Mechanisms of uropathogenic E. coli mucosal association in the gastrointestinal tract

Urinary tract infections (UTIs) are highly recurrent and frequently caused by Uropathogeni

The foundational capabilities of large language models in predicting postoperative risks using clinical notes

Clinical notes recorded during a patient\u27s perioperative journey holds immense informational value. Advances in large language models (LLMs) offer opportunities for bridging this gap. Using 84,875 preoperative notes and its associated surgical cases from 2018 to 2021, we examine the performance of LLMs in predicting six postoperative risks using various fine-tuning strategies. Pretrained LLMs outperformed traditional word embeddings by an absolute AUROC of 38.3% and AUPRC of 33.2%. Self-supervised fine-tuning further improved performance by 3.2% and 1.5%. Incorporating labels into training further increased AUROC by 1.8% and AUPRC by 2%. The highest performance was achieved with a unified foundation model, with improvements of 3.6% for AUROC and 2.6% for AUPRC compared to self-supervision, highlighting the foundational capabilities of LLMs in predicting postoperative risks, which could be potentially beneficial when deployed for perioperative care

Ibrutinib for therapy of steroid-refractory chronic graft-versus-host disease: A multicenter real-world analysis

To examine the activity of ibrutinib in steroid-refractory chronic graft-versus-host disease (SR-cGVHD) after the US Food and Drug Administration approval, we conducted a multicenter retrospective study. Data were standardly collected (N = 270 from 19 centers). Involved organs included skin (75%), eye (61%), mouth (54%), joint/fascia (47%), gastrointestinal (GI) (26%), lung (27%), liver (19%), genital (7%), and others (4.4%). The National Institutes of Health (NIH) severity was mild in 5.7%, moderate 42%, and severe 53%. Thirty-nine percent had overlap subtype. Karnofsky performance status (KPS) was ≥80% in 72%. The median prednisone was 0.21 mg/kg (0-2.27). Ibrutinib was started at a median of 18.2 months after cGVHD onset and in earlier lines of therapy (second line, 26%; third, 30%; fourth, 21%; fifth, 9.6%; sixth, 10%; seventh or higher, 1.2%). Among evaluable patients, the 6-month NIH overall response rate (ORR; complete response [CR]/partial response [PR]) was 45% (PR 42%; CR 3%). The median duration of response was 15 months (range, 1-46). Liver involvement had association with 6-month ORR (multivariate [MVA] odds ratio, 5.49; 95% confidence interval [CI], 2.3-14.2; P \u3c .001). The best overall response was 56%, with most (86%) achieving by 1 to 3 months. With a median follow-up for survivors of 30.5 months, failure-free survival (FFS) was 59% (53%-65%) at 6 months and 41% (36%-48%) at 12 months. On MVA, increased age (hazard ratio [HR], 1.01; 95% CI, 1.0-1.02; P = .033), higher baseline prednisone (HR, 1.92; 95% CI, 1.09-3.38; P = .032), and lung involvement (HR, 1.58; 95% CI, 1.1-2.28; P = .016) had worse FFS. Ibrutinib discontinuation was most commonly due to progressive cGVHD (44%) or toxicity (42%). These data support that ibrutinib has activity in SR-cGVHD, provide new insight into factors associated with response and FFS, and demonstrate the toxicity profile associated with discontinuation

Germline predisposition in multiple myeloma

We present a study of rare germline predisposition variants in 954 unrelated individuals with multiple myeloma (MM) and 82 MM families. Using a candidate gene approach, we identified such variants across all age groups in 9.1% of sporadic and 18% of familial cases. Implicated genes included genes suggested in other MM risk studies as potential risk genes

Social media as a platform for cancer care decision-making among women: Internet survey-based study on trust, engagement, and preferences

