bluuebunny/crossref_metadata_2025_split huggingface dataset:
BUTYRATE-INDUCED MITOCHONDRIAL FUNCTION IMPROVES BARRIER FUNCTION IN INFLAMMATORY BOWEL DISEASE (IBD)
Authors: Conder Evan , Shay Henry C , Vekaria Hemendra , Erinkitola Iyabo , Bhogoju Sarayu , Goretsky Tatiana , Sullivan Patrick , Barrett Terrence , Kapur Neeraj 
Published: January 2023

Abstract

BACKGROUND
Short-chain fatty acids (SCFAs), end-product of gut microbial metabolism, play an important role in colonic homeostasis. Butyrate is a prime SCFA that fuels intestinal epithelial cells (IECs). However, this energy source is deficient in inflammatory bowel disease (IBD) due to dysbiotic microbiota. In this study, we posit that butyrate supplementation drives mitochondrial respiration induced barrier function in IBD.

METHODS
Normal human Colon mucosal (NCM460) epithelial cells were treated overnight with different concentration of sodium butyrate (SB; 0.5-5.0mM) with or without TNF (1ng/ml). To model mitochondrial deficiency, TFAM (mitochondrial transcriptional factor A), was silenced (shTFAM) in NCM460 cells. For mitochondrial respiration assessment, NCM cells were maintained and treated with SB (-/+TNF) under glucose-free medium and Oxygen consumption rate (OCR) was measured using high-throughput Seahorse XFe24 Extracellular Flux Analyzer (Agilent Technologies). Gene expression analysis was determined by RT-qPCR from total RNA isolated from untreated and treated NCM cells as well as in mitochondria-deficient shTFAM NCMs compared to shControl cells. All assays were performed in triplicate and fold changes were calculated using the ΔΔCT method.

RESULT
Seahorse analysis showed significant increase in Maximal respiratory capacity, spare respiratory capacity and ATP production at sub-optimal (2mM) and optimal (5mM) SB concentrations, suggesting a SB induced mitochondrial respiration and capacity to overcome oxidative stress. At molecular level, SB significantly increased the expression of genes associated with mitochondrial biogenesis (TFAM), complex I (Ndufa1, Ndufa4, Ndufa6), complex IV (Cox6A1) and complex V (ATP5E, ATP8), at optimal 5mM concentration. The effect of SB was more pronounced under inflammatory condition when NCM cells were treated in the presence of low dose TNF. Further transcriptomic analysis of TFAM-deficient NCMs demonstrated significant decrease in mRNA of major butyrate transporters (MCT1, MCT4, ABCG2) compared to TFAM-proficient shControl cells, irrespective of any treatment. Similar decreased expression pattern was observed for tight junction genes (ZO1 and Occludin) in shTFAM compared to shControl cells. However, butyrate transporters and ZO1 mRNA increased significantly in both shTFAM and shControl cells after SB treatment at sub-optimal concentration (2mM) in the presence of TNF. Interestingly, only shTFAM cells showed increase in transcript level of Occludin after SB+TNF treatment, with no effect in shControl.

CONCLUSION
These data suggest that butyrate metabolism is a critical player in promoting oxidative health of mitochondria, which further drives transporter-mediated butyrate utilization and promotes barrier integrity under inflammatory conditions as in IBD.
THE BENEFICIAL ROLE OF PROBIOTIC AKKERMANSIA MUCINIPHILA IN INFLAMMATORY BOWEL DISEASE
Authors: Zheng Mengyu , Han Ran , Yuan Yali , Xing Yunqi , Zhang Wenji , Liu Yuyue , Li Junxiang , Mao Tangyou 
Published: January 2023

