Experimental and artificial intelligence optimization of paint wastewater (PWW) coagulation using novel Phaseolus vulgaris seed extract (PVSE).

This study investigated the application of artificial intelligence algorithms (AIA) in the coagulation treatment of paint wastewater anchored by novel Phaseolus vulgaris seed extract (PVSE). Untreated wastewater discharge harms the ecosystem, and therefore harmful industrial effluent, such as paint wastewater, must be brought to safe discharge levels before being released into the environment. In addition to AIA, comprehensive characterization tests, coagulation kinetics, and process optimization were also executed. Characterization results revealed that total solid in the PWW was above allowable standard, justifying the need for effective particle decontamination. The XRD and FTIR characterization indicated that PVSE structure is amorphous with abundant amine groups. Results of analysis of variance (ANOVA) obtained from process modeling indicated that the coagulation-flocculation process was a nonlinear quadratic system (F-value = 45.51) which was mostly influenced by PVSE coagulant dosage (F-value = 222.48; standardized effect = 14.85). Artificial intelligence indicated that neural network training effectively captured the nonlinear nature of the system in ANN (RMSE = 0.00040194; R = 0.98497), and ANFIS (RMSE = 0.003961) algorithms. Regression coefficient obtained from process modeling highlighted the suitability of RSM (0.9662), ANN (0.9739), and ANFIS (0.9718) in forecasting the coagulation-flocculation process, while comparative statistical appraisal authenticated the superiority of ANN model over RSM and ANFIS models. The coagulation kinetics experiment, which used a coagulation kinetic model, revealed a constant flocculation constant (Kf-value) for all jar test batches and a strong association between the Menkonu coagulation-flocculation constant (Km) and Kf values. Best removal efficiency of 97.01 % was obtained using ANN coupled genetic algorithm optimization (ANN-GA) at PVSE dosage of 4 g/L, coagulation time of 29 min and temperature of 25.1oC.

A Genomics-Driven Artificial Intelligence-Based Model Classifies Breast Invasive Lobular Carcinoma and Discovers CDH1 Inactivating Mechanisms.

Artificial intelligence (AI)-systems can improve cancer diagnosis, yet their development often relies on subjective histological features as ground truth for training. Here, we developed an AI-model applied to histological whole-slide images (WSIs) using CDH1 bi-allelic mutations, pathognomonic for invasive lobular carcinoma (ILC) in breast neoplasms, as ground truth. The model accurately predicted CDH1 bi-allelic mutations (accuracy=0.95) and diagnosed ILC (accuracy=0.96). A total of 74% of samples classified by the AI-model as having CDH1 bi-allelic mutations but lacking these alterations displayed alternative CDH1 inactivating mechanisms, including a deleterious CDH1 fusion gene and non-coding CDH1 genetic alterations. Analysis of internal and external validation cohorts demonstrated 0.95 and 0.89 accuracy for ILC diagnosis, respectively. The latent features of the AI-model correlated with human-explainable histopathologic features. Taken together, this study reports the construction of an AI-algorithm trained using a genetic rather than histologic ground truth that can robustly classify ILCs and uncover CDH1 inactivating mechanisms, providing the basis for orthogonal ground truth utilization for development of diagnostic AI-models applied to WSI.

Gonadal status modulates large elastic artery stiffness in healthy middle-aged and older men.

