bluuebunny/crossref_metadata_2025_split huggingface dataset:
MUCOSAL EXPRESSION OF GENES PI3, ANXA1, AND VDR DESCRIMINATES CROHNS DISEASE FROM ULCERATIVE COLITIS IN INFLAMMATORY BOWEL DISEASE PATIENTS
Authors: James Jaslin , Nielsen Boye S , Christensen Ib , Langholz Ebbe , Malham Mikkel , Riis Lene , Høgdall Estrid 
Published: January 2023

Abstract

INTRODUCTION
Differential diagnosis of Inflammatory Bowel Disease Unclassified (IBDU) patients to Crohn’s Disease (CD) or Ulcerative Colitis (UC) at diagnosis is challenging. Personalized disease-specific strategies are becoming state of art and therefore it is of importance for outcome of the patients and treatment decision to be taken by the clinicians to have a precise diagnosis.

METHODS
Whole transcriptome RNA sequencing was performed using AmpliSeq human gene expression panel on formalin-fixed paraffin-embedded (FFPE) colonic mucosal biopsies of IBD patients (CD, n=16, UC, n=17) and non-IBD controls (n=10) to study differential gene expression between CD and UC samples. Top 100 of the most significant differentially expressed genes were then tested in two independent external GEO datasets. Functional enrichment analysis of 10 successful candidates were performed and 7 genes were selected for further validation. RT-qPCR analyses were performed on an independent patient cohort of 45 CDs and 53 UCs along with 12 non-IBD controls. The cDNA samples were submitted to quality restriction during the statistical analysis resulting in a cut-off of Ct values below 29 for the endogenous control allowing 46 patient samples to enter the analysis. In situ hybridization (ISH) was performed using RNAscope on 11 selected cases for describing tissue localisation and expression.

RESULTS
Sequencing results showed 308 genes differentially expressed between CD and UC from a total of 14190 genes. The genes MTCL1, SH3PXD2A-AS1, CLCF1, and CD180 were under the limit of detection with RT-qPCR and were excluded from further analysis. Relative expression levels from RT-qPCR for the genes PI3, ANXA1, and VDR, together with the age and sex, resulted in an area under the receiver-operating characteristic curve (AUC) of 0.84 (P = 0.02) in discriminating CD from UC. Significantly higher expression of VDR alone was observed in CD samples with AUCs of 0.77 (P = 0.01). ISH analyses showed expression of PI3, ANXA1, and VDR mRNAs localized to mucosal epithelial cells.

CONCLUSION
Using whole transcriptome analysis of FFPE sample-derived RNA, we have identified genes that are differentially expressed in CD and UC, and we have developed an RT-qPCR assay including a panel of 3 genes (PI3, ANXA1, VDR) for the differential diagnosis among IBD unclassified (IBDU) patients. We propose that the RT-qPCR assay could be used in a clinical routine setup for distinguishing UC from CD.
REAL WORLD IMPLEMENTATION OF TREAT-TO-TARGET IN PATIENTS WITH IBD IN A LEARNING HEALTH SYSTEM: AN IBD QORUS COLLABORATIVE STUDY
Authors: Singh Siddharth , Oliver Brant , Hou Jason , Lum Donald , van Deen Welmoed , Weaver Alandra , Siegel Corey , Melmed Gil 
Published: January 2023

Abstract

BACKGROUND AND AIMS
A treat-to-target (TTT) strategy of aiming for symptomatic and endoscopic remission is recommended for the management of inflammatory bowel diseases (IBD). Yet, real-world uptake of TTT strategies has been modest. We sought to assess the feasibility of implementing TTT and improve its uptake in the Crohn’s and Colitis Foundation’s IBD Qorus learning health system (LHS).

METHODS
We examined an ‘intention to TTT’ for each eligible clinic visit (patients not in endoscopic remission on most recent evaluation) across a multi-center LHS over a 12-month period (November 2020-November 2021). ‘Intention to TTT’ (or TTT score) was defined as an affirmative response to all three of the following: (1) Was treat-to target discussed with patient?, (2) Was objective assessment for inflammation (endoscopy, radiology and/or fecal calprotectin) performed within the preceding 12m?, (3) Is there an intention to change treatment since target has not been reached? Over a 12-month breakthrough series (BTS) collaborative, we sought to improve implementation of TTT with monthly report cards, webinars, an active listserv and two all-Qorus learning sessions. Changes in rates of ‘intention to TTT’ were examined over 12 months, overall and at each site, with an earliest clinically meaningful signal of improvement defined a priori as 2% increase per month. In secondary analyses, we compared overall rates of achieving endoscopic remission and corticosteroid-free clinical remission in sites with improvement in rates of ‘intention to TTT’ relative to sites without improvement (only sites with valid data for 8/12 months).

