Risankizumab efficacy and safety based on prior inadequate response or intolerance to advanced therapy: post hoc analysis of the INSPIRE and COMMAND phase 3 studies.

Background And Aims: Treating ulcerative colitis (UC) in patients with prior advanced therapy (AT) exposure may be challenging. We report the efficacy and safety of risankizumab, a monoclonal interleukin 23p19 antibody, in patients with UC and prior inadequate response or intolerance to AT (AT-IR).

Methods: In the 12-week phase 3 INSPIRE induction study, patients were randomized to intravenous risankizumab 1200 mg or placebo.

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial.

Background: Whether it is effective and safe to extend the time window of intravenous thrombolysis up to 24 hours after the last known well is unknown. We aimed to determine the efficacy and safety of tenecteplase in Chinese patients with acute ischemic stroke due to large/medium vessel occlusion within an extended time window.

Methods: Patients with ischemic stroke presenting 4.

Sex Differences in Cardiovascular-Kidney-Metabolic Syndrome: 30-Year US Trends and Mortality Risks-Brief Report.

Background: The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remains unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and the long-term prognosis of CKM syndrome in the United States.

Linking Iris Cis-Regulatory Variants to Primary Angle-Closure Glaucoma Via Clinical Imaging and Multiomics.

Purpose: To elucidate the genetic basis of primary angle-closure glaucoma (PACG) by identifying pathogenic tissue and critical tissue-specific variants.

Methods: The correlations among PACG susceptibility, axial length (AL), and anterior chamber depth (ACD) were evaluated using meta-analyses. Propensity score matching was utilized on 2161 participants from the Handan Eye Study to determine the risk factors independent of ACD and AL for PACG.

A new species of Isonychia Eaton, 1871 (Ephemeroptera: Isonychiidae) from Taishun, China based on morphological characteristics and COX1 gene.

Isonychia taishunensis Huang, Shen, Zhang & Cheng sp. nov. is described based on larval samples from Taishun County, Zhejiang Province, China.

Chip-scale sensor for spectroscopic metrology.

Miniaturized spectrometers hold great promise for in situ, in vitro, and even in vivo sensing applications. However, their size reduction imposes vital performance constraints in meeting the rigorous demands of spectroscopy, including fine resolution, high accuracy, and ultra-wide observation window. The prevailing view in the community holds that miniaturized spectrometers are most suitable for coarse identification of signature peaks.

Cytological mapping of a powdery mildew resistance locus PmRc1 based on wheat-Roegneria ciliaris structural rearrangement library.

A powdery mildew (Pm) resistance locus PmRc1 was identified and transferred from Roegneria ciliaris into wheat. Two compensative translocation lines carrying PmRc1 were developed. Powdery mildew (Pm), caused by the biotrophic fungal pathogen Blumeria graminis f.

Associations of Metabolically Healthy Obesity and Retinal Age Gap.

Purpose: We investigated the association between metabolically healthy obesity (MHO) and retinal age gap and explored potential sex differences in this association.

Methods: This study included 30,335 participants from the UK Biobank. Body mass index (BMI) was classified into normal weight, overweight, and obesity.

Prediction for children with autism spectrum disorder based on digital behavioral features during free play.

Background: Play is an indispensable and meaningful activity in children's daily life. Research has shown that autistic children often exhibit differences in play development. The core traits of autism, such as distinct patterns in social interaction and communication, focused interests, and repetitive behaviors, frequently manifest in their play.

Development of an orally bioavailable CDK12/13 degrader and induction of synthetic lethality with AKT pathway inhibition.

Cyclin-dependent kinases 12/13 play pivotal roles in orchestrating transcription elongation, DNA damage response, and maintenance of genomic stability. Biallelic CDK12 loss has been documented in various malignancies. Here, we develop a selective CDK12/13 PROTAC degrader, YJ9069, which effectively inhibits proliferation in subsets of prostate cancer cells preferentially over benign immortalized cells.

Vaccine Potency and Structure of Yeast-Produced Polio Type 2 Stabilized Virus-like Particles.