Hypogonadism is a risk factor for cardiovascular disease (CVD) in men related, in part, to increased oxidative stress. Elevated large artery stiffness and central pulsatile hemodynamics (e.g., pulse pressure and wave reflection magnitude) are independent risk factors for CVD. However, whether large artery stiffness and central pulsatile hemodynamics are (1) elevated in hypogonadal men independent of traditional CVD risk factors and (2) related to increased oxidative stress is unknown. Young men (N = 23; 30 ± 4 years) and middle-aged/older (MA/O) men with normal (> 400-1000 ng/dL; n = 57; 59 ± 7 years) or low testosterone (< 300 ng/dL; n = 21; 59 ± 7 years) underwent assessments of large artery stiffness (carotid ß-stiffness via ultrasonography) and central pulsatile hemodynamics (pulse wave analysis; SphygmoCor XCEL) following an infusion of saline or vitamin C to test the tonic suppression of vascular function by oxidative stress. Carotid stiffness differed by age (p < 0.001) and gonadal status within MA/O men (low testosterone vs. normal testosterone: 9.3 ± 0.7 vs. 8.0 ± 0.3U, p = 0.036). Central pulsatile hemodynamics did not differ by age or gonadal status (p > 0.119). Vitamin C did not alter carotid stiffness in any group (p > 0.171). There was a significant group × infusion interaction on aortic reflection magnitude (p = 0.015). Vitamin C treatment reduced aortic reflection magnitude in young and MA/O men with normal testosterone (both p < 0.001) but not MA/O men with low testosterone (p = 0.891). Collectively, hypogonadism may accelerate age-related large artery stiffening in MA/O men with low testosterone, independent of CVD risk factors; however, this is not related to increased reactive oxygen species sensitive to an acute vitamin C infusion.

Who participates in value-based care models? Physician characteristics and implications for value-based care.

Value-based care (VBC) payment models are becoming increasingly prevalent as alternatives to the traditional fee-for-service paradigm. This research quantifies the relationship between physician characteristics and participation in VBC payment models using the Association of American Medical Colleges' 2022 National Sample Survey of Physicians. We specified logistic regressions using physician-level variables to assess associations with current and new participation in Accountable Care Organizations, Primary Care First model, capitation, and bundled payments. Our results indicate that most respondents engaged in at least 1 VBC. Participation varied based on several characteristics, and physician specialty was highly predictive of overall participation. Compared with primary care physicians (PCPs), hospital-based physicians (odds ratio [OR] = 0.6, P < .001), medical specialists (OR = 0.5, P < .001), psychiatrists (OR = 0.4, P < .001), and surgeons (OR = 0.5, P < .001) were less likely to participate in VBC models. Medical specialists and surgeons were less likely to participate in commercial capitation than PCPs, while medical specialists and obstetricians/gynecologists were more likely to participate in certain bundles than PCPs. We suggest several policies to close the cross-specialty participation gap by including specialists and appealing to providers and patients.

Combination Atezolizumab, Cobimetinib, and Vemurafenib as a Treatment Option in BRAF V600 Mutation-Positive Melanoma: Patient Selection and Perspectives.

The treatment landscape for advanced and metastatic melanoma has drastically changed in recent years, with the advent of novel therapeutic options such as immune checkpoint inhibitors and targeted therapies offering remarkable efficacy and significantly improved patient outcomes compared to traditional approaches. Approximately 50% of melanomas harbor activating BRAF mutations, with over 90% resulting in BRAF V600E. Tumors treated with BRAF inhibitor monotherapy have a high rate of developing resistance within six months. Combination therapy with MEK inhibitors helped to mitigate this treatment resistance and led to improved outcomes. Due to the up-regulation of PD-1/PD-L1 receptors in tumors treated with BRAF/MEK inhibitor therapy, further studies included a third combination agent, anti-PD-1/PD-L1 inhibitors. This triple combination therapy may have superior efficacy and a manageable safety profile when compared with single or double agent therapy regimens.

Effective treatment of advanced and metastatic melanoma can be challenging. Newer treatment methods for patients with BRAF-mutated tumors include a combination of drugs with different complementary mechanisms. These drugs include BRAF-inhibitors, MEK-inhibitors, and PD-1/PD-L1 inhibitors. When these three medications are used in combination, patients may have better response rates and survival outcomes, when compared to using just one or two of these medications together. Toxicity rates are higher with a triple-medication regimen, so careful patient selection is important to consider.

The clinical potential of radiomics to predict hematoma expansion in spontaneous intracerebral hemorrhage: a narrative review.