Abstract
Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, is a chronic relapsing gastrointestinal inflammatory disease mediated by dysregulated immune responses to resident intestinal microbiota. Current conventional approaches including aminosalicylates, corticosteroids, immunosuppressive agents, and biological therapies are focused on reducing intestinal inflammation besides inducing and maintaining disease remission, and managing complications. However, these therapies are not curative and are associated with various limitations, such as drug resistance, low responsiveness and adverse events. Recent accumulated evidence has revealed the involvement of mucin-degrading bacterium Akkermansia muciniphila (A. muciniphila) in the regulation of host barrier function and immune response. Although the role of commensal A. muciniphila in IBD is controversial and needs further investigations, most clinical and experimental results still support the protective effect of A. muciniphila in the process and development of intestinal inflammation. Therefore, A. muciniphila-targeted and -based therapies is now considered a valuable therapeutic approach to treat IBD patients. However, how to selectively enrich the growth and colonization of A. muciniphila in the host intestine with direct or indirect interventions have not been clarified. This review reveals an interesting phenomenon that not only viable A. muciniphila, but pasteurised A. muciniphila, and its ingredients such as AmEVs, Amuc_1100 and P9 also can alleviate intestinal inflammation, suggesting a therapeutic potential of A. muciniphila in the treatment of IBD. More importantly, because of the natural characteristics individual strains grow, we believe that it is more promising weapon for the treatment of IBD to improve the intestinal microenvironment of A. muciniphila than to simply increase the number of individual bacteria itself. Therefore, it has become a research hotspot in recent years to improve intestinal microenvironment and indirectly promote the colonization of A. muciniphila through the supplementation of other probiotic or prebiotics, natural diets, drugs, and herbs, and achieved good progress, holds promise for A. muciniphila-targeted and -based therapies in the treatment of IBD.
THE GUT MICROBIOME REGULATES EFFICACY OF SULFASALAZINE THERAPY FOR SPONDYLOARTHRITIS IN INFLAMMATORY BOWEL DISEASE
Authors: Lima Svetlana , Rupert Amanda , Jin Wenbing , Viladomiu Monica , Pires Silvia , Woo Viola , Putzel Gregory , Marderstein Andrew , Funez-dePagnier1 Gabriela , Yang Wei , Guo Chun-Jun , Scherl Ellen , Longman Randy 
Published: January 2023

Abstract
Joint inflammation, or spondyloarthritis (SpA), is the most common extra-intestinal manifestation of inflammatory bowel disease (IBD), but the specific role for therapies targeting SpA is not well defined. One of the earliest medications used for the treatment of IBD is sulfasalazine (SAS). SAS is a prodrug composed of two chemical moieties, the anti-inflammatory 5-aminosalicilate and the antibiotic sulfapyridine. The efficacy of SAS in peripheral arthritis is thought to depend on its “antibacterial” properties, however the impact of SAS on the IBD-SpA microbiome and how it may improve extra-intestinal symptoms is unknown. Therefore, our study aims to diagnostically evaluate the role for the fecal microbiome in clinical response to SAS therapy and identify microbial and immunologic therapeutic targets associated with clinical response.
We have designed an observational study to longitudinally follow IBD patients with SpA who have a medical indication for SAS therapy. Clinical data and fecal samples from 22 patients were collected before initiation of SAS and at week 12 after initiation of SAS. Eleven IBD-SpA patients were concomitantly enrolled as controls and followed by 12 weeks. Metagenomic sequencing was used to define the effect of SAS on the IBD-SpA fecal microbiome and to evaluate its relationship with improvement in joint symptoms. Mouse models and in vitro assays were used to test the sufficiency of the SAS effect observed in patients.
The fecal microbiome of SAS-responders was distinct from that observed in non-responders and 6 pre-treatment microbial markers (including the short chain fatty acid (SCFA) producer Faecalibacterium prausnitzii) predicted SAS-response (AUC = 0.9). Fecal metabolome of SAS responders had lower thymine and higher deoxyuridine compared to non-responders consistent with evidence of a folate trap in response to SAS treatment. SAS therapy in SPF mouse-model of chemically-induced colitis alleviated colitis in GPR 109a-dependent fashion consistent with a synergistic role for SCFA. In vitro assays revealed SAS direct regulation of F. prausnitzii metabolic function and butyrate synthesis.
CONCLUSIONS: Collectively, these findings highlight the potential role for microbial diagnostics to improve SAS efficacy, and drug modulation of microbial markers to potentiate therapy for IBD patients with SpA.
ESTABLISHMENT AND TREATMENT OF MURINE COLONOIDS TO STUDY THE EPITHELIAL EFFECTS OF INTESTINAL INFLAMMATION IN VITRO
Authors: Crawford Erin , Mentrup Heather , Novak Elizabeth , Mollen Kevin 
Published: January 2023

Abstract

BACKGROUND
Disruption of the intestinal epithelial barrier is a hallmark of inflammatory bowel disease (IBD). The 3-dimensional colonoid culture system is a useful in vitro model to study intestinal stem cell dynamics and epithelial cell physiology in IBD pathogenesis. However, we have shown that in vivo epithelial changes are not necessarily retained in colonoids established from mice undergoing acute inflammation using a DSS model and primarily reflect stem cell physiology rather than that of terminally differentiated cells. We developed experimental methods to address this limitation. We terminally differentiate colonoids or create 2-D monolayers, and challenge them with a cocktail of inflammatory mediators that are typically elevated during IBD.

