bluuebunny/crossref_metadata_2025_split huggingface dataset:
IHIBITION OF TRNA QUEUOSINE MODIFICATION CAUSE MITOCHONDRIAL DYSFUNCTION AND APOPTOSIS IN THE INTESTINAL EPITHELIAL CELLS
Authors: Ran Di , Zhang Yong-guo , Sun Jun 
Published: January 2024

Abstract

BACKGROUND
Transfer RNA (tRNA) modifications occur through the action of specific enzymes that recognize and modify the nucleotides within the tRNA molecule. Queuine tRNA-ribosyltransferase catalytic subunit 1 (QTRT1) and QTRT 2 co-localize in mitochondria and form a heterodimeric TGT participating in tRNA Queuosine (tRNA-Q) modification. Our previous study demonstrated that Q-tRNA modification plays a novel role in regulating barrier functions of intestinal epithelial cells. However, the roles of tRNA-Q modifications in the maintenance of intestinal mitochondrial homeostasis and the progression of inflammatory bowel disease (IBD) are still unclear.

METHODS
We used QTRT1 knockout (KO) mice and cultured cell lines with QTRT1 knockdown (KD) to investigate the impact and mechanism of tRNA-Q modifications in intestinal mitochondrial homeostasis and inflammation.

RESULTS
Initially, we confirmed QTRT1's mitochondrial localization through immunofluorescence co-localization with Mitotracker staining in QTRT1 KD CaCO2-BBE cells. Then we used flow cytometry MitoSox Red staining and revealed an increase in mitochondrial ROS production in QTRT1 KD cells. Furthermore, we observed heightened mitophagy both in vitro and in the colon of QTRT1KO mice, evident through significantly enhanced fusion of Mtphagy Dye-labeled mitochondria with lysosomes, and altered mitochondrial proteins (Tomm20, LC3, and Cytochrome C) via Western Blotting. Notably, we identified an increase in apoptosis in the QTRT1 KO mice evidenced by the upregulation of phosphorylated PARP, cleaved Caspase 3, and the Bax/BCL-2 ratio in colonic mitochondrial proteins. TUNEL staining corroborated this apoptosis increase specifically in the colon due to the QTRT1 deficiency.

CONCLUSIONS
Reduced QTRT1 induced dysfunctional mitochondria and Caspase-3 dependent apoptosis. tRNA-Q modification plays an unexplored role in the pathogenesis of mitochondrial function in the intestine. Our upcoming research will employ N-acetyl-l-cysteine, a mitochondrial ROS inhibitor, and a Caspase 3 specific inhibitor to ascertain the role of tRNA modification in mitochondrial function in the intestinal inflammation. Insights into tRNA-Q modification will pave the road for new therapeutic strategies to restore mitochondrial function in IBD.
COMPARATIVE ASSESSMENT OF BIOBANK DATASETS FOR THE STUDY OF INFLAMMATORY BOWEL DISEASE
Authors: Nett Bri , Beckloff Nicholas , Wimberley Jack , Hargarten Chris , Zahiri Javad , Peterson Matt , Faber Ashley , Sarangi Srikant , Wark Barry 
Published: January 2024

