bluuebunny/crossref_metadata_2025 huggingface dataset:
MITOCHONDRIAL DYSFUNCTION CAUSES CECAL PATCH (CP) INFLAMMATION IN ULCERATIVE COLITIS
Authors: Patel Parth H , Hassan Syed Adeel , Kasem Ahmad , Wempe Lesley , Elsayed Mohamed , Bhogoju Sarayu , Goretsky Tatiana , Lee Goo , Barrett Terrence , Kapur Neeraj
Published: January 2024

BACKGROUND

Up to 17% of distal ulcerative colitis (UC) patients have discontinuous (proximal) inflammation referred to as Cecal Patch (CP), associated with greater abdominal pain, bleeding and diarrhea. Despite these known associations, the pathogenesis of CP lesions is poorly understood. Recent data suggest that reduced mitochondrial (Mito) function predicts unfavorable clinical outcomes in active UC (Haberman et al; Nat Comm 2019). We posit that inflammation and tissue injury induced in UC-associated CP involves Mito dysfunction.

METHOD

UC patients with/without cecal disease and normal controls were biopsied. Tissue from CP lesions or normal caecum were collected in Allprotect® (AP) and formalin. Total RNA from AP-preserved biopsies were used for cDNA synthesis and RT-qPCR for Mito complexes, cytokines, anti-oxidant and calcineurin (CaN) signaling genes and tissue processed for IHC for Mito complexes.

RESULT

Transcriptomic analysis showed significant downregulation in genes associated with Mito biogenesis (PGC1α, TFAM, NRF2) and Mito complexes (Ndufa1, Ndufa4, Ndufb2, Ndufb6, mtCO1, mtCO2, Cox5B, Cox6A1, ATP5A1, ATP5B, ATP5E) in CP lesions compared to normal caecum from active patients. Major regulators of Mito biogenesis (PGC1α and TFAM) revealed ~39% and ~24% reductions of mRNA respectively, while NRF2 (anti-oxidant regulator) showed ~62% reduced mRNA in CP lesions compared to normal cecum from distal UC patients. Electron transport chain complex mRNAs showed 31%, 47%, and 48% reduction in complex I (Ndufa1, Ndufa4, Ndufb2, Ndufb6), complex IV (mtCO1, mtCO2, Cox5B, Cox6A1), and complex V (ATP5A1, ATP5B, ATP5E) levels, respectively in CP lesions compared to normal controls. Concomitantly, the IHC staining also showed significant reductions in Ndufb6, MTCO1 and Cox5A protein levels in CP lesions compared to normal cecum sections. The CP-related decreased markers of Mito biogenesis and function correlates with increased proinflammatory cytokine mRNA (IL-6: 2-fold; TGFβ1: 1.6-fold; IL-2: 2.6-fold) and decreased anti-inflammatory (IL10: 3.2-fold) gene expression in CP lesions. Further investigation demonstrated that repressed Mito function in CP lesions is associated with downregulation of anti-oxidant genes (SOD1, SOD2, Prdx3, Gpx4, Trx2) compared to normal cecum. Inflammation-induced Mito dysfunction in CP lesions also stimulates CaN signaling as demonstrated by significant increases in mRNA levels of CaN and downstream regulated genes (Cathepsin-L, Rel-A Glut4, CREB-BP and Igf-1r).

CONCLUSION

These data represent the first indication that Mito dysfunction occurs in CP associated with distal UC. Furthermore, we speculate that Mito dysfunction-induced CaN signaling promotes regional (CP) inflammatory responses. These important findings indicate that targeting Mito metabolism may be an important therapeutic goal of treating UC patients with CP.
NANOPARTICLE ENCAPSULATION OF THE SPECIALIZED PRO-RESOLVING MEDIATOR MARESIN-2: A NOVEL APPROACH FOR PROMOTING MUCOSAL REPAIR IN THE INTESTINE
Authors: Miranda-Guzman Jael , Morris Aaron , Quiros Miguel , Brazil Jennifer , Parkos Charles , Nusrat Asma
Published: January 2024