METHODS
Murine colonoids are established by isolating colonic crypts and plating them in basement membrane matrix. Over 3 to 5 days, crypt structures develop into spheroid colonoids 250 μm in diameter, forming a prominent lumen surrounded by a thin layer of epithelial stem cells. They are passaged a minimum of two times and then are either 1) terminally differentiated by incubating the colonoids with Differentiating Media or 2) used to establish intestinal epithelial monolayers. Inflammation is then induced by incubating cells with a cocktail of inflammatory mediators (TNFa, IL-1b, IFNg, H2O2). Protein is collected after 72 hours, and expression of proteins involved in mitochondrial biogenesis were assessed (n=3).

RESULTS
We found that changes in mitochondrial dynamics, reflective of key metabolic changes in the epithelium that are observed in colonic scrapings of DSS-treated mice are not recapitulated in traditional colonoids derived from mice on the same DSS regimen. We found that changes in expression and protein levels of peroxisome proliferator-activator receptor-gamma coactivator-1a (PGC1a), the master regulator protein of mitochondrial biogenesis, were not maintained in colonoids. After terminally differentiating colonoids and subsequently inducing inflammation, we were able to recapitulate a failure of mitochondrial biogenesis failure that is a hallmark of both human IBD and murine colitis. Protein expression of PGC1a as well as downstream transcription factor A, mitochondria (TFAM) were both decreased when assessed via western blot.

DISCUSSION
Colonoids are a useful tool for studying colonic physiology in vitro, however are limited in their ability to evaluate the effects of in vivo inflammation on the mitochondrial function and cellular metabolism. When removed from the intestinal milieu, crypt cells demonstrate a recovery of mitochondrial health and reflect stem primarily stem cell physiology. Our strategies provide opportunities for organoid manipulation which, when employed properly, can shed light on key aspects of intestinal epithelial mitochondrial function during inflammation.
THE EFFECT OF VEDOLIZUMAB ON CD8 T CELL REPERTOIRE HOMOGENEITY AND BLOOD-GUT TRAFFICKING IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Williams Kyle , Shows Donna , Kongala Ramya , Hindmarch Duncan , Clarke Astrid , Lord James 
Published: January 2023

Abstract

BACKGROUND
Inflammatory bowel disease (IBD) causes T cell infiltration of the intestinal mucosa, but the heterogeneity of these cells is not understood at a clonal level. The drug vedolizumab is believed to treat IBD by blocking the entry of circulating integrin α4β7+ T cells into the intestinal mucosa.

METHODS
We sought to understand the clonal distribution of T cells in IBD and how this is affected by vedolizumab by studying the T cell receptor (TCR) repertoire in CD8+ T cell subsets sorted from blood samples and colon mucosal biopsies via FACS. Inflamed or uninflamed colon segments from 15 ulcerative colitis and 13 Crohn’s disease patients were compared to colon biopsies from 11 people without IBD. In peripheral blood, we profiled purified α4β7+, α4β7- effector/memory, CD45RA+ terminal effector/memory (TEMRA) CD8 T cells, and mucosal-associated invariant T (MAIT) cells. In a separate cohort of 13 IBD patients, samples were obtained before and during vedolizumab therapy to determine its effect on the diversity and overlap of the TCR repertoires of blood and colon CD8+ T cells.

RESULTS
CD8 TCR diversity in the mucosa and peripheral blood did not correlate with inflammation. Repertoire overlap between any two anatomically distinct locations of a person’s colon was consistently high, though often lower between inflamed and uninflamed sites. CD8 TCR repertoire overlap was also seen between the colon and each peripheral blood subpopulation studied, with the highest overlap seen for integrin α4β7+ T cells and the lowest for MAIT cells. Inflamed tissue overlapped more than uninflamed with each blood subpopulation. Surprisingly, vedolizumab did not affect the degree of overlap between colon CD8+ T cells and circulating α4β7+ CD8 T cells, nor their TCR diversity, regardless of treatment efficacy. Indeed, flow cytometry revealed no relative depletion of effector/memory T cells in the colons of vedolizumab recipients. Instead, vedolizumab caused the depletion of rare naïve mucosal T cells and dendritic cells (DC) from the colonic mucosa.