Abstract
Lack of available multiomics datasets has slowed progress in understanding the relationship between genomic variants, gene expression, and disease progress in inflammatory bowel disease (IBD). Biobanks provide an opportunity to produce population-scale datasets to accelerate understanding of these diseases. Ovation’s IBD Omic Data is a multiomic dataset including whole-genome sequencing (WGS) and RNA sequencing (RNA-seq) from disease and normal tissues, derived from clinical biopsies of patients with IBD. Omic data is supplemented with patient phenotypic data including diagnoses, therapies, procedures, and routine laboratory results. We report initial results of analysis of the first 212 patients from this cohort to identify genes differentially expressed between disease and normal colon tissue in patients with IBD, and to explore variants in these genes in both the Ovation IBD Omic Data and UK Biobank (UKBB) genomic data.
To generate Ovation IBD Omic Data, DNA and RNA were extracted from fixed formalin paraffin embedded (FFPE) tissue samples of 212 IBD patients. Sequencing was conducted at a depth of 30X WGS. RNA-seq analysis was performed at a depth of 30M 1x50-bp reads per sample. Subsequent analysis was done via STAR aligner, FeatureCounts, and DESeq2. We curated a list of 54 common genes implicated in IBD from the literature as a benchmark. WGS data in the Variant Call Format (VCF) were ingested into the REVEAL platform along with phenotypic data variables. Values for minor allele frequencies (maf) were calculated and annotations were generated using the Ensembl Variant Effect Predictor (VEP).
We examined the number of unique genomic variants in coding regions of the Ovation IBD Omic Data compared to those from the UKBB dataset for the benchmark genes. Despite the difference in sample population size, the Ovation data included a median of ~3,600 more unique variants per gene (~85% had more variants identified in a population of 212). Analysis of the global gene expression levels from Ovation’s IBD dataset showed 18 genes from the benchmark had significantly different expression in disease and normal tissue (p-value &lt;0.001) across all IBD patients. We also analyzed the subset of samples from patients with CD (n=58). Notably, SLC4A4 and IFITM3 did not pass the original threshold in the full analysis (p-values were &gt;0.001), however they were statistically significant when the analysis was limited to CD patients (p-value &lt;0.0001).
Comparing datasets of varying complexity shows that, despite a smaller sample size, specialized data derived from clinical samples, such as the Ovation IBD Omic Data, can provide additional insights for complex diseases like IBD. Further analysis will focus on the relationship between unique genomic variants identified, expression profiles and associated metadata to identify candidates of potential clinical relevance.
UNDERSTANDING HOW PATIENTS WITH MODERATE-TO-SEVERE ULCERATIVE COLITIS DESCRIBE THE SPECTRUM OF BOWEL URGENCY DEFINITIONS: RESULTS FROM QUALITATIVE RESEARCH
Authors: Dubinsky Marla , Hunter Theresa , Stassek Larissa , Harding Gale , Stefan Marissa , Fikre Tsion , Bleakman Alison Potts , Moses Richard 
Published: January 2024

Abstract

BACKGROUND
Bowel urgency, the sudden or immediate need to have a bowel movement, is a burdensome symptom to patients with ulcerative colitis (UC). The objective of this study was to understand how adult patients with moderately-to-severely active UC describe bowel urgency remission and “no or minimal” bowel urgency.

METHODS
Qualitative phone interviews were conducted with adults with HCP-confirmed moderately-to-severely active UC. The interview included open-ended questions that elicited participant perceptions of bowel urgency remission, “no or minimal” and “normal” bowel urgency. Participants indicated which score on the 11-point Urgency Numeric Rating Scale (Urgency NRS; 0 [no urgency] to 10 [worst possible urgency]) they would use to describe “no or minimal” and “normal” bowel urgency. Participants were recruited from 6 clinical sites based in the United States. ATLAS.ti was used to organize the data. Descriptive statistics were used for sociodemographic and clinical characteristics.

RESULTS
19 adults with moderately-to-severely active UC participated in this study. Participants had a mean age of 48.1 years, 63% were female, 74% were white, and 58% were employed full-time. All participants had experienced bowel urgency and 79% (n=15/19) confirmed they had experienced a bowel-urgency related accident in the past. Most participants (n=18/19; 95%) defined bowel urgency remission as “feeling normal” with fewer bowel movements and reduced levels of bowel urgency and 4 participants (21%) defined bowel urgency remission as having a “good day” (Table 1). The impact of bowel urgency remission included the ability to partake in social/leisure activities and feeling less anxious overall (Table 2).
Participants selected scores from 0 to 5 on the 11-point Urgency NRS to describe “no or minimal” bowel urgency with 5 (26%) indicating that “0 to 4” was the appropriate range, whereas 5 (26%) selected “0 to 2”. Other participants selected “0 to 3” (n=3/19; 16%), “0 to 1” (n=2/19; 11%), “0” (only) (n=2/19; 11%), “1 to 2” (n=1/19; 5%), and “0 to 5” (n=1/19; 5%). The majority of participants (n=15/19; 79%) described feeling “normal” and having minimal impacts when experiencing “no or minimal” bowel urgency. Participants were also asked to indicate the highest score on the Urgency NRS at which they could still consider their bowel urgency to be “normal” and 42% of participants (n=8/19) selected 5 as the highest score that they would still consider as “normal.”