BACKGROUND: Decision aids improve patient and clinician decision-making but are underused and often restricted to clinical settings. OBJECTIVE: Given limited studies analyzing the feasibility of disseminating decision aids through social media, this study aimed to evaluate the acceptability, trust, and engagement of women with social media as a tool to deliver online decision aids for cancer treatment. METHODS: To prepare for potential dissemination of a breast cancer decision aid via social media, a cross-sectional survey in February 2023 was conducted via Prime Panels, an online market research platform, of women aged 35-75 years in the United States. Demographics, health, cancer information-seeking behaviors, social media use, trust in social media for health information, as well as the likelihood of viewing cancer-related health information and clicking on decision aids through social media, were assessed. Statistical analyses included descriptive statistics, correlations, and multivariable ordinal regression. RESULTS: Of 607 respondents, 397 (65.4%) had searched for cancer information, with 185 (46.6%) using the internet as their primary source. Facebook (Meta) was the most popular platform (511/607, 84.2%). Trust in social media for health information was higher among Black (14/72, 19.4%) and Asian respondents (7/27, 25.9%) than among White respondents (49/480, 10.2%; P=.003). Younger respondents aged 35-39 years (17/82, 20.7%) showed higher trust than those aged 70-79 years (12/70, 17.1%; P\u3c.001). Trust in social media for health information was linked to a higher likelihood of viewing cancer information and accessing a decision aid online (P\u3c.001). Participants who rated social media as Trustworthy (n=73) were more likely to view cancer information (61/73, 83.6%) and click on decision aids (61/73, 83.6%) than those who found it Untrustworthy (n=277; view: 133/277, 48.0%; click: 125/277, 45.1%). Engagement with social media positively correlated with viewing online cancer information (Spearman ρ=0.20, P\u3c.001) and willingness to use decision aids (ρ=0.21, P\u3c.001). Multivariable ordinal regression analyses confirmed that perception of social media\u27s trustworthiness is a significant predictor of engagement with decision aids (untrustworthy vs trustworthy β=-1.826, P\u3c.001; neutral vs trustworthy β=-0.926, P=.007) and of viewing cancer information (untrustworthy vs trustworthy β=-1.680, P\u3c.001, neutral vs trustworthy β=-0.581, P=.098), while age and employment status were not significant predictors. CONCLUSIONS: This exploratory study suggests that social media platforms may increase access to health information and decision aids. No significant differences were observed between demographic variables and the use or trust in social media for health information. However, trust in social media emerged as a mediating factor between demographics and engagement with cancer information online. Before disseminating decision aids on social media, groups should identify existing trust and engagement patterns with different platforms within their target demographic

Measuring and interpreting individual differences in fetal, infant, and toddler neurodevelopment

As scientists interested in fetal, infant, and toddler (FIT) neurodevelopment, our research questions often focus on how individual children differ in their neurodevelopment and the predictive value of those individual differences for long-term neural and behavioral outcomes. Measuring and interpreting individual differences in neurodevelopment can present challenges: Is there a standard way for the human brain to develop? How do the semantic, practical, or theoretical constraints that we place on studying development influence how we measure and interpret individual differences? While it is important to consider these questions across the lifespan, they are particularly relevant for conducting and interpreting research on individual differences in fetal, infant, and toddler neurodevelopment due to the rapid, profound, and heterogeneous changes happening during this period, which may be predictive of long-term outcomes. This article, therefore, has three goals: 1) to provide an overview about how individual differences in neurodevelopment are studied in the field of developmental cognitive neuroscience, 2) to identify challenges and considerations when studying individual differences in neurodevelopment, and 3) to discuss potential implications and solutions moving forward

Patients\u27 attitudes to magnetic resonance imaging in perianal fistulizing Crohn\u27s disease: A global survey

BACKGROUND: There is limited patient involvement in radiological research for perianal fistulizing Crohn\u27s disease (pfCD), despite magnetic resonance imaging (MRI)\u27s critical role in diagnosis and management. Patient and public involvement is essential for aligning research with patient priorities. This study aimed to gather patient perspectives on the use of MRI in pfCD. METHODS: A mixed-methods approach was used, following Guidance for Reporting Involvement of Patients and the Public (GRIPP2) guidelines. An online survey, co-developed with a patient representative, included open and closed questions on MRI experiences, advantages, challenges, and the potential for Artificial Intelligence (AI)-generated reports. This was followed by a virtual session for further exploration of patient views. Thematic analysis was conducted on the data. RESULTS: Forty-seven patients with Crohn\u27s disease (37 with pfCD) from 6 countries participated, with 28/37 (76%) completing the survey. Key themes included patient expectations for MRI, preferences for scan intervals, and report content. Most (93%) wanted MRI reports to compare with previous scans, highlighting fistula changes and new abscesses. A majority (57%) preferred MRI scans annually when well, and more frequently after surgery (64.3% preferred scans at 3 months). Emotional relief was associated with MRI improvements, though access to services and report clarity remained challenging. Interest in AI-generated reports was expressed if clearly explained and validated by professionals. CONCLUSIONS: This is the first study exploring patient views on MRI use in pfCD, emphasizing the need for patient-centred MRI reporting and clearer communication. Future work should enhance patient access and validate AI-generated MRI reports