Epithelial cells form protective barriers at mucosal surfaces and play a critical role in maintaining tissue homeostasis. Active inflammation in inflammatory bowel disease (IBD) is associated with epithelial barrier disruption and mucosal erosions/wounds that contribute to the inflammatory response and disease symptoms. Therefore, efficient repair of epithelial erosions/wounds is crucial for restoring intestinal barrier function and resolving mucosal inflammation. In response to injury, epithelial cells proliferate and migrate to cover denuded surfaces and restore critical barrier properties. Resident and recruited immune cells at sites of injury release factors that play an important role in orchestrating mucosal repair. Bioactive lipid mediators released by leukocytes, including leukotrienes and specialized pro-resolving mediators (SPMs), regulate epithelial signaling pathways to influence mucosal repair processes. Liquid chromatography-mass spectrometry (LCMS) analyses of healing colonic mucosal wounds performed to detect SPMs identified high levels of MaR2 in healing colonic wounds. In vitro studies using primary colonic epithelial cells revealed MaR2-driven increases in epithelial wound repair that were potentiated by the pro-inflammatory cytokines TNFα and IFNγ. While MaR2 increased epithelial migration by activating cell matrix adhesion proteins, including Src-paxillin and focal adhesion kinase, we did not observe any influence of MaR2 on the activation of cyclin D1/D2 or on epithelial proliferation. Importantly, in vivo studies demonstrated enhanced colonic mucosal wound repair and recovery from dextran sulfate-induced colitis in mice administered MaR2. Given the thermolabile nature of MaR2 (and associated ultracold storage requirements), thermostable polylactic acid (PLA) nanoparticles (NP) containing MaR2 (PLA MaR2) were generated. PLA MaR2 nanoparticles retained bioactivity following extended storage at room temperature and exhibited potent effects on in vivo colonic biopsy induced wound repair. Taken together these data reveal that thermostable MaR2 containing nanoparticles represent a promising new therapeutic approach for regenerating epithelial barrier function and restoring mucosal homeostasis in individuals with IBD.
CD11B/CD18 SIALYLATION REGULATES NEUTROPHIL TRAFFICKING AND INFLAMMATORY FUNCTION IN THE INTESTINE
Authors: Brazil Jennifer , Azcutia Veronica , Kelm Matthias , Cummings Richard , Parkos Charles
Published: January 2024

Pathogen-triggered neutrophil (PMN) recruitment is critical for innate immunity, but excessive PMN influx and associated mucosal tissue damage is implicated in the pathogenesis of numerous human inflammatory disorders including inflammatory bowel disease (IBD). Critically in both ulcerative colitis and Crohn’s disease, disease flares requiring medical intervention are associated with migration of large numbers of PMNs across colonic epithelium resulting in mucosal injury/ulceration. Recent studies have shown that specific PMN glycans can be targeted to reduce transepithelial migration (TEpM) the critical final step in PMN intestinal trafficking. However the role of Sialic acid (Sia), the most abundant PMN expressed terminal glycan, in regulating PMN migration and inflammatory function in the gut is not well understood. Using sophisticated models of human and murine PMN intestinal migration, we show that blocking sialidase-mediated removal of alpha 2-3 linked sialic acid from CD11b/CD18 inhibits PMN TEpM in vitro and in vivo.Measurement of cytochrome C reduction revealed that inhibition of sialidases reduced bacterial peptide (fMLF) stimulated superoxide release by human and murine PMN. Flow cytometry analyses revealed that sialidase inhibition decreased fMLF mediated PMN degranulation and fMLF mediated CD11b/CD18 conformational activation. Highlighting the functional importance of individual Sia residues, inhibition of alpha 2-3 sialidase activity with 3’ Sialyllactose (3’SL) was found to inhibit PMN intestinal trafficking in vitro and in vivo and reduce PMN degranulation responses. Immunoblotting studies showed that sialidase inhibition deactivates spleen tyrosine kinase (Syk) and p38 MAP kinase, key intracellular mediators that signal downstream of PMN CD11b/CD18. Finally, inhibition of sialidase activity reduced adhesion of PMN to ICAM-1 (a major physiological substrate of CD11b/CD18) demonstrating that endogenous PMN sialidases regulate binding interactions between migrating PMN and intestinal epithelial receptors. Taken together data show that upon activation PMN sialidases remove alpha 2-3 Sia from CD11b/CD18 which leads to integrin activation and subsequent outside in signaling mediated by Syk to drive PMN inflammatory effector functions including migration, degranulation, and superoxide release. As such targeting CD11b/CD18 sialylation represents a promising new therapeutic strategy for reducing dysregulated PMN influx and associated mucosal tissue damage in IBD and other inflammatory disorders.
BREASTFEEDING STATUS AND DISEASE SEVERITY IN PEDIATRIC PATIENTS WITH ULCERATIVE COLITIS: AN EXPLORATORY RETROSPECTIVE COHORT STUDY
Authors: Glick Abigail , Horwitz Bruce , Snapper Scott , Ouahed Jodie
Published: January 2024

