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Background and Aims: Ustekinumab (UST) is an effective biologic for treatment of inflammatory bowel disease (IBD). However, some patients treated with UST have suboptimal clinical response with standard dosing. The aims of this study were to determine the effectiveness of UST dose intensification (DI), identify factors associated with DI, cumulative incidence of DI and persistence of UST among treated patients. Methods: Clinical data of patients with Crohn's disease (CD) and ulcerative colitis (UC) who received UST from September 2017 to October 2022 in Singapore General Hospital were collected. Primary outcome was defined as achieving corticosteroid‐free clinical remission, biochemical remission, endoscopic healing and/or transmural healing (CD). Statistical analysis was performed to identify factors, which are predictive of UST DI and effectiveness of UST DI. Results: Forty‐two patients (34 CD and 8 UC) underwent UST DI to either 6‐weekly (n = 19, 45.2%) or 4‐weekly (n = 23, 35.9%) and the median time to intensification was 31.1 weeks (17.8–65.7). Presence of perianal disease in CD (HR 4.9; 1.47–16.4) was associated with DI. After DI, 16 (38%) patients achieved primary outcome by week 52. The overall drug persistence rates at 1 year and 2 years were 75.7% (95% CI 62.9–84.6) and 63.5% (95% CI 49.9–74.3), respectively. Conclusion: Two third of IBD patients underwent DI while on UST treatment and the median time to DI was about 6 months after induction. CD patients with perianal disease is more likely to undergo DI. More than one third of dose‐intensified patients achieved remission by week 52. [ABSTRACT FROM AUTHOR]

PAX4 (Paired box 4), a transcription factor crucial in pancreatic beta cell development and function, is a rare cause of maturity-onset diabetes of the young (MODY). What is new? A novel PAX4 variant is verified by family segregation study to be likely pathogenic. A child below 10 years of age diagnosed to have PAX4-MODY, differing from previously reported paediatric cases diagnosed in adolescence. A child with diabetes diagnosed at age 8 years, harbored a PAX4 variant, c.890G>A (p.Gly297Asp), initially classified as variant of uncertain significance. Eleven family members (7 adults and 4 children) with and without diabetes across 3 generations were genotyped. The variant co-segregated with diabetes or prediabetes across 3 generations of the family. The variant is reclassified as likely pathogenic according to standard guidelines. Genetic testing is essential to confirm PAX4-MODY as the presentation is variable even within the same family. PAX4 mutation needs to be considered in MODY genetic testing in Asian patients. [ABSTRACT FROM AUTHOR]

Down syndrome (DS), characterised by compromised brain development and intellectual challenges, often manifests Alzheimer's disease (AD) -like symptoms. Utilising the Web of Science Core Collection (WOSCC) database from January 1, 2000, to July 31, 2023, we conducted a comprehensive bibliometric analysis using VOSviewer, CiteSpace, and the R package "bibliometrix." Analyses included co-authorship, co-citation, co-occurrence, cooperative network, reference, and keyword burst citation. Analysing 5,082 papers, the U.S. demonstrated prominence with the highest number of research organisations and citations. Keyword analysis revealed promising research areas, including "Alzheimer's disease," "development," "inflammation," and "neurogenesis". This 22-year survey of the brain with trisomy 21 research unveils key trends, contributors, and focal areas in DS neuropathogenesis. Notably, Alzheimer 's-related genes and proteins play a pervasive role in DS neuropathological processes across patients' lifespans. The study contributes foundational knowledge for advancing research and care in the DS neuropathogenesis domain., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

IGSF1 mutation is the commonest cause of mild to moderate isolated central congenital hypothyroidism and has an X-linked recessive inheritance, primarily affecting males. Other notable clinical features are macroorchidism with delayed pubertal testosterone rise, large birth weight, increased body mass index, low prolactin, transient growth hormone deficiency and low prolactin. Two male siblings with central hypothyroidism were found to have a novel IGSF1 c.3467T>A variant that was likely pathogenic based on the family segregation study. The proband, aged 3 years presented at 18 days old with prolonged jaundice while his 16-year-old brother was only detected to have central hypothyroidism after the proband's genetic analysis result was known. Both siblings were obese, had large birth weights, macroorchidism and low prolactin. The proband's brother had intellectual disability while the proband had normal development. This case study highlights the importance of evaluation for the IGSF1 variant in patients with unexplained central hypothyroidism, especially when accompanied by X-linked inheritance and macroorchidism. Family segregation analysis allows detection of other affected family members or carriers who may also benefit from thyroxine treatment.

Hepatic steatosis is becoming more common in Asia with prevalence becoming as common as Western countries. Concomitant Hepatitis B and hepatic steatosis is increasingly encountered in clinical practice. The interaction between the two concomitant conditions at both molecular level and clinical outcome remains to be explored. The present review is aimed at summarizing the existing literature on the complex interaction of the two-concomitant disease., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.