Jacobs Institute of Women's Health
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Participant engagement in a moderated Facebook group to promote COVID-19 vaccination
No full textInterventions with high levels of engagement have been found to be more effective at changing health behavior than those with low levels. Few prior studies have examined whether engagement in interventions using social media groups is associated with higher program effectiveness. This study examined whether participant engagement in a moderated private Facebook group aimed at COVID-19 vaccination was associated with improvements in immunization intentions (N = 263). Engagement in the group (i.e. emoji reactions, comments, poll votes and posts) and change in COVID-19 vaccine intentions were assessed through a retrospective review of participant engagement metrics and self-reported surveys at 4 weeks. Overall, 59% of participants engaged at least once. Participants on average made 11.9 total engagements during the 4-week study (SD = 25.5), of which 6.3 (SD = 15.2) were emoji reactions, 4.0 (SD = 12.3) comments, 1.4 (SD = 2.2) poll votes and 0.2 (SD = 0.7) post. No significant differences were found between engagement and sociodemographic characteristics or group size. Emoji reactions were associated with increased intentions. Each emoji reaction used was associated with a 4% increase in the odds of improvements in intention to vaccinate adjusted odds ratio (aOR) = 1.04, 95% CI: 1.01-1.08, P = 0.015). Future interventions on social media should encourage users to use emoji reactions on posts
Opposite regulation of intestinal and intrahepatic CD8 T cells controls alcohol-associated liver disease progression
No full textBACKGROUND: Gut-liver crosstalk plays an important role in alcohol-associated liver disease (ALD) pathogenesis; but underlying mechanisms remain obscure. OBJECTIVE: We examined the regulation of intestinal and intrahepatic CD8 T lymphocytes and their contribution to ALD. DESIGN: ALD patients were recruited for evaluation of intestinal and liver T cells. Single-cell RNA sequencing (scRNA seq) was performed to analyse intrahepatic and peripheral T cells in ALD. Wildtype, CD8-specific Bcl2 transgenic (Cd8 ), and Cd8 mice were subjected to chronic-plus-binge ethanol feeding. RESULTS: In ALD patients, duodenal CD8 T cells were selectively reduced and negatively correlated with liver injury and bacterial translocation markers, while intrahepatic CD8 T cells were markedly increased. ScRNA seq analysis of ALD patient livers revealed several populations of CD8 T cells expressing activation and survival genes (eg, Bcl2). Transcriptomics and functional studies revealed a key role of prosurvival BCL2 in this opposite regulation of CD8 T cells. Mechanistically, chronic-plus-binge ethanol feeding reduced CD8 T cells specifically in the duodenum where ethanol levels are high. Inducing BCL2 in CD8 T cells reversed ethanol-induced loss of duodenal CD8 T cells, improved gut barrier function and ameliorated ALD, while CD8 deficiency was linked to enhanced neutrophil and macrophage infiltration in the liver, exacerbating ALD in mice. CONCLUSIONS: ALD is associated with loss of duodenal CD8 T cells but elevation of intrahepatic CD8 T cells, which aggravates and ameliorates ALD, respectively. Restoration of survival and functions of intestinal and intrahepatic CD8 T cells may represent a novel therapeutic strategy for ALD patients
Polygenic Scores and Mood Disorder Onsets in the Context of Family History and Early Psychopathology
No full textIMPORTANCE: Bipolar disorder (BD) and major depressive disorder (MDD) aggregate within families, with risk often first manifesting as early psychopathology, including attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders. OBJECTIVE: To determine whether polygenic scores (PGS) are associated with mood disorder onset independent of familial high risk for BD (FHR-BD) and early psychopathology. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 7 prospective cohorts enriched in FHR-BD from Australia, Canada, the Netherlands, Spain, and the US. Participants with FHR-BD, defined as having at least 1 first-degree relative with BD, were compared with participants without FHR for any mood disorder. Participants were repeatedly assessed with variable follow-up intervals from July 1992 to July 2023. Data were analyzed from August 2023 to August 2024. EXPOSURES: PGS indexed genetic liability for MDD, BD, anxiety, neuroticism, subjective well-being, ADHD, self-regulation, and addiction risk factor. Semistructured diagnostic interviews with relatives established FHR-BD. ADHD or anxiety disorder diagnoses before mood disorder onset constituted early psychopathology. MAIN OUTCOMES AND MEASURES: The outcome of interest, mood disorder onset, was defined as a consensus-confirmed new diagnosis of MDD or BD. Cox regression examined associations of PGS, FHR-BD, ADHD, and anxiety with mood disorder onset. Kaplan-Meier curves and log-rank tests evaluated the probability of onset by PGS quartile and familial risk status. RESULTS: A total of 1064 participants (546 [51.3%] female; mean [SD] age at last assessment, 21.7 [5.1] years), including 660 with FHR-BD and 404 without FHR for any mood disorder, were repeatedly assessed for mental disorders. A total of 399 mood disorder onsets occurred over a variable mean (SD) follow-up interval of 6.3 (5.7) years. Multiple PGS were associated with onset after correcting for FHR-BD and early psychopathology, including PGS for ADHD (hazard ratio [HR], 1.19; 95% CI, 1.06-1.34), self-regulation (HR, 1.19; 95% CI, 1.06-1.34), neuroticism (HR, 1.18; 95% CI, 1.06-1.32), MDD (HR, 1.17; 95% CI, 1.04-1.31), addiction risk factor (HR, 1.16; 95% CI, 1.04-1.30), anxiety (HR, 1.15; 95% CI, 1.02-1.28), BD (HR, 1.14; 95% CI, 1.02-1.28), and subjective well-being (HR, 0.89; 95% CI, 0.79-0.99). High PGS for addiction risk factor, anxiety, BD, and MDD were associated with increased probability of onset in the control group. High PGS for ADHD and self-regulation increased rates of onset among participants with FHR-BD. PGS for self-regulation, ADHD, and addiction risk factors showed stronger associations with onsets of BD than MDD. CONCLUSIONS AND RELEVANCE: In this cohort study, multiple PGS were associated with mood disorder onset independent of family history of BD and premorbid diagnoses of ADHD or anxiety. The association between PGS and mood disorder risk varied depending on family history status
Kupffer cell and recruited macrophage heterogeneity orchestrate granuloma maturation and hepatic immunity in visceral leishmaniasis
No full textIn murine models of visceral leishmaniasis (VL), the parasitization of resident Kupffer cells (resKCs) drives early Leishmania infantum growth in the liver, leading to granuloma formation and subsequent parasite control. Using the chronic VL model, we demonstrate that polyclonal resKCs redistributed to form granulomas outside the sinusoids, creating an open sinusoidal niche that was gradually repopulated by monocyte-derived KCs (moKCs) acquiring a tissue specific, homeostatic profile. Early-stage granulomas predominantly consisted of CLEC4FKCs. In contrast, late-stage granulomas led to remodeling of the sinusoidal network and contained monocyte-derived macrophages (momacs) along with KCs that downregulated CLEC4F, with both populations expressing iNOS and pro-inflammatory chemokines. During late-stage infection, parasites were largely confined to CLEC4FKCs. Reduced monocyte recruitment and increased resKCs proliferation in infected Ccr2 mice impaired parasite control. These findings show that the ontogenic heterogeneity of granuloma macrophages is closely linked to granuloma maturation and the development of hepatic immunity in VL
Psychometric Validation of the Subject Sleep Diary in Patients with Moderate-to-Severe Atopic Dermatitis
No full textINTRODUCTION: A subject sleep diary (SSD) capturing 14 sleep parameters was developed to assess daily fluctuations in atopic dermatitis (AD)-associated sleep disturbance. This study aimed to evaluate the psychometric properties of the SSD using data including all randomized patients from the phase 3 ARCADIA 1 (NCT03985943) and ARCADIA 2 (NCT03989349) trials of nemolizumab in adults and adolescents (age ≥ 12 years) with moderate-to-severe AD. METHODS: Reliability, validity, and responsiveness of the SSD were evaluated, and its relationship with the single-item Sleep Disturbance Numerical Rating Scale (SD NRS) was examined using the equipercentile linking method. RESULTS: In