OBJECTIVE

While the protective effect of being breastfed on the development of ulcerative colitis has been well established, it is not known if being breastfed decreases colectomy rate and disease severity for pediatric patients. This work is designed to better understand the connection between breastfeeding status and disease severity of ulcerative colitis among pediatric patients.

METHODS

This exploratory retrospective cohort study analyzed the clinical and laboratory data of patients at Boston Children’s Hospital enrolled in a data registry and biorepository since 2012. Data was collected from charts and analyzed to determine if there is a significant difference in colectomy rate, pediatric ulcerative colitis activity index (PUCAI) score, ESR, or CRP, between not breastfed (n=56), breastfed (n=39), and mixed breastfed patients (n=31). Breastfed patients are defined as patients who were exclusively breastfed for greater than or equal to three months. Patients who were never breastfed were considered not breastfed. Patients who were exclusively breastfed for less than three months or received a mix of formula and breastfeeding were considered mixed breastfed. Statistical analysis of the groups was performed using a one-way ANOVA.

RESULTS

At disease diagnosis, the average PUCAI score of the not breastfed group (32.4) was significantly higher than the exclusively breastfed group (18.4) (p value = 0.0189). No significant difference was detected in the average PUCAI score of the mixed breastfed group (34.1) compared to the not breastfed group (32.4). Significant differences in the colectomy rate between all three groups were not detected, and likewise we did not find significant differences in markers of disease severity including ESR, CRP, and hemoglobin at diagnostic visit between groups.

CONCLUSION

These results suggest that children with ulcerative colitis who were exclusively breastfed have a lower average PUCAI score at the time of diagnosis than those who were not breastfed. Further investigation with larger data sets may be necessary to determine other benefits of exclusive breastfeeding in pediatric ulcerative colitis patients.
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

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

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 <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 >0.001), however they were statistically significant when the analysis was limited to CD patients (p-value <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

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

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

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

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

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 <−4 or >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

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 > 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 < 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.
Trends of Surgery, Patient, and Surgeon Characteristics for Corneal Transplants in the Medicare Population From 2011 to 2020
Authors: Webb Khala , Dun Chen , Dai Xi , Chen Ariel , Srikumaran Divya , Makary Martin A. , Woreta Fasika A.
Published: January 2024

Purpose:

The aim of this study was to describe recent trends in corneal transplants and patient and surgeon characteristics for corneal transplants that occurred in the Medicare population.

Methods:

This was a retrospective, cross-sectional study using Current Procedural Terminology codes. We identified Medicare Fee-For-Service (FFS) claims for different types of corneal transplant procedures performed on Medicare beneficiaries aged 65 years or older from 2011 to 2020. Number and types of corneal transplants performed each year and patient and surgeon demographics and characteristics were analyzed.

Results:

We analyzed 148,981 corneal transplants performed by 2972 surgeons within the study period. Most corneal transplants performed were endothelial keratoplasties (70.1%). Most patients were women (60.3%) and White (85.8%). 18.2% of patients lived in a rural area, whereas only 3.5% of transplants occurred in a rural area and 5% of surgeons practiced in a rural area. Male surgeons represented 77.8% of all surgeons and performed 84.9% of all corneal transplants in the study period. The proportion of corneal transplants performed by female surgeons gradually increased over time, from 12.1% in 2011 to 19.0% in 2020. The proportion of female surgeons also increased from 16.2% in 2011 to 23.8% in 2020. Most surgeons (67%) performed <6 corneal transplants per year.

