Hector M 
Published: January 2025

Abstract

Background and Objectives
While Hispanic/Latino populations in the U.S. are remarkably diverse in terms of birthplace and age at migration, we poorly understand how these factors are associated with cognitive aging. Our research seeks to operationalize a life course perspective of migration and health and contribute new understanding of Alzheimer’s disease / Alzheimer’s disease related dementias among U.S.-based Hispanic/Latino older adults.

Research Design and Methods
Harnessing the Hispanic Community Health Study/Study of Latinos (n=16,415) and the Study of Latinos-Investigation of Neurocognitive Aging (n=6,377) data, we compare baseline cognition and 7-year cognitive change among U.S./mainland-born Hispanic/Latino adults relative to foreign/island-born immigrants by age of migration (four groups: born in mainland U.S., immigrated &lt;16 years, 16-34 years, &gt;34 years). Global cognition was calculated as a composite measure, and domain specific measures were considered in secondary analyses. We employed linear regressions, ANOVA contrasts and Blinder-Oaxaca decomposition techniques.

Results
All Hispanic/Latino immigrant adults, regardless of age at migration, have a cognitive health disadvantage (at each visit and over time) relative to U.S./mainland-born Hispanic/Latino individuals. Differences did not endure the inclusion of covariates and were explained predominantly by first socio-economic and then acculturative factors, and far less by health and health behaviors. Acculturative factors are particularly important for individuals who migrated after childhood.

Discussion and Implications
Socio-economic and acculturation factors have outsized roles in explaining gaps in cognitive aging among U.S.-born and migrant Hispanic/Latino adults. It is then vital to examine whether disrupting socio-economic and acculturation inequalities closes such gaps in cognitive aging.
Bone quality in Pycnodysostosis: micropetrosis, locally distorted osteocyte lacuno-canalicular network and heterogenous mineralization pattern in an adult female patient with multiple fractures
Authors: Fratzl-Zelman Nadja , Blouin Stéphane , Kornak Uwe , Hartmann Markus A , Kurth Andreas A , Zwerina Jochen 
Published: January 2025

Abstract
Pycnodysostosis is a very rare skeletal dysplasia caused by biallelic loss-of-function mutations in cathepsin K, a proteolytic enzyme highly expressed by osteoclasts. Deficiency of cathepsin K impairs bone resorption, and bone remodeling and leads to progressive osteosclerosis and bone fragility. Moreover, cathepsin K is also expressed by mature osteocytes. Whether the density, size and viability of osteocytes and the osteocyte lacuno-canalicular network (OLCN) are also altered and thereby impact bone quality in pycnodysostosis has not been explored.
We used light microscopy, quantitative backscattered electron imaging and confocal laser scanning microscopy to examine bone material obtained from a 57-year-old female patient obtained during surgical correction after femoral head fracture.
The cortex consisted of a compact shell of multilayered collagen fibrils oriented in parallel to the periosteum reflecting vigorous primary bone apposition, multiple osteons with concentrically ordered lamellae and scattered patches of woven bone. The trabecular area was very dense with BV/TV, varying locally from 30.3% to 67.4%. The bone matrix was overmineralized (average calcium content: +7.5% versus reference values, with a fivefold increase of highly mineralized areas &gt;27 weight % calcium). Numerous multinucleated osteoclasts and fringes of demineralized matrix were viewed on bone surfaces.
The density (number/mm2: 193 to 223) and area (20 μm2) of the osteocyte lacunae and their canalicular length (0.05 μm/μm3 bone volume) were within normal range. However, numerous bone packets exhibited (hyper)mineralized osteocyte lacunas (micropetrosis) resulting in a locally disrupted OLCN.
In summary, our data indicate that in pycnodysostosis not only osteoclast function is impaired but also osteocyte viability is decreased, leading to micropetrosis, distorted OLCN and heterogenous mineralization pattern. Thus, osteoclasts and osteocytes both contribute to reduce bone quality. However, the presence of a dense osteocyte network in large areas of the sample indicates that cathepsin K is not essential for the formation of the OLCN.
Engineered allogeneic stem cells orchestrate T lymphocyte driven immunotherapy in immunosuppressive leptomeningeal brain metastasis
Authors: Kanaya Nobuhiko , Seddiq Waleed , Chen Kok-Siong , Kajiwara Yoshinori , Moreno Lama Lucia , Borges Paulo , Kuroda Shinji , Wakimoto Hiroaki , Shah Khalid 
Published: January 2025

Abstract

Background
Immune-checkpoint inhibitors have shown clinical benefit in non-small cell lung cancer (NSCLC) derived brain metastasis (BM), however, their efficacy in lung to leptomeningeal brain metastasis (LLBM) remains poor.

Methods
A paired matched RNA expression dataset of patients with NSCLCs and BMs was analyzed to idenfiy BM specific suppressive tumor microenvironment (TME) features. Next, we created immune-competent LLBM mouse models that mimic clinical LLBM. We evaluated the efficacy of intrathecal (IT) delivery of allogeneic stem cells (SCs) engineered to release single-chain variable fragment anti-PD-1 (scFvPD-1). To enhance tumor cell killing and subsequent modulation of the immune TME, we explored the therapeutic activity of dual SCs releasing oncolytic herpes simplex virus (oHSV) and scFvPD-1 and profiled immune and metabolic consequences.