ARCADIA 1 (N = 941), most SSD parameters showed good test-retest reliability (intraclass correlations ≥ 0.70) in patients with stable scores over 1 week on sleep disturbance or itch measures. The SSD parameters of wakefulness after sleep onset (WASO), total awake time (TWT), sleep efficiency (SE), number of times (NWASO-AD) and duration (WASO-AD) of AD-related WASO, and sleep quality/refresh (SQR) showed moderate or strong correlations (r = 0.30-0.66) at baseline, in the expected direction; with the SD NRS and at least one of the measures assessing itch and skin disease-related quality of life (Pruritus Categorical Scale, Peak Pruritus NRS, Average Pruritus NRS, and Dermatology Life Quality Index). Correlations with measures assessing distal concepts were weak for most sleep parameters. Sleep onset latency (SOL), WASO, TWT, SE, NWASO-AD, WASO-AD, and SQR demonstrated good known-groups validity at baseline and week 16, and showed responsiveness based on most anchors used in the analysis. Values of the same percentile rankings for the SD NRS and each SSD parameter were identified. Comparable results were obtained using ARCADIA 2 data (N = 787). CONCLUSIONS: The results provided evidence that the SSD, particularly its SOL, WASO, TWASO, TWT, SE, NWASO-AD, WASO-AD, and SQR parameters, is reliable and valid to measure multidimensional concepts of sleep disturbance in clinical studies. CLINICAL TRIAL REGISTRATION: NCT03985943, NCT03989349
Optimizing Large Language Models in Radiology and Mitigating Pitfalls: Prompt Engineering and Fine-tuning
No full textLarge language models (LLMs) such as generative pretrained transformers (GPTs) have had a major impact on society, and there is increasing interest in using these models for applications in medicine and radiology. This article presents techniques to optimize these models and describes their known challenges and limitations. Specifically, the authors explore how to best craft natural language prompts, a process known as prompt engineering, for these models to elicit more accurate and desirable responses. The authors also explain how fine-tuning is conducted, in which a more general model, such as GPT-4, is further trained on a more specific use case, such as summarizing clinical notes, to further improve reliability and relevance. Despite the enormous potential of these models, substantial challenges limit their widespread implementation. These tools differ substantially from traditional health technology in their complexity and their probabilistic and nondeterministic nature, and these differences lead to issues such as hallucinations, biases, lack of reliability, and security risks. Therefore, the authors provide radiologists with baseline knowledge of the technology underpinning these models and an understanding of how to use them, in addition to exploring best practices in prompt engineering and fine-tuning. Also discussed are current proof-of-concept use cases of LLMs in the radiology literature, such as in clinical decision support and report generation, and the limitations preventing their current adoption in medicine and radiology. RSNA, 2025 See invited commentary by Chung and Mongan in this issue
A meta-analysis of the utility of cryotherapy for preventing peripheral neuropathy among breast cancer patients receiving paclitaxel and nab-paclitaxel
No full textBACKGROUND: Cryotherapy with taxane infusion is a noninvasive strategy for preventing peripheral neuropathy (PN), but the efficacy of this approach has not been proven. METHODS: A systematic search was conducted, and 477 records were initially identified. The titles were screened independently by 2 reviewers. Fourteen studies were ultimately included for meta-analysis, which was conducted using the meta package in the R software. Only studies that analysed cryotherapy use in breast cancer patients who received paclitaxel or nab-paclitaxel were included. Relative risks (RRs) were calculated using the random effects model to compare the occurrence of PN between the paclitaxel and nab-paclitaxel groups. RESULTS: The incidence of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 PN was 24.85% (81/326) in the cryotherapy arm and 42.35% (72/170) in the placebo arm. The overall RR CTCAE grade ≥ 2 PN in the cryotherapy group compared with the placebo group was 0.45 [0.27, 0.77, p = 0.0031]. The RR for sensory PN was 0.19 [0.05, 0.66, p = 0.009], and that for motor PN was 0.18 [0.03, 0.99, p = 0.0491]. The RR for Patient Neurotoxicity Questionnaire (PNQ) scores ≥ D, which indicate severe neuropathy, was 0.24 [0.09, 0.62; p = 0.0035]. Cold intolerance was the most reported t adverse effect, with a prevalence of 15% (37/247). CONCLUSIONS: The use of cryotherapy decreased the occurrence of CTCAE grade ≥ 2 PN by 55%. Cold intolerance was the most frequently reported adverse effect associated with cryotherapy, but this adverse effect did not lead to high discontinuation rates