Spontaneous intracerebral hemorrhage (sICH) is associated with significant morbidity and mortality, with subsequent hematoma expansion (HE) linked to worse neurologic outcomes. Accurate, real-time predictions of the risk of HE could enable tailoring management-including blood pressure control or surgery-based on individual patient risk. Although multiple radiographic markers of HE have been proposed based on standard imaging, their clinical utility remains limited by a reliance on subjective interpretation of often ambiguous findings and a poor overall predictive power. Radiomics refers to the quantitative analysis of medical images that can be combined with machine-learning algorithms to identify predictive features for a chosen clinical outcome with a granularity beyond human limitations. Emerging data have supported the potential utility of radiomics in the prediction of HE after sICH. In this review, we discuss the current clinical management of sICH, the impact of HE and standard imaging predictors, and finally, the current data and potential future role of radiomics in HE prediction and management of patients with sICH.

Planned Dental Extractions After Radiation Therapy.

Importance: Nonrestorable teeth are recommended to be extracted prior to radiation therapy (RT). Occasionally, preradiation extractions introduce unacceptable delays in treatment initiation. Planned dental extractions immediately postradiation presents an alternative strategy, though outcomes are uncertain. Objective: To evaluate the feasibility and safety of dental extractions immediately postradiation. Design, Setting, and Participants: A prospective cohort study including patients planned for curative-intent RT but unable or unwilling to proceed with 1 or more extractions recommended pretreatment was carried out. From January 2020 to September 2022, 58 patients were screened and 50 enrolled. The dental care was performed at a single academic department and the cancer care at regional centers. Analysis took place between September 22, 2023, and June 10, 2024. Exposure: On completion of RT, patients were recommended to complete extractions as soon as feasible, and ideally within 4 months. Main Outcomes and Measures: The primary end point was the actuarial cumulative incidence of exposed alveolar bone noted by any practitioner at any time after extraction, calculated using Gray method with death as a competing risk. As a pilot study, no formal power calculation was performed; resources allowed for 50 evaluable patients. Results: Among the 50 participants enrolled, RT was nonoperative for 32 patients (64%) and postoperative for 18 patients (36%). Intensity-modulated RT (IMRT) was delivered in all patients. Of the 50 patients, 20 (40%) declined dental extractions immediately postradiation and the remaining 30 (60%) underwent a median (range) of 8.5 (1-28) extractions at a median (range) of 64.5 (13-152) days after RT. The median (IQR) follow-up for survivors without exposed bone was 26 (17-35) months from the end of RT. The 2-year cumulative incidence of any exposed bone was 27% (95% CI, 14%-40%). The 2-year incidence of exposed bone for those who underwent dental extractions immediately postradiation was 40% (95% CI, 22%-58%) and 7% (95% CI, 0%-22%) for those who did not. Of the 13 who developed exposed bone: 4 resolved, 1 was lost to follow-up, and 8 were confirmed as osteoradionecrosis. Conclusions and Relevance: This cohort study found that postradiation dental extractions incur considerable risk, even if performed within a 4-month window.

Ex Vivo Lung Perfusion and Primary Graft Dysfunction Following Lung Transplantation: A Contemporary United Network for Organ Sharing Database Analysis.

Background: Primary graft dysfunction (PGD) has detrimental effects on recipients following lung transplantation. Here, we determined the contemporary trends of PGD in a national database, factors associated with the development of PGD grade 3 (PGD3) and ex vivo lung perfusion's (EVLP) effect on this harmful postoperative complication. Methods: The United Network for Organ Sharing database was queried from 2015 to 2023, and recipients were stratified into No-PGD, PGD1/2, or PGD3. The groups were analyzed with comparative statistics, and survival was determined with Kaplan-Meier methods. Multivariable Cox regression was used to determine factors associated with increased mortality. PGD3 recipients were then stratified based on EVLP use prior to transplantation, and a 3:1 propensity match was performed to determine outcomes following transplantation. Finally, logistic regression models based on select criteria were used to determine risk factors associated with the development of PGD3 and mortality within 1 year. Results: A total of 21.4% of patients were identified as having PGD3 following lung transplant. Those with PGD3 suffered significantly worse perioperative morbidity, mortality, and had worse long-term survival. PGD3 was also independently associated with increased mortality. Matched EVLP PGD3 recipients had significantly higher use of ECMO postoperatively; however, they did not suffer other significant morbidity or mortality as compared to PGD3 recipients without EVLP use. Importantly, EVLP use prior to transplantation was significantly associated with decreased likelihood of PGD3 development, while having no significant association with early mortality. Conclusions: EVLP is associated with decreased PGD3 development, and further optimization of this technology is necessary to expand the donor pool.