Conclusions:

Although the number of female corneal transplant surgeons has increased over time, women remain underrepresented in the surgical workforce. Further investigation should be conducted to identify the underlying reason and address the identified disparities within the landscape of corneal transplantation.
Comparing outcomes of balloon-expandable vs. self-expandable valves in transcatheter aortic valve replacement: a systematic review and meta-analysis
Authors: Khan Qaisar Ali , Farrukh Ameer Mustafa , Belay Naod F. , Li David , Afzal Muhammad , Nadella Adithya , Semakieh Bader , Baqi Abdul , Robles Rodríguez Alondra M. , Biougnach Meryem
Published: January 2024

Background:

Aortic stenosis (AS) is a common heart condition categorized into congenital and acquired forms. Transcatheter aortic valve replacement (TAVR) is an innovative method for AS management, and two valve types, self-expanding valves (SEV) and balloon-expandable valves (BEV), are used in TAVR. The objective of this study is to compare the clinical outcomes associated with balloon-expandable and self-expandable valves in transcatheter aortic valve replacement.

Methods:

The researchers conducted a comprehensive meta-analysis following PRISMA guidelines and AMSTAR-2 tool. The methodology involved a systematic literature search, strict eligibility criteria, unbiased study selection, meticulous data extraction, quality assessment, and rigorous statistical analysis.

Results:

Our analysis included twenty-six papers and 26 553 patients. BEV exhibited significant advantages over SEV in overall mortality across 21 studies, particularly in perioperative and 30-day assessments. However, no substantial disparities emerged between the two valve types in stroke incidence. BEV demonstrated notable benefits in reducing hospitalization rates across 6 studies and significantly fewer instances of permanent pacemaker implantations across 19 studies, particularly evident in the perioperative setting. Other secondary outcomes like bleeding, acute kidney injury, and myocardial infarction showcased non-significant differences between BEV and SEV.

Conclusion:

The analysis indicates that BEV may offer benefits in specific aspects of TAVR outcomes, but further research is needed to fully understand the factors influencing patient outcomes and mortality in TAVR procedures.
Comparison of 18F-FDG and 18F-FAPI PET/CT Findings of Signet-Ring Cell Carcinoma of the Stomach
Authors: Zhao Meixin , Zhang Annan , Zu Ming , Ma Yanpeng , Ding Shigang , Zhang Weifang
Published: January 2024

A 66-year-old man with gastric signet-ring cell carcinoma underwent both 18F-FDG and 18FAl-NOTA-FAPI PET/CT imaging. There was no abnormal FDG activity in the stomach, but there was diffuse intense 18FAl-NOTA-FAPI uptake in the known lesion and an adjacent metastasis.
Elevated 68Ga-FAPI Activity in Leiomyosarcoma
Authors: Wang Qixin , Zhou Yue , Chen XiaoLiang
Published: January 2024

Leiomyosarcoma is an aggressive subtype of soft tissue sarcoma with frequent metastatic relapse after curative surgery. Herein, we report the 68Ga-FAPI PET/CT findings in a 45-year-old woman with leiomyosarcoma. 68Ga-FAPI-04 PET/CT detected increased FAPI uptake in abdominal leiomyosarcoma and liver metastases. The positive findings of 68Ga-FAPI in this case highlighted that 68Ga-FAPI may have potential value in the evaluation of leiomyosarcoma.
Hemochromatosis Affects the Distribution of 68Ga-DOTATATE in the Liver and Spleen
Authors: Zhang Zeyu , Li Junhao , Zuo Changjing , Cheng Chao
Published: January 2024

