Citations

Objectives Uniformity artifacts caused by defective transducer elements or scanner malfunctions degrade diagnostic image quality. Traditional quality control (QC) methods, such as phantom testing and visual or quantitative image analysis, can be labor‐intensive and limited in test frequency. This study aims to develop a deep learning framework to detect uniformity artifacts and complement traditional QC. Methods Clinical median images were generated by aggregating co‐registered grayscale ultrasound images acquired by each transducer and computing median intensity values across the image stack. A pretrained ResNet‐18 model was fine‐tuned on a dataset consisting of clinical median images from linear and curvilinear transducers. The dataset was divided into training, validation, and testing subsets, ensuring no overlap between training and test transducers. To assess generalizability, the model was also evaluated on an independent test set of 396 phantom‐validated images from linear and curvilinear transducers. Results The model achieved 100% accuracy on the first dataset's test set. On the independent test set, it attained 87.4% accuracy with high sensitivity (0.84) and specificity (0.88), demonstrating robust generalization. Occlusion sensitivity maps confirmed the model's attention to uniformity artifact regions. Conclusion The deep learning framework using clinical median images demonstrated robust performance across several linear and curvilinear transducer models. It could be integrated into the clinical QC workflow by automating artifact detection in an effective and timely manner. In our practice, it can flag median images classified as artifact‐present, reducing human review time by approximately 80% while preserving detection accuracy.

Objective: Battlefield acupuncture (BFA) has gained widespread clinical use for patients presenting to emergency departments (EDs). This systematic review of randomized controlled trials (RCTs) aims to assess the efficacy and safety of BFA in ED settings. Methods: A literature search was conducted in OVID and Scopus databases for RCTs involving BFA applied in ED settings. The risk of bias was evaluated using the Cochrane Collaboration risk of bias tool, while the methodological quality of RCTs was assessed using the Jadad score. Due to the heterogeneity of the included studies, a qualitative analysis was performed. Results: Seven studies involving 758 patients met the eligibility criteria. Among these, five studies evaluated traditional BFA in conjunction with standard analgesia care, while two studies assessed modified BFA alongside standard care. Most of the included studies were found to have a high risk of bias, leading to an overall classification of low quality according to the Jadad criteria. A descriptive analysis was performed due to heterogeneity in the interventions, observational timepoints, and outcomes reported in the included studies. Positive results were demonstrated in 71% of the studies. The most common conditions documented as the primary ED presentation included back pain, acute abdominal pain, lower extremity pain, neck pain, and acute sore throat. Notably, no severe adverse events were reported. Conclusion: BFA may offer a safe adjunct to standard care for pain management in ED settings. However, the limited methodological rigor and small number of existing RCTs reduce confidence in the current evidence. Well-designed, robust studies are needed to clarify their effectiveness and support stronger clinical recommendations.

Context: Traditional Chinese medicine (TCM) techniques, grounded in TCM theory, offer flexible and personalized therapeutic strategies. Increasing evidence indicates that gut microbiota dysbiosis is closely associated with the onset and progression of various diseases, highlighting a complex mutual relationship. Investigating the interaction between TCM techniques and gut microbiota may provide both a theoretical and practical foundation for clinical application. However, comprehensive systematic analyses remain limited. Objective: This study aimed to identify core themes and emerging trends in research on the interactions between TCM techniques and gut microbiota. In addition, it sought to explore underlying correlations using data mining approaches to provide insights supporting clinical applications and mechanistic studies. Materials and Methods: A systematic literature review was conducted using the Web of Science Core Collection and China National Knowledge Infrastructure for bibliometric analysis. Co-occurrence analysis was performed using CiteSpace software to identify research characteristics and development trends. Key data were extracted and visualized through an interactive network diagram generated with Cytoscape. Results: Current research predominantly focuses on acupoint application, moxibustion, and TCM enema, all of which exhibit significant effects in promoting beneficial microbiota and suppressing pathogenic strains. The regulatory impact of these TCM techniques on gut microbiota is closely associated with inflammatory response pathways and immunity. Conclusions: TCM techniques are extensively applied in disease management. Among them, moxibustion, acupoint application, TCM enema, and Tuina remain prominent and evolving areas of interest. Further empirical research is warranted to elucidate the biological mechanism underpinning these effects within the guidance of TCM pattern theory.