Valproic acid targets IDH1 mutants through alteration of lipid metabolism.

Histone deacetylases (HDACs) have a wide range of targets and can rewire both the chromatin and lipidome of cancer cells. In this study, we show that valproic acid (VPA), a brain penetrant anti-seizure medication and histone deacetylase inhibitor, inhibits the growth of IDH1 mutant tumors in vivo and in vitro, with at least some selectivity over IDH1 wild-type tumors. Surprisingly, genes upregulated by VPA showed no enhanced chromatin accessibility at the promoter, but there was a correlation between VPA-downregulated genes and diminished promoter chromatin accessibility. VPA inhibited the transcription of lipogenic genes and these lipogenic genes showed significant decreases in promoter chromatin accessibility only in the IDH1 MT glioma cell lines tested. VPA inhibited the mTOR pathway and a key lipogenic gene, fatty acid synthase (FASN). Both VPA and a selective FASN inhibitor TVB-2640 rewired the lipidome and promoted apoptosis in an IDH1 MT but not in an IDH1 WT glioma cell line. We further find that HDACs are involved in the regulation of lipogenic genes and HDAC6 is particularly important for the regulation of FASN in IDH1 MT glioma. Finally, we show that FASN knockdown alone and VPA in combination with FASN knockdown significantly improved the survival of mice in an IDH1 MT primary orthotopic xenograft model in vivo. We conclude that targeting fatty acid metabolism through HDAC inhibition and/or FASN inhibition may be a novel therapeutic opportunity in IDH1 mutant gliomas.

Racial and Ethnic Disparities in Peri-and Post-operative Cardiac Surgery.

Purpose of Review: Despite efforts to curtail its impact on medical care, race remains a powerful risk factor for morbidity and mortality following cardiac surgery. While patients from racial and ethnic minority groups are underrepresented in cardiac surgery, they experience a disproportionally elevated number of adverse outcomes following various cardiac surgical procedures. This review provides a summary of existing literature highlighting disparities in coronary artery bypass surgery, valvular surgery, cardiac transplantation, and mechanical circulatory support. Recent Findings: Unfortunately, specific causes of these disparities can be difficult to identify, even in large, multicenter studies, due to the complex relationship between race and post-operative outcomes. Current data suggest that these racial/ethnic disparities can be attributed to a combination of patient, socioeconomic, and hospital setting characteristics. Summary: Proposed solutions to combat the mechanisms underlying the observed disparate outcomes require deployment of a multidisciplinary team of cardiologists, anesthesiologists, cardiac surgeons, and experts in health care equity and medical ethics. Successful identification of at-risk populations and the implementation of preventive measures are necessary first steps towards dismantling racial/ethnic differences in cardiac surgery outcomes.

3D chromatin-based variant-to-gene maps across 57 human cell types reveal the cellular and genetic architecture of autoimmune disease susceptibility.

A portion of the genetic basis for many common autoimmune disorders has been uncovered by genome-wide association studies (GWAS), but GWAS do not reveal causal variants, effector genes, or the cell types impacted by disease-associated variation. We have generated 3D genomic datasets consisting of promoter-focused Capture-C, Hi-C, ATAC-seq, and RNA-seq and integrated these data with GWAS of 16 autoimmune traits to physically map disease-associated variants to the effector genes they likely regulate in 57 human cell types. These 3D maps of gene cis -regulatory architecture are highly powered to identify the cell types most likely impacted by disease-associated genetic variation compared to 1D genomic features, and tend to implicate different effector genes than eQTL approaches in the same cell types. Most of the variants implicated by these cis -regulatory architectures are highly trait-specific, but nearly half of the target genes connected to these variants are shared across multiple autoimmune disorders in multiple cell types, suggesting a high level of genetic diversity and complexity among autoimmune diseases that nonetheless converge at the level of target gene and cell type. Substantial effector gene sharing led to the common enrichment of similar biological networks across disease and cell types. However, trait-specific pathways representing potential areas for disease-specific intervention were identified. To test this, we pharmacologically validated squalene synthase, a cholesterol biosynthetic enzyme encoded by the FDFT1 gene implicated by our approach in MS and SLE, as a novel immunomodulatory drug target controlling inflammatory cytokine production by human T cells. These data represent a comprehensive resource for basic discovery of gene cis -regulatory mechanisms, and the analyses reported reveal mechanisms by which autoimmune-associated variants act to regulate gene expression, function, and pathology across multiple, distinct tissues and cell types.