RESULTS
Over 12 months, there were 7934 patient visits across 38 sites in the collaborative; patients in 37% visits (n=2913) were not in endoscopic remission at time of visit. Overall, rates of ‘intention to TTT’ increased from 23% at the beginning of the BTS, to 49% at the end of the BTS, corresponding to a clinically significant 2.4% per month increase in rates of implementing TTT (Figure 1). While rates of discussion of TTT (88% of eligible visits) and intending to adjust therapy (70% of eligible visits) were consistently high, there was a significant increase in objective evaluation for inflammation during the course of the BTS. There was considerable variability across sites in rates of ‘intention to TTT’. Comparing 9/14 sites with improvement in rates of implementing TTT vs. 5/14 sites without improvement, there were trends towards increasing rates of site-level endoscopic remission and steroid-free clinical remission (Figure 2).

CONCLUSIONS
Through a quality improvement initiative in a LHS, rates of ‘intention to TTT’ increased significantly over 12-months. This improvement in implementation of TTT was accompanied by increase in rates of achieving endoscopic remission and steroid-free clinical remission.
Age-related alterations in protein phosphatase 2A methylation levels in brains of cynomolgus monkeys: a pilot study
Authors: Ando Sana , Sakurai Masashi , Shibutani Shusaku , Kimura Nobuyuki , Shimozawa Nobuhiro , Yasutomi Yasuhiro , Yabe Ryotaro , Ohama Takashi , Sato Koichi 
Published: January 2023

Abstract
The abnormal activity of PP2A, a dominant member of type 2A serine/threonine protein phosphatase, has been implicated in the development of Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). PP2A is a holoenzyme, and protein methylation of the catalytic subunit, PP2Ac, alters the complex composition. A decrease in PP2Ac methylation levels has been reported in AD and DLB. Aging is the most common risk factor for AD and DLB, but the relationship between aging and PP2A has not been studied in detail. Cynomolgus monkey show increased phosphorylation levels of tau and α-synuclein with aging. In this study, we investigated the alterations in the PP2A activity regulation with aging in monkey brains from 2 to 43 years of age using fractionated proteins. We found that type 2A protein phosphatase activity decreased with aging in cytoplasmic and nuclear-soluble fractions. PP2Ac methylation level was decreased in cytoplasmic and sarkosyl-insoluble fractions. A principal component analysis using PP2Ac, demethylated PP2Ac and PP2A methylesterase PME-1 levels in cytoplasmic and nuclear-soluble fractions as attributes showed that aged monkeys were in the same cluster. Our results show that brain aging in cynomolgus monkeys is closely related to changes in PP2A methylation.
Elevated levels of circulatory follicular T helper cells in chronic lymphocytic leukemia contribute to B cell expansion
Authors: Le Saos-Patrinos Corentin , Loizon Séverine , Zouine Atika , Turpin Delphine , Dilhuydy Marie-Sarah , Blanco Patrick , Sisirak Vanja , Forcade Edouard , Duluc Dorothée 
Published: January 2023

AbstractChronic lymphocytic leukemia (CLL) is characterized by an expansion of mature B cells in the bone marrow, peripheral lymphoid organs, and blood. CD4 T helper (Th) lymphocytes significantly contribute to the physiopathology of CLL, but the subset(s) of Th cell involved in CLL pathogenesis is (are) still under debate. In this study, we performed flow cytometry analysis of the circulatory T cells of untreated CLL patients and observed an increase in follicular helper T cells (Tfh), which is a subset of T cells specialized in B cell help. Elevated numbers of Tfh cells correlated with disease severity as measured by the Binet staging system. Tfh from CLL patients were activated and skewed toward a Th1 profile as evidenced by their PD-1+IL-21+IFNγ+ phenotype and their CXCR3+CCR6− chemokine receptor profile. Tfh efficiently enhanced B-CLL survival and proliferation through IL-21 but independently of IFNγ. Finally, we observed an inverse correlation between the Tfh1 and IgA and IgG serum levels in patients, suggesting a role for this Tfh subset in the immune dysfunction associated with CLL. Altogether, our data highlight an impairment in circulatory Tfh subsets in CLL patients and their critical role in CLL physiopathology.
Children and adolescents in the Amsterdam Cohort of Gender Dysphoria: trends in diagnostic- and treatment trajectories during the first 20 years of the Dutch Protocol
Authors: van der Loos Maria A T C , Klink Daniel T , Hannema Sabine E , Bruinsma Sjoerdje , Steensma Thomas D , Kreukels Baudewijntje P C , Cohen-Kettenis Peggy T , de Vries Annelou L C , den Heijer Martin , Wiepjes Chantal M 
Published: January 2023