CONCLUSIONS
CD8 T cell clones are spread homogenously throughout the colon. Although TCR repertoire overlap is greater within than between inflamed and uninflamed colon segments, a similar diversity of TCRs in both argues against local clonal expansion being the main source of excess T cells in inflamed mucosa. Rather, our data reveal increased TCR overlap between blood and inflamed mucosa to support the significance of T cell trafficking in IBD pathogenesis, particularly concerning experienced α4β7+ T cell populations. However, we surprisingly found neither gross nor clonal evidence that blockade of this trafficking is the mechanism by which vedolizumab treats IBD, instead finding only naïve T cells and DC to be depleted from the colonic mucosa in response to vedolizumab.
Analytical and Biological Variability of a Commercial Modified Aptamer Assay in Plasma Samples of Patients with Chronic Kidney Disease
Authors: Dubin Ruth F , Deo Rajat , Ren Yue , Lee Hongzhe , Shou Haochang , Feldman Harold , Kimmel Paul , Waikar Sushrut S , Rhee Eugene P , Tin Adrienne , Chen Jingsha , Coresh Joseph , Go Alan S , Kelly Tanika , Rao Paduranga S , Chen Teresa K , Segal Mark R , Ganz Peter 
Published: January 2023

Abstract

Background
We carried out a study of the aptamer proteomic assay, SomaScan V4, to evaluate the analytical and biological variability of the assay in plasma samples of patients with moderate to severe chronic kidney disease (CKD).

Methods
Plasma samples were selected from 2 sources: (a) 24 participants from the Chronic Renal Insufficiency Cohort (CRIC) and (b) 49 patients from the Brigham and Women’s Hospital–Kidney/Renal Clinic. We calculated intra-assay variability from both sources and examined short-term biological variability in samples from the Brigham clinic. We also measured correlations of aptamer measurements with traditional biomarker assays.

Results
A total of 4656 unique proteins (4849 total aptamer measures) were analyzed in all samples. Median (interquartile range [IQR] intra-assay CV) was 3.7% (2.8–5.3) in CRIC and 5.0% (3.8–7.0) in Brigham samples. Median (IQR) biological CV among Brigham samples drawn from one individual on 2 occasions separated by median (IQR) 7 (4–14) days was 8.7% (6.2–14). CVs were independent of CKD stage, diabetes, or albuminuria but were higher in patients with systemic lupus erythematosus. Rho correlations between aptamer and traditional assays for biomarkers of interest were cystatin C = 0.942, kidney injury model-1 = 0.905, fibroblast growth factor-23 = 0.541, tumor necrosis factor receptors 1 = 0.781 and 2 = 0.843, P &lt; 10−100 for all.

Conclusions
Intra-assay and within-subject variability for SomaScan in the CKD setting was low and similar to assay variability reported from individuals without CKD. Intra-assay precision was excellent whether samples were collected in an optimal research protocol, as were CRIC samples, or in the clinical setting, as were the Brigham samples.
Intradural extramedullary meningeal melanocytoma: a case report and literature review
Authors: Parwez Rabeeia , Ahmed Razna , Baig Arsalan , Ruiz Fernanda , Baig Mirza Asfand , Sadek Ahmed-Ramadan , Arvin Babak , Qureshi Anjum 
Published: January 2023

Abstract
Primary meningeal melanocytomas are extremely rare, benign tumours arising from the leptomeninges. While they are considered to be benign lesions, there is potential for their growth and transformation into malignant melanomas. They are commonly found in the cervical spine, with a decreased incidence in the thoracic and lumbar regions. We present a case report of a 56-year-old man who presented to our unit with a 4-month history of lower limb weakness and a sensory level at T6. Magnetic resonance imaging shows an intradural extramedullary tumour. The patient underwent a thoracic debulking of the lesion with neurophysiological monitoring. Histopathology confirmed the diagnosis of melanocytoma of meningeal origin, with a low mitotic count. Our patient recovered well post-operatively with no complications. Surgical resection is an effective method to manage this tumour; however, adjuvant radiotherapy is advised due to the risk of recurrence and malignant transformation.
Developing and Sustaining a Culturally Responsive and Positive School Climate
Authors: Goforth Anisa N. , Pham Andy V. 
Published: January 2023