The Associations of Sensory Impairment With 10-Year Risk of Dementia and Alzheimer's Disease: The Health and Retirement Study, 2010-2020.

BACKGROUND: Studies have examined the association between dual sensory impairment and late-life cognitive outcomes in the U.S with inconsistent findings. OBJECTIVE: To examine the associations between sensory impairment and 10-year risk of dementia or Alzheimer's disease among U.S. adults aged ≥ 50. METHODS: A prospective cohort study based on the Health and Retirement Study from 2010 to 2020. Individuals aged ≥ 50 years without self-reported dementia and Alzheimer's disease in 2010 were included in the analysis. Self-reported visual and hearing impairments were measures in 2010. Main failure events included self-reported incident dementia and Alzheimer's disease over a 10-year follow-up period. Participants were categorized as having no visual or hearing impairment, visual impairment only, hearing impairment only, and dual sensory impairment. Fine-Gray competing risk regression model was applied to estimate the associations of sensory impairment with incident dementia and Alzheimer's disease, adjusted for demographic characteristics, health behaviors, and health conditions at baseline. RESULTS: Of 20,248 identified individuals, 14.6% had visual impairment only, 11.2% had hearing impairment only, and 9.1% had dual impairment at baseline. After adjusting for all covariates, dual sensory impairment was associated with higher risk of dementia (HR = 1.46, 95% CI: 1.23-1.73) and Alzheimer's disease (HR = 1.35, 95% CI: 1.03-1.76). Visual impairment only was also associated with incident dementia and Alzheimer's disease among individuals <65 years. CONCLUSION: Older adults in the U.S. with visual and hearing impairments simultaneously had a particularly greater risk of dementia and Alzheimer's disease, indicating the needs of targeted screening for timely treatment and further prevention of dementia and Alzheimer's disease.

Surgical Management of Ipsilateral Internal Carotid Artery Stenosis and Unruptured Intracranial Aneurysm: Case Review and Treatment Considerations.

Introduction The coexistence of carotid artery stenosis and a concomitant downstream ipsilateral unruptured intracranial aneurysm requires unique treatment considerations to balance the risk of thromboembolic complications from carotid artery stenosis and the risk of subarachnoid hemorrhage from intracranial aneurysm rupture. These considerations include the selection of optimal treatment modalities, the order and timing of interventions, and potential management of antiplatelet agents with endovascular approaches. We present strategies to optimize treatment in such a case. Case Report We discuss the case of a 69-year-old woman with 90% stenosis of the right internal carotid artery and an ipsilateral, wide-necked, 4.8-mm, irregular-appearing right A1-2 junction aneurysm with an associated daughter sac. Open, endovascular, and mixed treatment strategies were considered. The patient selected and underwent a staged, open treatment approach with a carotid endarterectomy followed by a right craniotomy for microsurgical clipping of the aneurysm 5 days later. Both procedures were performed on daily full-dose aspirin without complications. On follow-up, the right carotid artery was widely patent, the aneurysm was secured, and the patient remained at her neurologic baseline. Discussion The presented strategy for ipsilateral carotid artery stenosis and an unruptured intracranial aneurysm initially optimized cerebral perfusion to mitigate ischemic risks while permitting timely aneurysm intervention without a need for dual antiplatelet therapy or to traverse an earlier procedure site.

Gut phageome in Mexican Americans: a population at high risk for metabolic dysfunction-associated steatotic liver disease and diabetes.

Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of Inoviridae was associated with both diabetes and liver steatosis. Diabetes was further associated with the enrichment of predominantly temperate Escherichia phages, some of which possessed virulence factors. Liver steatosis was associated with the depletion of Lactococcus phages r1t and BK5-T, and enrichment of the globally prevalent Crassvirales phages, including members of genus cluster IX (Burzaovirus coli, Burzaovirus faecalis) and VI (Kahnovirus oralis). The Lactococcus phages showed strong correlations and co-occurrence with Lactococcus lactis, while the Crassvirales phages, B. coli, B. faecalis, and UAG-readthrough crAss clade correlated and co-occurred with Prevotella copri. In conclusion, we identified the gut phageome signatures for two closely linked metabolic diseases with significant global burden. These phage signatures may have utility in risk modeling and disease prevention in this high-risk population, and identification of potential bacterial targets for phage therapy.IMPORTANCEPhages influence human health and disease by shaping the gut bacterial community. Using stool samples from a high-risk Mexican American population, we provide insights into the gut phageome changes associated with diabetes and liver steatosis, two closely linked metabolic diseases with significant global burden. Common to both diseases was an enrichment of Inoviridae, a group of phages that infect bacterial hosts chronically without lysis, allowing them to significantly influence bacterial growth, virulence, motility, biofilm formation, and horizontal gene transfer. Diabetes was additionally associated with the enrichment of Escherichia coli-infecting phages, some of which contained virulence factors. Liver steatosis was additionally associated with the depletion of Lactococcus lactis-infecting phages, and enrichment of Crassvirales phages, a group of virulent phages with high global prevalence and persistence across generations. These phageome signatures may have utility in risk modeling, as well as identify potential bacterial targets for phage therapy.

Instrument-Assisted Soft Tissue Mobilization 2-Handed Grip Force Production Consistency During Simulated Treatment: A Technical Report.

CONTEXT: Instrument-assisted soft tissue mobilization (IASTM) continues to increase in popularity and utilization among manual therapists. Despite its popularity, little is known about the consistency in peak or average forces that clinicians apply when performing IASTM treatments with a 2-handed grip. The purpose of this study was to examine intraclinician consistency in peak and average forces when applying a 2-handed IASTM grip. DESIGN: Randomized crossover study conducted in a university biomechanics laboratory. METHODS: Five (5) licensed athletic trainers with prior IASTM training used 5 different IASTM instruments to apply simulated treatment. Average peak forces (Fpeak) and average mean forces (Fmean) were collected via force plate for all 5 IASTM instruments with a skin simulant attached. Descriptive statistics, coefficients of variation (CVs), box and density plots, and Bland-Altman plots were assessed. RESULTS: The clinicians' average Fpeak ranged from 3.0 N to 11.6 N and average Fmean from 1.9 N to 8.1 N. Fpeak CVs for all instruments ranged from 14% to 31%, and Fmean CVs ranged from 15% to 35%. Bland-Altman plots indicated that for both Fpeak and Fmean, 97% of the data points fell within the limits of agreement across instruments and clinicians. Mean differences across instruments ranged from 0.9 N (91.8 g) to 4.1 N (418.1 g) for Fpeak and from 1.0 N (102.0 g) to 2.8 N (285.5 g) for Fmean. Thus, CVs, box and density plots, and Bland-Altman plots supported general force application consistency. CONCLUSION: Trained IASTM clinicians produced consistent treatment application forces (ie, Fpeak and Fmean) within treatment sessions during 2-handed simulated application.

Shared sanitation facilities and risk of respiratory virus transmission in resource-poor settings: A COVID-19 modeling case study.

Water supply and sanitation are essential household services frequently shared in resource-poor settings. Shared sanitation can increase the risk of enteric pathogen transmission due to suboptimal cleanliness of facilities used by large numbers of individuals. It also can potentially increase the risk of respiratory disease transmission. As sanitation is an essential need, shared sanitation facilities may act as important respiratory pathogen transmission venues even with strict control measures such as stay-at-home recommendations in place. This analysis explores how behavioral and infrastructural conditions surrounding shared sanitation may individually and interactively influence respiratory pathogen transmission. We developed an individual-based community transmission model using COVID-19 as a motivating example parameterized from empirical literature to explore how transmission in shared latrines interacts with transmission at the community level. We explored mitigation strategies, including infrastructural and behavioral interventions. Our review of empirical literature confirms that shared sanitation venues in resource-poor settings are relatively small with poor ventilation and high use patterns. In these contexts, shared sanitation facilities may act as strong drivers of respiratory disease transmission, especially in areas reliant on shared facilities. Decreasing dependence on shared latrines was most effective at attenuating sanitation-associated transmission. Improvements to latrine ventilation and handwashing behavior were also able to decrease transmission. The type and order of interventions are important in successfully attenuating disease risk, with infrastructural and engineering controls being most effective when administered first, followed by behavioral controls after successful attenuation of sufficient alternate transmission routes. Beyond COVID-19, our modeling framework can be extended to address water, sanitation, and hygiene measures targeted at a range of environmentally mediated infectious diseases.