CONCLUSION
These interviews provided evidence that among patients with moderately-to-severely active UC, bowel urgency can still be considered “no or minimal”, “normal” or in “remission” even when some amount of bowel urgency is present. In general, responses of “0” to “5” on the Urgency NRS were considered to correlate to “no or minimal” or “normal” bowel urgency.
AEROMONAS IMMUNE MODULATOR PROTEINS INTERACT WITH HOST LIPOCALIN-2 TO MEDIATE INFLAMMATION THROUGH BOTH HOST- AND MICROBIOME-SPECIFIC MECHANISMS
Authors: Robinson Catherine , Sweeney Emily , Davidson Jennifer , Guillemin Karen 
Published: January 2024

Abstract
Inflammatory bowel diseases (IBD) are a prevalent and growing clinical health problem worldwide. The etiology of IBD involves complicated interactions between immunological genetic variants, environmental factors, and the intestinal microbiome. Current therapies for IBD include corticosteroids and biologics, which can ameliorate overproduction of pro-inflammatory cytokines, and other inflammatory mediators, but which do not treat the microbiome dysbiosis that often triggers or propagates inflammation. Therefore, an urgent need exists for more effective therapies for IBD that treat both inflammation and microbiome dysbiosis. Health-associated microbes are under-explored sources of mechanisms that maintain tissue and immune homeostasis. Our research team at the University of Oregon has identified a novel family of anti-inflammatory proteins secreted by a zebrafish gut symbiont, Aeromonas, which we named Aeromonas immune modulator (Aim) proteins. Host Lipocalin-2 (LCN2) limits the growth of tissue-resident microbes through sequestration of iron, an essential micronutrient, by binding bacterial iron-laden siderophore molecules. Aim proteins allow the zebrafish symbiont Aeromonas to overcome this LCN2-mediated iron starvation. Structurally, Aim proteins contain lipocalin folds and we discovered that Aims and LCN2 physically interact, suggesting that Aim proteins allow Aeromonas to recapture siderophores sequestered by LCN2. In addition to supporting the growth of Aeromonas in the zebrafish intestine, Aim proteins decrease host tissue inflammation both in microbially-induced and injury models. In the context of infection with a zebrafish pathogenic Vibrio, Aim proteins decrease tissue inflammation while simultaneously increasing Vibrio growth, suggesting that Vibrio exploits Aim proteins to overcome nutritional immunity and down-regulate programs of tissue destruction. In addition to siderophores, LCN2 and other LCNs binds a wide array of hydrophobic molecules, including immunomodulatory lipid hormones such as prostaglandins. We hypothesize that Aim proteins exert their diverse effects on bacterial growth and tissue homeostasis through their binding to LCN2 and other LCNs. This work suggests a new molecular mechanisms through which resident microbes promote tissue homeostasis by counteracting nutritional immunity, alleviating bacterial tissue destruction, and dampening the action of pleotropic host immunomodulatory LCNs. Furthermore, Aim proteins have the potential to be developed as a novel therapeutic for IBD, unique in its ability to both target a primary mediator of inflammation, neutrophils, and facilitate restoration of microbiome dysbiosis.
3D MORPHOGENESIS AND BACTERIAL CO-CULTURE IN A CANINE GUT-ON-A-CHIP USING BIOPSY-DERIVED INTESTINAL ORGANOIDS FROM HEALTHY AND IBD PATIENTS
Authors: Nagao Itsuma , Nakazawa Meg , Ambrosini Yoko 
Published: January 2024

Abstract
The understanding of the role of intestinal bacteria in various intestinal diseases has been limited due to the lack of suitable in vitro models. However, recent advancements in Gut-on-a-Chip culture technology provide a promising avenue for exploring complex interactions between intestinal epithelium and bacteria. In this study, we aimed to create a microfluidic Gut-on-a-Chip co-culture system using dogs as a model. Dogs share similarities with humans in terms of intestinal disease pathophysiology, clinical presentations, and intestinal microbiome, making them a relevant model for various intestinal diseases, including inflammatory bowel disease (IBD).
We cultured colonoids from both healthy dogs and dogs with IBD on the Gut-on-a-Chip platform to create villus-like structures under dynamic conditions. Co-cultures with non-pathogenic Escherichia coli (NPE) were established in the Gut-on-a-Chip with healthy colonoids, and we conducted a static Transwell (TW) co-culture for comparison. To assess epithelial barrier integrity, we measured transepithelial electrical resistance (TEER), and we evaluated the expression of ZO-1, a tight junction protein, through immunofluorescence staining (IF).
Following 6-9 days of uninterrupted medium flow in the Gut-on-a-Chip models, we observed sporadic clusters of villus-like structures (i.e., 3D morphogenesis) in canine intestinal epithelial cells in both the models derived from healthy dogs and those with IBD. The IF confirmed the presence of ZO-1, indicating the establishment of tight junctions. Infection with NPE in the TW system resulted in a significant reduction in TEER (48.2±4.4% at 12 hours and 7.3±5.3% at 24 hours). In contrast, the Gut-on-a-Chip maintained TEER levels at 100.3±12.8% at 12 hours, 94.9±2.2% at 24 hours, and 88.8±15.0% at 48 hours, preserving the 3D structure.
The innovative canine Gut-on-a-Chip model, capable of reproducing villus-like structures and preserving a 3D configuration using both healthy and diseased organoids (specifically, IBD), presents a valuable platform for investigating bacterial-epithelium interactions in both human and veterinary medicine. This dynamic microfluidic culture system enables the co-cultivation of living bacteria while maintaining epithelial integrity, facilitating the study of intricate interactions between intestinal bacteria and epithelial crosstalk.
Appropriate Use of Medical Interpreters in the Breast Imaging Clinic
Authors: Feliciano-Rivera Yara Z , Yepes Monica M , Sanchez Priscila , Kalambo Megan , Elahi Fatima , Wahab Rifat A , Jackson Tatianie , Mehta Tejas , Net Jose 
Published: January 2024

