Prospective characterization of intestinal MRI intravoxel incoherent motion in pediatric and young adult patients with newly diagnosed small bowel Crohn's disease.

BACKGROUND: MRI diffusion-weighted imaging (DWI) is commonly used in MR enterography protocols for assessment of intestinal inflammation in patients with Crohn's disease. The intravoxel incoherent motion (IVIM) approach to DWI has been proposed as a more objective approach, providing quantitative parameters that reflect water diffusivity (D), blood flow (D*), and perfusion fraction (f). PURPOSE: We aimed to determine if DWI-IVIM metrics from the terminal ileum in patients with newly diagnosed Crohn's disease differ from healthy participants and change in response to biologic medical therapy. METHODS: In this prospective case-control study, 20 consecutive pediatric patients (mean age = 14 years ± 2 [SD]; eight females) with newly diagnosed ileal Crohn's disease and 15 pediatric healthy participants (mean age = 18 years ± 4 [SD]; eight females) underwent research MRI examinations of the small bowel between 12/2018 and 10/2021. Participants with Crohn's disease underwent MR studies at baseline, 6 weeks, and 6 months following initiation of anti-TNF-alpha therapy, whereas control participants underwent one research MRI examination. The MRI protocol included a DWI-IVIM sequence with nine b-values and the IVIM parameters (D, D*, and f) were extracted. Unpaired t-tests and mixed-effects models were used for analyses. RESULTS: Mean IVIM D (P < 0.001), D* (P = 0.004), and f (P = 0.001) metrics were lower for Crohn's patients at the time of diagnosis compared to healthy participants. Mean IVIM f value increased over time in response to medical therapy (mean f at baseline, 22% ± 6%; 6 weeks, 25% ± 7%; 6 months, 29% ± 10%; P = 0.016). Mean IVIM D* value increased over time in response to treatment (mean D* at baseline, 10.9 ± 3.0 × 10-3 mm2/s; 6 weeks, 11.8 ± 2.8 × 10-3 mm2/s; 6 months, 13.3 ± 3.3 × 10-3 mm2/s; P = 0.047), while there was no significant change in mean IVIM D value (P = 0.10). CONCLUSION: MRI DWI-IVIM metrics in patients with ileal Crohn's disease change over time in response to biological therapy and help discriminate these patients from healthy participants.

MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn's Disease.

BACKGROUND: Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. METHODS: This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. RESULTS: Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ±â€…13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon corrected Akaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). CONCLUSION: After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

Despite advances in medical therapy, many patients with ileal Crohn's disease progress to fibrostenosis requiring surgery. Our study has shown that GM-CSF autoantibodies and MRI biomarker sequences are associated with the need for ileal resection and may help guide management decisions.

Analgesia for the treatment of acute pancreatitis: a protocol for a systematic review and network meta-analysis.

INTRODUCTION: Gastrointestinal hospitalisations in the USA cause over US$130 billion in expenditures, and acute pancreatitis is a leading cause of these hospitalisations. Adequate pain control is one of the primary treatment goals for acute pancreatitis. Though opioids are commonly used for analgesia in these patients, there have been concerns about short-term and long-term side effects of using opioids. Recently, non-opioid medications have been studied to treat pain in patients with acute pancreatitis. This systematic review and network meta-analysis aims to assess the comparative efficacy of analgesic medication for non-severe, acute pancreatitis. METHODS AND ANALYSIS: We will search multiple electronic databases for randomised controlled trials that study pain management in patients with non-severe, acute pancreatitis. The intervention will be any analgesic for acute pancreatitis in the hospital setting. The comparison group will be patients who received a placebo or other active interventions for pain management. The primary outcomes of interest include pain scores and the need for supplementary analgesia. The secondary outcomes will be serious adverse events, local complications, progression to severe pancreatitis, transfer to the intensive care unit, length of hospitalisation, time to start enteral feeds, 30-day all-cause mortality and Quality of Life Scale scores. If sufficient homogeneity exists among included studies, the findings will be pooled using a traditional pairwise and network meta-analysis. The risk of bias in randomised control trials will be evaluated using the Cochrane Risk of Bias Tool 2.0. The Grading of Recommendations, Assessment, Development, and Evaluation approach will be used to report the certainty of evidence. ETHICS AND DISSEMINATION: This systematic review will not involve direct contact with human subjects. The findings of this review will be published in a peer-reviewed journal. They will give healthcare providers a better awareness of the optimal analgesic medication for pain treatment in non-severe, acute pancreatitis.

Preoperative Risk Factors for 1-year Mortality in Patients Undergoing Fenestrated Endovascular Aortic Aneurysm Repair in the US-Aortic Research Consortium.