Hemosiderosis is a chronic condition characterized by abnormal iron accumulation in tissues. In a PET scan of a 37-year-old woman, we observed an irregular distribution of 68Ga-DOTATATE in the liver and spleen. Specifically, 68Ga-DOTATATE appeared to be concentrated primarily in the peripheral regions of these organs, creating a distinctive “shell-like” appearance. This peculiar pattern may be attributed to the substantial accumulation of hemosiderin in the liver and spleen.
The Potential Utility of 18F-FDG PET/CT in Monitoring Corticosteroid Therapy in Inflammatory Pseudotumor
Authors: Sicilia Pozo María de las Nieves , García Zoghby Laura , López de la Osa García Aquilino , Sotillo Sánchez Ricardo , Poblete García Víctor Manuel
Published: January 2024

A 69-year-old man with suspected gastrointestinal stromal tumor was referred to 18F-FDG PET/CT. Images showed increased metabolism in a jejunal wall thickening, 2 liver lesions, and hepatic lymph nodes. The patient underwent wedge biopsy of the liver, which revealed inflammatory pseudotumor. The patient was treated with 20 mg/d prednisone, with a gradual dose reduction. A partial metabolic response was achieved after 2 months of therapy, and a final PET/CT showed complete metabolic response after 9 months. This clinical case shows the potential role of PET/CT in the assessment of the response of the inflammatory pseudotumor to corticosteroid therapy.
Urinary Endometriosis Misdiagnosed as Ureteral Malignant Tumor by PET/CT
Authors: Zhu Hao-Yu , Cheng You , Wang Si-Yun , Shao Dan
Published: January 2024

Endometriosis is a chronic inflammatory estrogen-dependent benign disease. It is defined as the endometrium growing outside the uterine cavity and the myometrium. It usually has low FDG uptake but rarely occurs in the ureters. We reported a case of a 47-year-old woman’s left ureteral nodule originally misdiagnosed as a ureteral malignant tumor by PET/CT and finally pathologically confirmed as endometriosis.
Gallbladder’s Adenocarcinoma With Enteroblastic Differentiation Revealed by 18F-FDG PET/CT
Authors: Cui Yan , Liu Yi , Du Bulin , Li Yaming , Li Xuena
Published: January 2024

Gallbladder’s adenocarcinoma with enteroblastic differentiation (GAED) is extremely rare. A 43-year-old woman complained of pain in the right upper abdomen, and enhanced CT showed a cystic and solid mixed mass in the hepatic hilar region. Adenocarcinoma with enteroblastic differentiation was pathologically identified. 18F-FDG PET/CT revealed a lesion in the gallbladder neck with increased FDG uptake, accompanied by a cystic and solid mixed mass in the hepatic hilar region with liver and lymph node metastases. Gallbladder biopsy was also carried out, and GAED was confirmed. 18F-FDG PET/CT may assist in the evaluation of GAED and guide biopsy.
Systematic analysis of the codon usage patterns of African swine fever virus genome coding sequences reveals its host adaptation phenotype
Authors: Wang Yuening , Chi Chenglin , Zhang Jiajia , Zhang Kaili , Deng Dafu , Zheng Wanglong , Chen Nanhua , Meurens François , Zhu Jianzhong
Published: January 2024

African swine fever (ASF) is a severe haemorrhagic disease caused by the African swine fever virus (ASFV), transmitted by ticks, resulting in high mortality among domestic pigs and wild boars. The global spread of ASFV poses significant economic threats to the swine industry. This study employs diverse analytical methods to explore ASFV’s evolution and host adaptation, focusing on codon usage patterns and associated factors. Utilizing phylogenetic analysis methods including neighbour-joining and maximum-likelihood, 64 ASFV strains were categorized into four clades. Codon usage bias (CUB) is modest in ASFV coding sequences. This research identifies multiple factors – such as nucleotide composition, mutational pressures, natural selection and geographical diversity – contributing to the formation of CUB in ASFV. Analysis of relative synonymous codon usage reveals CUB variations within clades and among ASFVs and their hosts. Both Codon Adaptation Index and Similarity Index analyses confirm that ASFV strains are highly adapted to soft ticks (Ornithodoros moubata) but less so to domestic pigs, which could be a result of the long-term co-evolution of ASFV with ticks. This study sheds light on the factors influencing ASFV’s codon usage and fitness dynamics, enriching our understanding of its evolution, adaptation and host interactions.
A Generalized Higher-order Correlation Analysis Framework for Multi-Omics Network Inference
Authors: Liu Weixuan , Pratte Katherine A. , Castaldi Peter J. , Hersh Craig , Bowler Russell P. , Banaei-Kashani Farnoush , Kechris Katerina J.
Published: January 2024