Abstract
More than 25 million Americans have limited English-language proficiency (LEP) according to the U.S. Census Bureau. This population experiences challenges accessing health care and is least likely to receive preventive health care, including screening mammogram. In a setting where the breast radiologist does not speak the language of their patient, using certified medical interpreter services is fundamental. Medical interpreter use is associated with improved clinical care and patient satisfaction and can potentially increase adherence to screening mammograms and follow-up in patients with LEP. Title VI of the Civil Rights Act requires interpreter services for patients with LEP who are receiving federal financial assistance. Failure to provide interpretative services when necessary is considered discriminatory and illegal. The use of untrained medical interpreters, including ad hoc interpreters (eg, family, friends, or untrained staff), is associated with more medical errors, violation of confidentiality, and poor health outcomes. Types of medical interpretation services available to address language barriers include in-person interpretation, telephone and video remote interpretation, and qualified bilingual staff. Proper training and certification of medical interpreters is essential to prevent misinterpretations and ensure patient safety. When using an interpreter service, speak to and maintain eye contact with the patient, address the patient directly and seat the interpreter next to or slightly behind the patient, use visual aids whenever possible, and have the patient repeat the information to verify comprehension. Breast radiologists can address disparities in breast cancer screening and treatment by promoting effective communication.
Bone microarchitecture and strength assessment in adults with osteogenesis imperfecta using HR-pQCT: normative comparison and challenges
Authors: Bevers M S A M , Harsevoort A G J , Gooijer K , Wyers C E , Feenstra J , van Rietbergen B , Boomsma M F , van den Bergh J P , Janus G J M 
Published: January 2024

Abstract
Data on bone microarchitecture in osteogenesis imperfecta (OI) are scarce. The aim of this cross-sectional study was to assess bone microarchitecture and strength in a large cohort of adults with OI using high-resolution peripheral quantitative computed tomography (HR-pQCT) and to evaluate challenges of using HR-pQCT in this cohort. Second-generation HR-pQCT scans were obtained at the distal radius and tibia in 118 men and women with Sillence OI type I, III, or IV using an extremity-length-dependent scan protocol. In total, 102 radius and 105 tibia scans of sufficient quality could be obtained, of which 11 radius scans (11%) and 14 tibia scans (13%) had a deviated axial scan angle as compared with axial angle data of 13 young women. In the scans without a deviated axial angle and compared with normative HR-pQCT data, Z-scores at the radius for trabecular bone mineral density (BMD), number, and separation were −1.6 ± 1.3, −2.5 ± 1.4, and −2.7 (IQR: 2.7), respectively. They were −1.4 ± 1.5 and −1.1 ± 1.2 for stiffness and failure load and between ±1 for trabecular thickness and cortical bone parameters. Z-scores were significantly lower for total and trabecular BMD, stiffness, failure load, and cortical area and thickness at the tibia. Additionally, local microarchitectural inhomogeneities were observed, most pronounced being trabecular void volumes. In the scans with a deviated axial angle, the proportion of Z-scores &lt;−4 or &gt;4 was significantly higher for trabecular BMD and separation (radius) or most total and trabecular bone parameters (tibia). To conclude, especially trabecular bone microarchitecture and bone strength were impaired in adults with OI. HR-pQCT may be used without challenges in most adults with OI, but approximately 12% of the scans may have a deviated axial angle in OI due to bone deformities or scan positioning limitations. Furthermore, standard HR-pQCT parameters may not always be reliable due to microarchitectural inhomogeneities nor fully reflect all inhomogeneities.
Comparative impact of bacitracin and select feed additives in the feeding program of Lohmann LSL-Lite pullets at the onset of lay through to 31 weeks of age
Authors: Kiarie Elijah G , Cheng Veronica , Tan Zhigang , Chen Wenzhen , Xu Xiangyi , Peng Yu , Liu Haijun , Qin Zonghua , Peng Xianfeng 
Published: January 2024