Objectives: This study aims to identify retinal biomarkers of NOTCH3 mutation carriers using optical coherence tomography (OCT) data from the UK Biobank. Methods: We conducted a cross-sectional, matched case-control study of individuals with or without NOTCH3 mutation from the UK Biobank between 2006 and 2010. All participants had macular OCT scan and cognitive assessment. Cases were identified based on pathogenic/likely pathogenic NOTCH3 mutations and 1:1 matched with controls based on age, sex, hypertension, diabetes mellitus, and cigarette smoking status. Baseline characteristics and cognitive test scores were compared using χ 2 or Mann-Whitney U test appropriately. Macular thickness at central, inner, and outer subfields and at each retinal layer was compared using Wilcoxon signed-rank test. Results: Our analysis included 134 participants (67 cases, 67 controls) with a mean age of 54 ± 9 years. NOCTH3 mutation carriers performed worse in prospective memory ( P =0.043), verbal and numerical reasoning ( P =0.178), visual memory ( P =0.227), and processing speed ( P =0.101) than matched controls. There were no differences in visual acuity between the 2 groups. NOTCH3 mutation carriers had significantly thinner macular inner subfield at the superior ( P =0.006), temporal ( P =0.008), and nasal ( P =0.034) quadrants, and significantly thinner macular RNFL ( P =0.008) compared with age-, sex-, and vascular risk factor-matched controls. Conclusion: The presence of NOTCH3 mutation is associated with reduced thickness in the inner macular subfield and macular RFNL. These retinal changes may reflect early pericyte dysfunction and microvascular ischemia. Longitudinal studies are needed to assess the temporal relationship between these retinal changes, cerebrovascular disease progression, and clinical severity of disease.

GGGGCC (G 4 C 2 ) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Toxicity is thought to result from the accumulation of either repeat RNAs and/or dipeptide repeat proteins (DPRs) translated from repeat-containing transcripts through repeat-associated non-AUG (RAN) translation. To disentangle RNA from DPR toxicity, we mutated a CUG codon predominantly used to initiate DPR translation from all three reading frames. This mutation disrupted DPR synthesis while preserving the expression of repeat-containing RNAs. Despite the accumulation of RNA foci, behavioral deficits and pathological abnormalities, including p-TDP-43 inclusions, STING activation, motor neuron loss, neuroinflammation, and increased plasma neurofilament concentration, were alleviated in C9ORF72 mice. Base editing of the CUG codon also improved molecular phenotypes and survival in patient induced pluripotent stem cell–derived neurons, which highlights the potential of therapeutically targeting DPR production rather than repeat RNAs.

Abstract Multiple myeloma (MM) with t(11;14)(CCND1;IGH) remains the only subset sensitive to the BCL2 inhibitor venetoclax. However, not all patients with t(11;14)(CCND1;IGH) respond to treatment, and some progress early after initial response. To investigate this, we examined 44 whole-genome and whole-exome sequencing data samples from 34 patients with t(11;14) MM treated with venetoclax. The presence of mutations in the RAS pathway was strongly associated with shortened progression-free survival (PFS) and was validated in an independent cohort of 21 patients with MM. The presence of 1q gain was also associated with shorter PFS in patients without RAS mutations. In 10 patients with paired prevenetoclax and postvenetoclax treatment samples, postvenetoclax progression was recurrently driven by the selection of genomic events in the BCL2/MCL1 and RAS pathways and of high-risk features (eg, loss of TP53 and CDKN2C). Overall, our study shows that comprehensive genomic profiling can identify most mechanisms underlying resistance to BCL2 inhibition in t(11;14)(CCND1;IGH) MM.