BACKGROUND: Early survival (1-year) following elective repair of complex abdominal aortic aneurysms (AAA) or thoracoabdominal aortic aneurysms (TAAA) can be utilized as an indicator of successful repair and provides a reasonable countermeasure to the annual rupture risk based on diameter. We aimed to identify preoperative factors associated with 1-year mortality following F/BEVAR and develop a predictive model for 1-year mortality based on patient-specific risk-profiles. METHODS: The US-Aortic Research Consortium (US-ARC) database was queried for all patients undergoing elective F/BEVAR for complex AAA or TAAA from 2005-2022. The primary outcome was 1-year survival based on preoperative risk-profile. Multivariable Cox regression was used to determine preoperative variables associated with 1-year mortality overall and by extent of aortic pathology. Logistic regression was performed to build a predictive model for 1-year mortality based on number of risk factors present. RESULTS: A total of 2,099 patients met the inclusion criteria for this study (complex AAA: N=709, 34.3%; Type 1-3 TAAA: N=777, 37.6%; Type 4-5 TAAA: N=580, 28.1%). Multivariable Cox regression identified the following significant risk factors associated with 1-year mortality: current smoker, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), Aortic diameter>7cm, Age>75, Extent 1-3, creatinine>1.7mg/dL, and hematocrit<36%. When stratified by extent of aortic involvement, multivariable Cox regression revealed risk factors for 1-year mortality in complex AAA (CHF max aortic diameter>7cm, hematocrit<36mg/dL, and current smoking status), Type 1-3 TAAA (COPD, CHF, and Age>75) and Type 4-5 TAAA (age>75, creatinine>1.7mg/dL, and hematocrit<36mg/dL). Logistic regression was then utilized to develop a predictive model for 1-year mortality based on patient risk-profile. Appraisal of the model revealed an area under the curve of 0.64, p-value<0.001, and observed to expected ratio of 0.85. CONCLUSIONS: This study describes multiple risk factors associated with an increase in 1-year mortality following F/BEVAR. Given that elective repair of complex AAA or TAAA is offered to some patients in whom future rupture risk outweighs operative risk, these findings suggest that highly comorbid patients with smaller aneurysms may not benefit from repair. Descriptive and predictive models for 1-year mortality based on patient risk-profiles can serve as an adjunct in clinical decision-making when considering elective F/BEVAR.

Environmental Factors Associated with Risk of Crohn's Disease Development in the CCC-GEM Project.

BACKGROUND AND AIMS: To date, it is unclear how environmental factors influence Crohn's Disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers. METHODS: We studied 4,289 healthy first-degree relatives (FDRs) of CD patients from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project. Regression models identified environmental factors associated with future CD onset and their association with pre-disease biological factors, including altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio(LMR); gut inflammation via fecal calprotectin(FCP) levels; and fecal microbiome composition through 16S rRNA sequencing. RESULTS: Over a 5.62-year median follow-up, 86 FDRs developed CD. Living with a dog between ages 5-15 (HR=0.62; 95% CI=0.40-0.96; P = .034), and living with a large family size in the first year of life (HR=0.43; 95% CI=0.21-0.85; P = .016) were associated with decreased CD risk; whereas having a bird at the time of recruitment (HR=2.78; CI=1.36-5.68; P = .005) was associated with an increased CD risk. Furthermore, living with a dog was associated with reduced LMR, altered relative abundance of multiple bacterial genera, and increased Chao1 diversity; while bird owners had higher FCP levels. Large family during participants' first year of life was associated with altered microbiota composition without affecting FCP or LMR. CONCLUSION: This study identifies environmental variables associated with CD risk. These variables were also associated with altered barrier function, subclinical inflammation, and gut microbiome composition shifts, suggesting potential roles in CD pathogenesis.

Calculation of Overall Hospital Quality Star Ratings With and Without Inclusion of the Peer Grouping Step.

Importance: The Centers for Medicare & Medicaid Services (CMS) Overall Star Rating is widely used by patients and consumers, and there is continued stakeholder curiosity surrounding the inclusion of a peer grouping step, implemented to the 2021 Overall Star Rating methods. Objective: To calculate hospital star rating scores with and without the peer grouping step, with the former approach stratifying hospitals into 3-, 4-, and 5-measure group peer groups based on the number of measure groups with at least 3 reported measures. Design, Setting, and Participants: This cross-sectional study used Care Compare website data from January 2023 for 3076 hospitals that received a star rating in 2023. Data were analyzed from April 2023 to December 2023. Exposure: Peer grouping vs no peer grouping. Main Outcomes and Measures: The primary outcome was the distribution of star ratings, with 1 star being the lowest-performing hospitals and 5 stars, the highest. Analyses additionally identified the number of hospitals with a higher, lower, or identical star rating with the use of the peer grouping step compared with its nonuse, stratified by certain hospital characteristics. Results: Among 3076 hospitals that received a star rating in 2023, most were nonspecialty (1994 hospitals [64.8%]), nonteaching (1807 hospitals [58.7%]), non-safety net (2326 hospitals [75.6%]), non-critical access (2826 hospitals [91.9%]) hospitals with fewer than 200 beds (1822 hospitals [59.2%]) and located in an urban geographic designations (1935 hospitals [62.9%]). The presence of the peer grouping step resulted in 585 hospitals (19.0%) being assigned a different star rating than if the peer grouping step was absent, including considerably more hospitals receiving a higher star rating (517 hospitals) rather than a lower (68 hospitals) star rating. Hospital characteristics associated with a higher star rating included urbanicity (351 hospitals [67.9%]), non-safety net status (414 hospitals [80.1%]), and fewer than 200 beds (287 hospitals [55.6%]). Collectively, the presence of the peer grouping step supports a like-to-like comparison among hospitals and supports the ability of patients to assess overall hospital quality. Conclusions and Relevance: In this cross-sectional study, inclusion of the peer grouping in the CMS star rating method resulted in modest changes in hospital star ratings compared with application of the method without peer grouping. Given improvement in face validity and the close association between the current peer grouping approach and stakeholder needs for peer-comparison, the current CMS Overall Star Rating method allows for durable comparisons in hospital performance.