Poliovirus (PV) is on the brink of eradication due to global vaccination programs utilizing live-attenuated oral and inactivated polio vaccines. Recombinant PV virus-like particles (VLPs) are emerging as a safe next-generation vaccine candidate for the impending polio-free era. In this study, we investigate the production, antigenicity, thermostability, immunogenicity, and structures of VLPs derived from PV serotype 2 (PV2) wildtype strain and thermally stabilized mutant (wtVLP and sVLP, respectively).

Omega-3 Polyunsaturated Fatty Acids as a Protective Factor for Myopia.

Purpose: Animal models suggest omega-3 polyunsaturated fatty acids (PUFAs) may protect against myopia by modulating choroidal blood perfusion, but clinical evidence is scarce and mixed. We aimed to determine the causality between omega-3 PUFAs and myopia using Mendelian randomization (MR) analysis.

Design: Two-sample MR analysis.

Bridging the Gap: Comparing Patient-Clinician Views on Treatment Goals and Communication in the Management of Atopic Dermatitis Within the Asia-Pacific Region.

Introduction: It remains unclear how patients with atopic dermatitis (AD) and clinicians perceive the level of patient-clinician communication and if there could be potential lapses. This cross-sectional study aims to compare perspectives between patients with AD and dermatologists regarding communication and treatment expectations in Asia.

Methods: Moderate-to-severe patients with AD and practicing dermatologists were recruited from eight Asia-Pacific territories, including Mainland China, Hong Kong, India, Japan, Singapore, South Korea, Taiwan, and Thailand.

Mid-Infrared Photoacoustic Stimulation of Neurons through Vibrational Excitation in Polydimethylsiloxane.

Photoacoustic (PA) emitters are emerging ultrasound sources offering high spatial resolution and ease of miniaturization. Thus far, PA emitters rely on electronic transitions of absorbers embedded in an expansion matrix such as polydimethylsiloxane (PDMS). Here, it is shown that mid-infrared vibrational excitation of C─H bonds in a transparent PDMS film can lead to efficient mid-infrared photoacoustic conversion (MIPA).

Do low skeletal muscle bulk and disturbed body fat mass impact tumor recurrence in stage I/II hepatocellular carcinoma undergoing surgery? An observational cohort study.

Introduction: The influence of deranged body composition on stage I/II hepatocellular carcinoma (HCC) after surgery remains undetermined. The current study aimed to investigate the impact of low skeletal muscle bulk and disturbed body fat mass on the recurrence outcome of stage I/II HCC patients undergoing liver resection. The associated metabolomic alterations were also assessed.

Photoacoustic: A Versatile Nongenetic Method for High-Precision Neuromodulation.

High-precision neuromodulation plays a pivotal role in elucidating fundamental principles of neuroscience and treating specific neurological disorders. Optical neuromodulation, enabled by spatial resolution defined by the diffraction limit at the submicrometer scale, is a general strategy to achieve such precision. Optogenetics offers single-neuron spatial resolution with cellular specificity, whereas the requirement of genetic transfection hinders its clinical application.

Intestinal dual-specificity phosphatase 6 regulates the cold-induced gut microbiota remodeling to promote white adipose browning.

Gut microbiota rearrangement induced by cold temperature is crucial for browning in murine white adipose tissue. This study provides evidence that DUSP6, a host factor, plays a critical role in regulating cold-induced gut microbiota rearrangement. When exposed to cold, the downregulation of intestinal DUSP6 increased the capacity of gut microbiota to produce ursodeoxycholic acid (UDCA).

Factors Contributing to Non-Concordance Between End-of-Life Care and Advance Care Planning.

Context: Despite making do-not-resuscitate or comfort care decisions during advance care planning, terminally ill patients sometimes receive life-sustaining treatments as they approach end of life.

Objectives: To examine factors contributing to nonconcordance between end-of-life care and advance care planning.

Methods: In this longitudinal retrospective cohort study, terminally ill patients with a life expectancy shorter than six months, who had previously expressed a preference for do-not-resuscitate or comfort care, were followed up after palliative shared care intervention.