Abstract
There are limited investigations on the role of feed additives in easing transition of pullets to egg production phase. We investigated the effects of supplementation of bacitracin methylene disalicylate (BMD) and select feed additives (myristic acid [MA], benzoic acid [BA], and Aspergillus niger probiotic [PRO]) in feeding program for pullets from the onset of lay through to 31 weeks of age (woa). Parameters measured included hen-day egg production (HDEP), feed intake (FI), feed conversion ratio (FCR), egg quality characteristics, ceca microbial activity, apparent retention of components, and plasma metabolites. A total of 1,200 Lohmann LSL Lite pullets were procured at 18 woa and placed in enriched cages (30 birds/cage) based on body weight (BW) and allocated to five diets. The diets were a basal diet formulated to meet specifications or basal mixed with either BMD, MA, BA, or PRO. Birds had free access to feed and water throughout the experiment. Between 18 and 20 woa, birds fed BMD ate a similar (P &gt; 0.05) amount of feed to BA birds, but more (P = 0.0003) than birds fed basal, MA, or PRO diets. Basal birds had lower HDEP (P = 0.001) and lighter eggs (P &lt; 0.0001) than birds fed any of the feed additives between 21 and 31 woa. The basal hens had a higher (P = 0.009) abundance of Escherichia coli than birds fed BMD, BA, and PRO diets. Consequently, BMD, BA, and PRO birds had a higher (P = 0.011) Lactobacilli: E. coli ratio (LER) than hens fed the basal diet. Specifically, relative to basal-fed hens, the LER of the BMD, MA, BA, and PRO hens was higher by 37%, 21%, 26%, and 45%, respectively. Moreover, birds fed PRO tended to have a higher concentration of ceca digesta acetic acid (P = 0.072) and a lower concentration of isobutyric acid (P = 0.096). In conclusion, supplementing pullet diets with broad-spectrum antibiotics or feed additives (MA, BA, and PRO) had a positive impact on FI, and egg production linked to modulation of indices of gut health. The results suggested supplementing feed additives in feeding programs for pullets at the onset of lay can bolster productivity outcomes.
Evolving Forehead Augmentation: A Five-step Approach with High G Prime Hyaluronic Acid
Authors: Huang Yau-Li , Liang Ben Chung-Pin 
Published: January 2024

Background:
Achieving effective upper-face rejuvenation through forehead augmentation is essential; however, complications such as vascular occlusion leading to skin necrosis or vision loss can occur. The complex forehead anatomy, characterized by ligaments and septa, often results in uneven outcomes with dermal filler treatment. The learning curve for successful forehead augmentation was longer than that anticipated. Herein, we present a specialized program for clinicians to expedite the learning process. This study explores a five-step technique for forehead augmentation using high elastic (G prime) hyaluronic acid fillers.

Methods:
We enrolled 10 Asian female participants with no history of dermal filler injections, surgery, or nonsurgical forehead procedures. All participants provided written informed consent, and their progress was assessed using photography and the Global Aesthetic Improvement Scale.

Results:
Immediate post-treatment Global Aesthetic Improvement Scale ratings averaged 3.0 ± 0.0, decreasing to 2.5 ± 0.5 at 6 months, and 1.8 ± 0.6 at 12 months. Mild tenderness (10%), temporary swelling (30%), and a rapid recovery period underscored the safety and reliability of our approach. Importantly, no adverse vascular events were observed.

Conclusions:
Our five-step injection technique utilizing high-G prime hyaluronic acid leverages a profound understanding of the forehead anatomy, systematic methodology, and dynamic potential of advanced fillers. By implementing this paradigm, plastic and reconstructive surgeons can increase the standards of forehead augmentation and consistently achieve harmonious and effective results.