ABSTRACT Background This post hoc analysis examined the reduction in monthly headache days ( MHDs ) by frequency category shifts and associated improvements following eptinezumab treatment. Methods The DELIVER trial evaluated eptinezumab in adults with migraine for whom 2–4 previous preventive treatments failed. During a 24‐week, double‐blind, placebo‐controlled period followed by a 48‐week extension period, participants received IV eptinezumab 100 mg, 300 mg, or placebo every 12 weeks, with all receiving eptinezumab beginning Week 25 (dose‐blinded). Participants were categorized by MHD frequency: > 14, 8–14, 4 to < 8, 1 to < 4, 0. MHD category shifts were evaluated in the total population and several subgroups (including participants with > 14 baseline MHDs and early ≥ 50% responders). In participants reporting < 8 MHDs after all doses, the associated changes in headache intensity and disease status were evaluated. Results Of randomized participants, 88% (782/890) completed the trial. The percentage of participants randomized initially to eptinezumab who reported < 4 MHDs was 23% (138/592) over Weeks 1–12 and 47% (236/498) over Weeks 61–72; 9% reported 0 MHDs after the final dose. Of participants randomized initially to eptinezumab who shifted from ≥ 8 MHDs at baseline to < 8 over Weeks 1–12, 71% (170/241) reported < 8 MHDs for the rest of the trial; of those who shifted from > 14 to < 8 MHDs, 66% (49/74) reported < 8 MHDs for the rest of the trial. Reduction to < 8 MHDs was associated with robust improvements in headache intensity and disease burden. Conclusions Eptinezumab was associated with sustained reduction in MHD category, with some achieving headache/migraine freedom in patients with a history of preventive treatments that failed. Trial Registration ClinicalTrials.gov (identifier: NCT04418765; https://www.clinicaltrials.gov/ct2/show/NCT04418765 ) and EudraCT (identifier: 2019‐004497‐25; https://www.clinicaltrialsregister.eu/ctr‐search/search?query=2019‐004497‐25 )

Hypoplastic left heart syndrome (HLHS) is the most lethal congenital heart disease (CHD) whose genetic basis remains elusive, likely due to oligogenic complexity. To identify regulators of cardiomyocyte (CM) proliferation relevant to HLHS, we performed a genome-wide siRNA screen in human iPSC-derived CMs, revealing ribosomal protein (RP) genes as the most prominent effectors of CM proliferation. Whole-genome sequencing of 25 HLHS proband–parent trios similarly showed enrichment of rare RP gene variants, including a damaging RPS15A promoter variant shared in a familial CHD case. Cross-species functional analyses demonstrated that perturbation of RP genes impairs cardiac growth: knockdown of RPS15A, RPS17, RPL26L1, RPL39, or RPS15 reduced CM proliferation, caused cardiac malformations in Drosophila , and produced hypoplastic or dysfunctional hearts in zebrafish. Genetic interactions between RP genes and key cardiac transcription factors (TBX5 and NKX2–7) further support their developmental role. Importantly, p53 suppression or Hippo activation partially rescued RP deficiency phenotypes. Together, these findings implicate RP genes as critical regulators of cardiogenesis and candidate contributors to HLHS.

Abstract This study delineates a novel multisystem caliber-persistent arteriopathy syndrome, fundamentally redefining the classical Dieulafoy's lesion from a localized gastrointestinal anomaly to a systemic congenital vasculopathy. Through integrated histopathological and genomic analysis of a forensic autopsy case, we identified pervasive arterial remodeling across seven organ systems— characterized by absent physiological tapering— indicating developmental angiogenic dysregulation. Whole-genome sequencing uncovered pathogenic variants in PDE8B , LRCH1 , and ADA genes, with functional enrichment analyses implicating dysregulated purine–cAMP signaling and cytoskeletal organization as core pathogenic mechanisms. These findings establish a genetic basis for the observed pan-vascular phenotype and highlight the necessity of systematic vascular screening in cases of unexplained multiorgan hemorrhage. This work provides a foundational framework for diagnosing and investigating congenital vascular malformations with hemorrhagic risk, urging a paradigm shift in clinical evaluation and etiological assessment.