Results
RNA sequencing analysis of primary NSCLCs and BMs revealed an immune-suppressive TME with reduced immune cells and increased PD-1+ T cells in BMs. We showed significantly decreased immune cells and increased PD-1+ T cells in the TME of LLBM compared to primary NSCLC tumors in LLBM mouse tumor models. Next, we showed that locoregional IT treatment with SC releasing scFvPD-1, but not conventional systemic injection of anti-PD-1 antibody, suppressed tumor growth and improved survival in our immune-competent LLBM models. Furthermore, dual SCs releasing oHSV and scFvPD-1 (SC-oHSV/scFvPD-1) enhanced therapeutic outcomes by inducing oHSV-mediated immunogenic cell death, activating anti-tumor T cell signaling, and disrupting oxidative phosphorylation, which sensitized tumors to cisplatin.

Conclusion
Locoregional delivery of SC-oHSV/scFvPD-1 effectively targets the immune-suppressive TME in LLBM, providing a promising strategy for treating LLBM.
Anal melanoma: a clinical challenge without therapeutic consensus
Authors: Fuentes-Calvo Kevin J , Alvarez-Bautista Francisco E , Santes Oscar , De Nora-Jiménez Renata , Arias-Ruíz Luis F , Salgado-Nesme Noel 
Published: January 2025

Abstract
Anal melanoma is a rare malignancy, accounting for 0.4% to 1.6% of all melanomas. Its atypical presentation, low incidence, and non-specific symptoms make it a challenging diagnosis, which can lead to delayed treatment with an unfavorable impact on clinical outcomes. Treatment should be multidisciplinary and may include surgical resection with adjuvant therapy, chemotherapy, and radiotherapy. We present the case of a male patient who presented to the emergency department due to foreign body sensation and transanal bleeding. The patient underwent an anal exploration under anesthesia, where a hyperpigmented canal-dependent tumor lesion with extension into the perianal skin was found. After a wide local excision, histopathological study confirmed the diagnosis of invasive nodular melanoma. The patient was discharged without complications for follow-up and management in the outpatient medical oncology clinic.
Epstein-Barr virus Infection Exacerbates Ulcerative Colitis by Driving Macrophage Pyroptosis via the Upregulation of Glycolysis
Authors: Ma Chunxiang , Chen Kexin , Li Lili , Jiang Mingshan , Zeng Zhen , Yin Fang , Yuan Jing , Jia Yongbin , Zhang Hu 
Published: January 2025

Abstract

Background
Epstein-Barr virus (EBV) infection is associated with clinical symptoms, treatment response, need for surgical intervention, and an enhanced likelihood of lymphoma among patients with ulcerative colitis (UC). However, existing studies have primarily concentrated on the epidemiological and clinical associations between EBV and UC, leaving the mechanisms by which EBV exacerbates colitis poorly understood.

Methods
Clinical specimens of UC patients with EBV infection and a mouse model of dextran sulfate sodium (DSS)-induced colitis with concurrent murine γ-herpesvirus 68 (MHV-68) infection were utilized to investigate the relationship between EBV infection and macrophage pyroptosis. In vivo, adoptive transfer of MHV-68-induced macrophages and macrophage depletion were performed to elucidate the underlying mechanisms. In vitro, myeloid leukemia mononuclear cells of human (THP-1) and macrophages derived from mouse bone marrow (BMDMs) were stimulated with EBV and MHV-68, respectively, to assess macrophage pyroptosis and glycolysis.

Results
EBV-induced activation of macrophage pyroptosis was positively correlated with clinical disease activity in UC patients. Furthermore, MHV-68 infection activated pyroptosis by upregulating Gasdermin D, NLRP3, interleukin-1β, and interleukin-18 in colonic tissues and peritoneal macrophages of mice with colitis. In vitro, EBV and MHV-68 also mediated activation of pyroptosis in human THP-1 cells and mouse BMDMs, respectively. Additionally, the adoptive transfer of MHV-68-induced BMDMs aggravated murine colitis, whereas macrophage depletion attenuated MHV-68-induced intestinal injury. Mechanistically, MHV-68 promoted macrophage pyroptosis by upregulating glycolysis, while the glycolysis inhibitor, 2-Deoxy-d-glucose, blocked this process in vitro.

Conclusion
EBV infection exacerbates UC by driving macrophage pyroptosis through upregulation of glycolysis, indicating a potential therapeutic approach to mitigate EBV-induced intestinal inflammation.
Fixed drug eruption in a cribriform pattern: an atypical presentation
Authors: Mathur Mahesh , Thakur Neha , Regmi Sandhya , Paudel Supriya , Bhattarai Nabita , Karki Sambidha 
Published: January 2025

Abstract
Fixed drug eruption (FDE) is a distinct adverse drug reaction characterized by a well-defined, dusky, violaceous to erythematous patch that recurs at the same site upon re-exposure to causative drugs and resolves with hyperpigmentation. This unique reaction is a type IV hypersensitivity reaction mediated by memory CD8+ T cells that reside in the basal layer of the epidermis of the resting FDE lesion. Variants of FDE described in the literature include bullous, generalized bullous, nonpigmenting, linear, papular, erythema multiforme-like, transitory giant, annular, psoriasiform, erythema dyschromicum perstans-like and cellulitis-like. We present the case of a 12-year-old boy with FDE in a cribriform pattern that has not been defined so far.
Detection of Non-cardiac Fetal Abnormalities on Ultrasound at 11–14 Weeks: Systematic Review and Meta-analysis
Authors: Karim J.N. , Di Mascio D. , Roberts N. , Papageorghiou A.T. ,   for the ACCEPTS study
Published: January 2025

(Abstracted from Ultrasound Obstet Gynecol 2024;64:15–27)
First-trimester ultrasound scans are traditionally used to confirm fetal viability, establish gestational age, identify multiple pregnancies, and screen for trisomies, whereas second-trimester scans focus on detecting other congenital abnormalities. Advances in ultrasonography suggest the potential for detecting certain anomalies during first-trimester screening, though the accuracy of this approach remains uncertain.