AbstractBackgroundTwenty years ago, the Dutch Protocol—consisting of a gonadotropin-releasing hormone agonist (GnRHa) to halt puberty and subsequent gender-affirming hormones (GAHs)—was implemented to treat adolescents with gender dysphoria.AimTo study trends in trajectories in children and adolescents who were referred for evaluation of gender dysphoria and/or treated following the Dutch Protocol.MethodsThe current study is based on a retrospective cohort of 1766 children and adolescents in the Amsterdam Cohort of Gender Dysphoria.OutcomesOutcomes included trends in number of intakes, ratio of assigned sex at birth, age at intake, age at start of GnRHa and GAH, puberty stage at start of GnRHa, proportions of adolescents starting and stopping GnRHa, reasons for refraining from GnRHa, and proportions of people undergoing gender-affirming surgery.ResultsA steep increase in referrals was observed over the years. A change in the AMAB:AFAB ratio (assigned male at birth to assigned female at birth) was seen over time, tipping the balance toward AFAB. Age at intake and at start of GnRHa has increased over time. Of possibly eligible adolescents who had their first visit before age 10 years, nearly half started GnRHa vs around two-thirds who had their first visit at or after age 10 years. The proportion starting GnRHa rose only for those first visiting before age 10. Puberty stage at start of GnRHa fluctuated over time. Absence of gender dysphoria diagnosis was the main reason for not starting GnRHa. Very few stopped GnRHa (1.4%), mostly because of remission of gender dysphoria. Age at start of GAH has increased mainly in the most recent years. When a change in law was made in July 2014 no longer requiring gonadectomy to change legal sex, percentages of people undergoing gonadectomy decreased in AMAB and AFAB.Clinical ImplicationsA substantial number of adolescents did not start medical treatment. In the ones who did, risk for retransitioning was very low, providing ongoing support for medical interventions in comprehensively assessed gender diverse adolescents.Strengths and LimitationsImportant topics on transgender health care for children and adolescents were studied in a large cohort over an unprecedented time span, limited by the retrospective design.ConclusionTrajectories in diagnostic evaluation and medical treatment in children and adolescents referred for gender dysphoria are diverse. Initiating medical treatment and need for surgical procedures depends on not only personal characteristics but societal and legal factors as well.
Antimicrobial, antiadhesive, and antibiofilm actions of rhamnolipids on ESKAPE pathogens
Authors: Firdose Ayesha , Chong Nur Hazlin Hazrin , Ramli Ramliza , Aqma Wan Syaidatul 
Published: January 2023

Abstract
The aim of this study was to test the antimicrobial, antiadhesive, and antibiofilm activities of a rhamnolipid extracted from Pseudomonas aeruginosa UKMP14T previously isolated from oil-contaminated soil in Malaysia against ESKAPE (i.e. multidrug resistant) pathogens. Zones of inhibition in an agar well diffusion assay were observed at 50 µg mL−1 concentrations of rhamnolipid for all the ESKAPE bacteria. The MIC and MBC values ranged between 7.81–62.5 µg mL−1 and 31.25–1000 µg mL−1, respectively. Percent killing was recorded to be &gt;90% except for Klebsiella pneumoniae (86.84%). Furthermore, antiadhesion studies showed that there was 76% hindrance in attachment of Enterococcus faecium and 91% in Acinetobacter baumannii at 4 × MIC. The highest inhibition in adhesion was found at 4 × MIC, which was 46% for Ac. baumannii and 62% for Enterococcus faecium. Finally, the antibiofilm capability of the rhamnolipid was determined, which ranged between 25%–76% in Ac. baumannii and 35%–88% in Enterococcus faecium. To the best of our knowledge, this is the first study to include research on antimicrobial, antiadhesive and antibiofilm activities of rhamnolipid from the local isolate Ps. aeruginosa UKMP14T against ESKAPE bacteria. Obtained results suggest that this rhamnolipid can be exploited commercially for the production of novel antibiotics.
Culturally Responsive Approaches to Traditional Assessment
Authors: Goforth Anisa N. , Pham Andy V. 
Published: January 2023