Abstract
This chapter provides an overview of school climate, which is defined broadly as the students’, teachers’, and staff’s feelings, attitudes, and experiences of their school life. Further, there are a number of dimensions of school climate, including safety, relationships (student–student as well as student–teacher), teaching and learning, institutional environment, school improvement, and social media. Next, one specific framework, the cultural-ecological model of school climate, is introduced, which can be helpful in developing and sustaining a safe and positive school climate. Mental health professionals should take the lead in developing, adapting, and delivering effective violence prevention and intervention programs based on data to ensure that they make a difference in developing a positive school climate and promoting safety. School climate data can also contribute to the development of refined policies to that ensure procedures, processes, and positive outcomes are sustained.
Culturally Responsive Multi-Tiered Systems of Support and Evidence-Based Interventions
Authors: Goforth Anisa N. , Pham Andy V. 
Published: January 2023

Abstract
Schools have repeatedly struggled to address racial or ethnic disproportionality, particularly related to overrepresentation in exclusionary discipline practices and identification for special education services. Culturally responsive approaches in the provision of academic and behavior supports can increase student belonging and improve student outcomes in schools. This chapter discusses cultural issues when delivering instructional and behavioral supports using a multi-tiered system of support, including pedagogical considerations. Schools are responsible for implementing culturally responsive evidence-based interventions, supporting knowledge and skills for professional educator and staff behavior, and fostering culturally valid data-based decision-making, with the goal of attaining equitable academic, social, and behavioral outcomes. Recommendations are provided for adapting and evaluating effectiveness of interventions for those students who need additional individualized support.
Counseling and Psychotherapy to Support Diverse Students
Authors: Goforth Anisa N. , Pham Andy V. 
Published: January 2023

Abstract
This chapter presents an overview of the culturally responsive approaches to providing counseling and psychotherapy to culturally and linguistically diverse students. Practitioners should consider the ecological perspectives of mental health and well-being. In particular, they should ensure that the counseling is from a strengths-based, and not deficit-based, perspective. Practitioners should (1) engage in critical reflexivity of their knowledge and skills, (2) build relationships, develop goals, and create a culturally affirming space, (3) consider the salient sociocultural factors and cultural dimensions that may be relevant in the case, (4) examine how to incorporate sociocultural factors or cultural dimensions into the counseling, (5) review the potential counseling approaches and understand the cultural assumptions of each, and (6) implement the treatment using cultural strengths. Finally, the chapter highlights some key professional, ethical, and legal considerations for providing counseling to culturally and linguistically diverse students.
Engaging With Couples
Authors: Starks Tyrel J. 
Published: January 2023

AbstractThis chapter reviews concepts and novel skills uniquely relevant to establishing rapport and a working alliance with couples. The concept of relational orientation is reviewed along with its implications for considering the use of first-, second-, and third-person pronouns in session dialogue. Factors unique to understanding the social context in which couples are embedded (e.g., social network overlap, couple-level discrimination, and relationship marginalization) are also discussed. The task of balancing attention along the dialectic of focus—shifting between attending to the individual partners and the couple as a whole—is demonstrated. Following this, the use of opening statements to establish norms in couples Motivational Interviewing as well as new active listening skills—dyadic reflections and relationship affirmations—are introduced, and their function in session is reviewed.
Facilitating Dyadic Functioning
Authors: Starks Tyrel J. 
Published: January 2023

AbstractThis chapter introduces the novel process of facilitating dyadic functioning to the traditional four-process Motivational Interviewing framework. Like all Motivational Interviewing processes, facilitating is relevant throughout the course of treatment; however, it emerges prototypically as most salient after the initial engaging process, and some attention to facilitating is warranted to prepare the couple before focusing on the target behavior moves to the foreground. The chapter begins with an overview of research linking relationship functioning to physical and mental health. Common approaches to conceptualizing key domains of relationship functioning (including satisfaction, commitment, and emotional investment) are reviewed before discussing how these domains might emerge in a Motivational Interview with a couple. Finally, strategies for facilitating dyadic functioning in couples Motivational Interviewing are discussed.