Patient Opportunities to Self-Schedule in a Large Multisite, Multispecialty Medical Practice: Program Description and Uptake of 7 Unique Processes for Patients to Successfully Self-Schedule (and Reschedule) Their Medical Appointments.

Introduction: Patient self-scheduling of medical appointments is becoming more common in many medical institutions. However, the complexity of scheduling multiple specialties, following scheduling guidelines, and managing appointment access requires a variety of processes for a diverse inventory of self-schedulable appointment types. Methods: From 7 unique patient self-scheduling methods, we captured counts of successfully self-scheduled and completed appointments. A process map was created to show the paths of 5 different primary self-scheduling processes (new appointment self-scheduling) and 2 secondary self-scheduling processes (existing appointment self-rescheduling). Results: There were 7 unique processes that led to 733,651 successfully self-scheduled completed visits from January 1 to December 31, 2023 at a multisite, multispecialty clinic. The self-scheduling processes consisted of the following: (1) Ticket offer (appointment "ticket" offers for specific visits generated by a provider order or system rules), the software "ticket" sent to the patient permits "admission" to self-schedule calendar templates (341,591 uses, 46.6%); (2) direct self-scheduled visit for prequalified visit types (203,593 uses, 27.6%); (3) self-reschedule option (patient option to reschedule existing appointment, 79,706 uses, 10.9%); (4) new patient self-scheduled visit via clinic website (does not require portal access, 54,367 uses, 7.4%). (5) automated waitlist self-rescheduled visit (38,649 uses, 5.3%); (6) automated waitlist self-scheduled visit of previously unscheduled visit (10,939 uses, 1.5%); and (7) self-triage self-scheduled visit (4806 uses, 0.7%). Conclusion: The processes for self-scheduling are expanding. Our multispecialty clinic has implemented 7 different processes to help patients successfully self-schedule medical appointments. Some of the processes occur before initial scheduling (such as self-triage), and some are implemented after successful scheduling has already occurred (self-rescheduling option and self-rescheduling aided by an automated waitlist). Continued research is needed to look for measures of success beyond the ability to complete a self-scheduled visit, including the accuracy of the booking (right provider, location, and length of visit).

Recognition and control of neutrophil extracellular trap formation by MICL.

Regulation of neutrophil activation is critical for disease control. Neutrophil extracellular traps (NETs), which are web-like structures composed of DNA and neutrophil-derived proteins, are formed following pro-inflammatory signals; however, if this process is uncontrolled, NETs contribute to disease pathogenesis, exacerbating inflammation and host tissue damage1,2. Here we show that myeloid inhibitory C-type lectin-like (MICL), an inhibitory C-type lectin receptor, directly recognizes DNA in NETs; this interaction is vital to regulate neutrophil activation. Loss or inhibition of MICL functionality leads to uncontrolled NET formation through the ROS-PAD4 pathway and the development of an auto-inflammatory feedback loop. We show that in the context of rheumatoid arthritis, such dysregulation leads to exacerbated pathology in both mouse models and in human patients, where autoantibodies to MICL inhibit key functions of this receptor. Of note, we also detect similarly inhibitory anti-MICL autoantibodies in patients with other diseases linked to aberrant NET formation, including lupus and severe COVID-19. By contrast, dysregulation of NET release is protective during systemic infection with the fungal pathogen Aspergillus fumigatus. Together, we show that the recognition of NETs by MICL represents a fundamental autoregulatory pathway that controls neutrophil activity and NET formation.