Abstract
This chapter describes strategies for conducting culturally responsive assessments that foster collaboration with families to develop goals and school-based supports for students. The Culturally Responsive Strengths-Based Assessment to Inform Intervention includes five steps: (1) relationship building and goal orientation, (2) assessment of sociocultural and ecological factors that foster resilience, (3) collaborative development of an intervention aligned toward a goal, (4) implementing an intervention, and (5) evaluating strengths within an intervention and areas to improve. The most comprehensive approach to assessing sociocultural and ecological factors is through a multi-method and multi-source approach. Specifically, practitioners can gather information from (1) reviewing psychological, educational, and medical records, (2) school and home observations, (3) interviews, and (4) tests and measures. Finally, this chapter briefly provides suggestions for summarizing and synthesizing this information in a written report and sharing the results with the student and their caregivers.
Literacy, Language, and Acculturation of Diverse Students
Authors: Goforth Anisa N. , Pham Andy V. 
Published: January 2023

Abstract
Culturally and linguistically diverse (CLD) students often enter a new classroom bringing their own educational and family history, language background, and life experiences. The purpose of this chapter is to discuss best practices in conducting ecological assessment of academic learning and language of CLD students. In particular, the chapter discusses how enculturation, assimilation, and acculturation contribute to student’s learning and language development. These processes can also affect how students approach classwork and assessment tasks. Achievement and opportunity gaps are often the outcomes when curricula, instruction, and assessment do not capture the cultural strengths of students. Recommendations are provided for educators and practitioners to assess and address literacy and language skills of CLD students better, including English language learners.
Assessing Intelligence of Diverse Students
Authors: Goforth Anisa N. , Pham Andy V. 
Published: January 2023

Abstract
Psychological testing and assessment of intelligence have been fraught with controversy, particularly when it comes to evaluation of culturally and linguistically diverse students. Cultural bias in intelligence tests is thought to be the reason for disproportionate placement in special education or gifted education programs. The chapter discusses the issues and complexities regarding the construct of intelligence, measurement of intelligence, and their use in educational decision-making. Although intelligence tests will likely continue to be widespread in school systems, norm-referenced interpretations do not necessarily provide contextual information on individual learning strengths and weaknesses. The chapter provides recommendations for more contextualized assessment of intelligence, which can help mitigate the challenges for using standardized tests of intelligence in schools.
Discussing Sex as Both a Goal and Context
Authors: Dellucci Trey V. , Starks Tyrel J. 
Published: January 2023

AbstractFor a range of reasons, the integration of attention to sex and sexuality may enhance Motivational Interviewing practice. Goals related to sexual satisfaction or improving sexual health may motivate some clients to pursue counseling. For some clients, substance use and sex are highly interrelated behaviors, making sex essential to any understanding of factors motivating substance use. This chapter provides an overview of information about normative sexuality development and functioning that is essential for counselors who wish to integrate attention to sex in their practice. We review the historical separation of sex therapy from counseling more generally and provide examples of how Motivational Interviewing counselors might draw upon models from couples’ HIV testing and counseling (CHTC), sensate focus therapy, and sexual script research to integrate attention to couples’ sexual satisfaction and sexual risk reduction in Motivational Interviewing practice.
Session 3: Increasing Motivation for Treatment Through Values
Authors: Woods Douglas W. , Twohig Michael P. 
Published: January 2023

Abstract
This chapter discusses how to increase the patient’s motivation for treatment by uncovering their values. Therapy aims to help the patient lead a better life instead of just reducing hair-pulling habits. Values refer to the kind of person the patient wants to be. Values differ from goals, which are short-term and can be achieved. Therapy and following one’s values lie in the process instead of the outcome. Values serve as a guiding light that can be constantly and continually worked toward. Worksheets help the patient determine the life they want to live. These are used to explore the patient’s values and motivate them to work on reducing hair-pulling habits.
Session 4: Can Pulling-Related Inner Experiences Be Controlled?
Authors: Woods Douglas W. , Twohig Michael P. 
Published: January 2023