Racial equity in urine drug screening policies in labor and delivery

IMPORTANCE: Black pregnant patients are significantly more likely than their White counterparts to undergo peripartum urine drug screening (UDS) and subsequent reporting to child protective services (CPS). OBJECTIVE: To evaluate the association of removing isolated cannabis use and limited prenatal care as order indications, combined with clinician-facing clinical decision support, with racial parity in peripartum UDS and CPS reporting. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study assessed 9396 pregnant patients at a single tertiary care center in a Midwestern US urban metropolitan region who delivered before (June 1, 2021, to September 31, 2022) and after (October 1, 2022, to January 31, 2024) the intervention. EXPOSURE: Updated UDS indications combined with clinical decision support. MAIN OUTCOMES AND MEASURES: Primary outcomes included UDS and CPS report rate by race before vs after the intervention. The secondary outcome was the rate of nonprescribed, noncannabis substance-positive UDS. Neonatal outcomes were included as balancing measures. RESULTS: Of 9396 female patients (median [IQR] age, 29 [24-33] years; 4305 [45.8%] Black, 4277 [45.5%] White, and 814 [8.7%] other race) included in the analysis, 4639 and 4757 delivered in the preintervention and postintervention periods, respectively. There was a small but statistically significant decrease in the number of Black patients before vs after the intervention (2210 [47.6%] vs 2095 [44.0%], P = .005); there were no significant differences in other race groups, median age, or multiparity. Before the intervention, 513 (23.2%) and 228 (11.1%) Black and White patients, respectively, had UDS (P \u3c .001) compared with 95 (4.5%) and 79 (3.6%) Black and White patients, respectively, after the intervention (P = .40). Before the intervention, an association between Black race and CPS report was observed (249 [11.3%] Black and 119 [5.8%] White patients, P \u3c .001); there was no association between race and CPS report after the intervention (87 [4.2%] Black and 78 [3.5%] White patients, P = .67). There was no association between the intervention and the percentage of UDS results that were positive for nonprescribed, noncannabis substances (107 [2.5%] preintervention vs 88 [2.0%] postintervention; P = .14). There was no significant association between the intervention and any measured neonatal outcomes. CONCLUSIONS AND RELEVANCE: In this quality improvement study, removal of isolated cannabis use and limited prenatal care as UDS indications, coupled with clinical decision support, was associated with improved racial equity in UDS testing and CPS reporting. The intervention was not associated with a significant change in UDS positivity for nonprescribed, noncannabis substances. These findings suggest that this intervention improved equity in UDS practices without decreasing identification of clinically relevant substance use

Virologic effects of broadly neutralizing antibodies VRC01LS and VRC07-523LS on chronic HIV-1 infection

BACKGROUNDHIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs) have emerged as promising interventions with the potential to effectively treat and prevent HIV-1 infections. We conducted a phase I clinical trial evaluating the potent CD4-binding site-specific (CD4bs-specific) bNAbs VRC01LS and VRC07-523LS in people with HIV-1 (PWH) not receiving antiretroviral therapy (ART).METHODSParticipants received a single intravenous 40 mg/kg dose of either VRC01LS (n = 7) or VRC07-523LS (n = 9) and did not initiate ART for a minimum of 14 days. The primary study objective was to evaluate safety and tolerability; the secondary study objectives were to evaluate pharmacokinetics (PK) and the impact of administered bNAbs on viral loads (VL) and CD4+ T cell counts in the absence of ART.RESULTSThis trial enrolled 16 PWH aged 20 to 57 years. Both bNAbs were safe and well tolerated. Mild local reactogenicity was only reported in participants who received VRC07-523LS, while both bNAbs were associated with mild systemic symptoms. Maximum serum concentrations (Cmax) following VRC01LS or VRC07-523LS were 1,566 ± 316 and 1,295 ± 376 μg/mL, respectively. VRC07-523LS administration significantly decreased VL in 8 out of 9 participants, with an average decline of 1.7 ± 0.8 log10 copies/mL within 14 days after administration. In contrast, VRC01LS administration resulted in a smaller average decline (0.8 ± 0.8 log10 copies/mL), and 3 out of 7 participants showedno change in VL. Postinfusion maximum decline in VL correlated with post hoc baseline in vitro viral susceptibility results for both bNAbs.CONCLUSIONThe results of this trial support inclusion of potent CD4bs-specific bNAbs, such as VRC07-523LS, into next-generation treatment regimens for HIV-1.TRIAL REGISTRATIONClinicalTrials.gov NCT02840474.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID)/NIH (grants UM1 AI068634, UM1 AI068636, UM1 AI106701, UM1AI069424, UM1AI069501, UM1AI69415, UM1AI069534, UM1AI69494); the Intramural Research Program of the NIAID/NIH; National Center for Advancing Translational Sciences/NIH (grants UM1TR004548, UL1TR001881, and UL1TR001878); and the National Cancer Institute/NIH (contract 75N91019D00024)