Fracture incidence in NCAA Women\u27s Sports during 2009/10-2018/19
No full textCONTEXT: While bone health remains a critical concern for women of all ages, there exists limited research on the comprehensive incidence of fractures among female collegiate athletes. OBJECTIVE: To describe the epidemiology of sport-related fractures across women\u27s National Collegiate Athletic Association (NCAA) sports. DESIGN: Descriptive epidemiology study. SETTING: Injury surveillance in collegiate women\u27s sports. PATIENTS OR OTHER PARTICIPANTS: Women competing in NCAA sports during 2009/10-2018/19. MAIN OUTCOME MEASURE(S): We examined fracture frequencies and distributions by sport, mechanism of injury, the injured body part, and injury history. We used a Bayesian framework to estimate fracture rates (per 10,000 AEs) by sport and event type. RESULTS: The NCAA ISP recorded 944 fractures across all women\u27s sports during the study period, and fractures were most frequently reported among lower extremity body parts. Fractures were most commonly reported as non-contact/overuse injuries (39.0%), although equipment/apparatus contact mechanisms accounted for \u3e 60% of fractures reported in field hockey and ice hockey. Fracture recurrence was most prevalently noted in track and field (17.8%) and gymnastics (17.6%). The posterior mean overall injury rate was 2.16 per 10,000 AEs (95% Credible Interval: [1.39, 3.44]), and the highest overall rate was estimated in gymnastics (Posterior mean= 6.29; 95% Credible Interval: [3.70, 10.31]). CONCLUSIONS: Our findings indicate that fractures in women\u27s gymnastics, lower leg fractures and fractures attributed to non-contact/overuse mechanisms, particularly among long-distance runners, warrant further attention in this population. Our results can inform targeted research efforts aimed at better understanding and improving bone health outcomes for female athletes
A combined endoscopic and ultrasonographic approach to a complex U4a uterine anomaly
No full textBACKGROUND: Uterine malformations are congenital anomalies arising from abnormal Müllerian duct development during embryogenesis. These can be linked to vaginal cysts, resulting in complex malformations. One rare form is the unicornuate uterus, where only one duct develops, leading to complications like severe pain due to a rudimentary, non-communicating horn. OBJECTIVES: To describe a combined approach using ultrasound, hysteroscopy, and robotic-assisted laparoscopy for complex uterine anomalies. PARTICIPANT: A 30-year-old nulliparous woman with unilateral kidney agenesis and acute pelvic pain referred to our centre. INTERVENTION: 2D ultrasound suggested a complex malformation. 3D ultrasound and magnetic resonance imaging confirmed a U4a uterus. Hysteroscopy revealed a hemicavity with one tubal ostium. Robotic-assisted laparoscopy enabled right salpingectomy and removal of the rudimentary horn while preserving the ovary. Intraoperative ultrasonography guided the drainage of vaginal cysts. As a result, vaginal cysts were drained, and the rudimentary horn was removed with ovarian preservation. The patient was discharged without complications and spontaneously conceived a healthy pregnancy 8 months later. CONCLUSIONS: Unicornuate uterus with non-communicating horn and renal agenesis is a rare condition. A combined approach using ultrasound, hysteroscopy, and robotic-assisted laparoscopy allows comprehensive evaluation and treatment. WHAT IS NEW?: This is the first reported case of simultaneous and synergistic use of hysteroscopy and robotic-assisted laparoscopy for complex genital malformations under ultrasonographic guidance