Abstract
This chapter explores the strategies patients can use to control pulling urges while also regulating their internal experiences. It highlights the importance of values, which help provide motivation for the work the patient is putting into improving their life. The therapist encourages the patient to talk about the strategies they use to try to control urges to pull or other unpleasant internal experiences such as thoughts, emotions, or cravings for sensory experiences. The goal is for the patient to learn whether these controlling procedures truly work in the long run to regulate those internal experiences. The patient is asked to make a behavioral commitment to reducing hair pulling using Acceptance and Commitment Therapy, which involves reducing the habit while experiencing the urges to pull. The chapter compares urges to pull to a playground bully, who is better off ignored despite the difficulty of doing so.
Session 5: Acceptance of Pulling-Related Inner Experiences
Authors: Woods Douglas W. , Twohig Michael P. 
Published: January 2023

Abstract
This chapter explores the acceptance of pulling-related inner experiences. It explains that accepting the urges will result in the possible management of pulling and the chance to live life in accordance with one’s values. Learning to accept unpleasant private events allows people to experience feelings without letting them interfere with their life values. Acceptance is not about understanding hair pulling itself but rather about embracing unwanted inner experiences and taking an active stand against urges. Habit reversal training and trigger reduction strategies help the patient to control the actual activity of pulling hair and to stop engaging in behaviors that do not allow them to follow their values.
Session 8: Practicing Acceptance and Commitment Therapy (ACT)
Authors: Woods Douglas W. , Twohig Michael P. 
Published: January 2023

Abstract
This chapter introduces Acceptance and Commitment Therapy (ACT). It presents exercises that allow the patient to experience urges to pull without actually pulling hair. Learning to accept the presence of these urges is more useful than trying to control them. Practicing the skills of acceptance and defusion lets patients move away from their previous habits of controlling urges and other inner experiences and shift to a new approach that allows these feelings to be present. The chapter presents general guidelines and things to consider when practicing to function with urges. It highlights the importance of making room in the mind and allowing oneself to experience feelings when urge-provoking activities happen.
Session 3: Increasing Motivation for Treatment Through Values
Authors: Woods Douglas W. , Twohig Michael P. 
Published: January 2023

Abstract
This chapter details the third session of the Acceptance and Commitment Therapy (ACT) Enhanced Behavior Therapy for Trichotillomania (AEBT-T) treatment package. The therapist explains how clients often value things, such as being a good caregiver, spouse, or friend; being a great employee; being there for others; or being a good listener. However, the immediate rewards produced by pulling often outweigh the delayed rewards that come from behaving in a way that is more consistent with the aspects of life the client most values. The therapist helps the client see why time is spent talking about defining and following values, noting how this differs from following emotions. Thinking about values as things people do, rather than things people think and feel, can help the client conceptualize their own values.
Case 2
Authors: Frise Charlotte , Bhalsod Krupa , Scott Rebecca , Gibson Harry 
Published: January 2023

Abstract
A 26-year-old woman presented to the Emergency Department with a 10-day history of vomiting. Over the preceding 24 hours she had vomited approximately 10 times. She reported being unable to sustain any oral intake but had not had diarrhoea or abdominal pain. She had lost 5 kg of weight in the last few weeks (from a baseline of 52 kg). She had been diagnosed with asthma previously for which she used a regular steroid inhaler and salbutamol as required. She was on no other regular medications. A urinary pregnancy test was positive, and she thought her last menstrual period was 10 weeks previously.
Case 5
Authors: Frise Charlotte , Bhalsod Krupa , Scott Rebecca , Gibson Harry 
Published: January 2023

Abstract
A 36-year-old woman presented in spontaneous labour at 40 weeks of gestation. This was her first pregnancy and it had been uneventful to this point. She had no past medical history and was on no regular medications except multivitamins. She worked as a lawyer, did not smoke, drink alcohol, or take recreational drugs. She was a keen cyclist and had exercised throughout pregnancy. On presentation her blood pressure was 108/64 mmHg, and her urine showed 2+ ketones. During the following 12 hours she was given 2L of intravenous 5% glucose. She appeared to be a bit vague during labour, and was not always following the instructions of her midwife. Her husband was present and encouraged her throughout, including ensuring she drank 1L of water every 3 hours.