Multiple -omics (genomics, proteomics, etc.) profiles are commonly generated to gain insight into a disease or physiological system. Constructing multi-omics networks with respect to the trait(s) of interest provides an opportunity to understand relationships between molecular features but integration is challenging due to multiple data sets with high dimensionality. One approach is to use canonical correlation to integrate one or two omics types and a single trait of interest. However, these types of methods may be limited due to (1) not accounting for higher-order correlations existing among features, (2) computational inefficiency when extending to more than two omics data when using a penalty term-based sparsity method, and (3) lack of flexibility for focusing on specific correlations (e.g., omics-to-phenotype correlation versus omics-to-omics correlations). In this work, we have developed a novel multi-omics network analysis pipeline called Sparse Generalized Tensor Canonical Correlation Analysis Network Inference (SGTCCA-Net) that can effectively overcome these limitations. We also introduce an implementation to improve the summarization of networks for downstream analyses. Simulation and real-data experiments demonstrate the effectiveness of our novel method for inferring omics networks and features of interest.

Author summary

Multi-omics network inference is crucial for identifying disease-specific molecular interactions across various molecular profiles, which helps understand the biological processes related to disease etiology. Traditional multi-omics integration methods focus mainly on pairwise interactions by only considering two molecular profiles at a time. This approach overlooks the complex, higher-order correlations often present in multi-omics data, especially when analyzing more than two types of -omics data and phenotypes. Higher-order correlation, by definition, refers to the simultaneous relationships among more than two types of -omics data and phenotype, providing a more complex and complete understanding of the interactions in biological systems. Our research introduces Sparse Generalized Tensor Canonical Correlation Network Analysis (SGTCCA-Net), a novel framework that effectively utilizes both higher-order and lower-order correlations for multi-omics network inference. SGTCCA-Net is adaptable for exploring diverse correlation structures within multi-omics data and is able to construct complex multi-omics networks in a two-dimensional space. This method offers a comprehensive view of molecular feature interactions with respect to complex diseases. Our simulation studies and real data experiments validate SGTCCA-Net as a potent tool for biomarker identification and uncovering biological mechanisms associated with targeted diseases.
Phylogenetic and biogeographic history of the Snooks (Centropomidae: Carangiformes) spanning the closure of the Isthmus of Panama
Authors: Ossa-Hernández Natalia , Ballen Gustavo A. , Acero P. Arturo , Tavera Jose
Published: January 2024

Amphiamerican New World fishes provide a unique opportunity to explore the impact of geological processes and the formation of geographic barriers on biological diversification across both spatial and temporal dimensions. We employed phylogenetic and biogeographic methods to assess the impact of the emergence of the isthmus of Panama on the evolutionary history of Snooks. Bayesian methods were used for phylogenetic inference and divergence time estimation, incorporating the fossil record of Carangidae, Centropomidae, Istiophoriformes, Latidae, and Sphyraenidae to establish a timeline using methods of stratigraphic intervals. Biogeographic models were explored to test the hypothesis that trans-Isthmian vicariant events are coeval with the Isthmus closure. Our results suggest a sister relationship between Centropomidae and Sphyraenidae with a common ancestor that originated in the Upper Cretaceous (∼78.18 Ma). The biogeographic model DEC+jindicated within-area speciation and dispersal (founder effect) as the primary modes of speciation in the generaCentropomus,Lates,andSphyraena. The dispersion in the family Centropomidae was estimated from the Tropical Eastern Pacific to the Tropical Western Atlantic during the emergence of the isthmus of Panama. The alignment of divergence times with ancestral species distributions suggests a possible synchrony between the current distribution inCentropomusspecies and the gradual processes involved in the formation of the Isthmus of Panama during the Miocene. Furthermore, recent speciation events within each basin imply an influence of post-closure environmental conditions on the evolution of this group of fishes.