Discovery of CVN293, a Brain Permeable KCNK13 (THIK-1) Inhibitor Suitable for Clinical Assessment.

The potassium (K+) ion channel KCNK13 is specifically expressed in human microglia with elevated expression observed in post-mortem human brain tissue from patients with Alzheimer's disease. Modulation of KCNK13 activity by a small-molecule inhibitor is proposed as a potential treatment for neurodegenerative diseases. Herein, we describe the evolution of a series of KCNK13 inhibitors derived from a high-throughput screening campaign, resulting in CVN293, a potent, selective, and brain permeable clinical candidate molecule. CVN293 demonstrated a concentration-dependent inhibition of the NLRP3-inflammasome mediated production of IL-1ß from LPS-primed murine microglia. Cross-species pharmacokinetic data of CVN293 are also disclosed. These findings support the advancement of CVN293 in clinical trials.

Correction: Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies.

[This corrects the article DOI: 10.1371/journal.pone.0253364.].

Hong Kong consensus recommendations on the management of pancreatic ductal adenocarcinoma.

This project was undertaken to develop the first set of consensus statements regarding the management of pancreatic ductal adenocarcinoma (PDAC) in Hong Kong, with the goal of providing guidance to local clinicians. A multidisciplinary panel of experts discussed issues surrounding current PDAC management and reviewed evidence gathered in the local context to propose treatment recommendations. The experts used the Delphi approach to finalise management recommendations. Consensus was defined as ≥80% acceptance among all expert panel members. Thirty-nine consensus statements were established. These statements cover all aspects of PDAC management, including diagnosis, resectability criteria, treatment modalities according to resectability, personalised management based on molecular profiling, palliative care, and supportive care. This project fulfils the need for guidance regarding PDAC management in Hong Kong. To assist clinicians with treatment decisions based on varying levels of evidence and clinical experience, treatment options are listed in several consensus statements.

Defining the mechanism of galectin-3-mediated TGF-ß1 activation and its role in lung fibrosis.

Integrin-mediated activation of the profibrotic mediator transforming growth factor-ß1 (TGF-ß1), plays a critical role in idiopathic pulmonary fibrosis (IPF) pathogenesis. Galectin-3 is believed to contribute to the pathological wound healing seen in IPF, although its mechanism of action is not precisely defined. We hypothesized that galectin-3 potentiates TGF-ß1 activation and/or signaling in the lung to promote fibrogenesis. We show that galectin-3 induces TGF-ß1 activation in human lung fibroblasts (HLFs) and specifically that extracellular galectin-3 promotes oleoyl-L-α-lysophosphatidic acid sodium salt-induced integrin-mediated TGF-ß1 activation. Surface plasmon resonance analysis confirmed that galectin-3 binds to αv integrins, αvß1, αvß5, and αvß6, and to the TGFßRII subunit in a glycosylation-dependent manner. This binding is heterogeneous and not a 1:1 binding stoichiometry. Binding interactions were blocked by small molecule inhibitors of galectin-3, which target the carbohydrate recognition domain. Galectin-3 binding to ß1 integrin was validated in vitro by coimmunoprecipitation in HLFs. Proximity ligation assays indicated that galectin-3 and ß1 integrin colocalize closely (≤40 nm) on the cell surface and that colocalization is increased by TGF-ß1 treatment and blocked by galectin-3 inhibitors. In the absence of TGF-ß1 stimulation, colocalization was detectable only in HLFs from IPF patients, suggesting the proteins are inherently more closely associated in the disease state. Galectin-3 inhibitor treatment of precision cut lung slices from IPF patients' reduced Col1a1, TIMP1, and hyaluronan secretion to a similar degree as TGF-ß type I receptor inhibitor. These data suggest that galectin-3 promotes TGF-ß1 signaling and may induce fibrogenesis by interacting directly with components of the TGF-ß1 signaling cascade.

Surveillance system integration: reporting the results of a global multicountry survey.

OBJECTIVES: Currently, there is no comprehensive picture of the global surveillance landscape. This survey examines the current state of surveillance systems, levels of integration, barriers and opportunities for the integration of surveillance systems at the country level, and the role of national public health institutes (NPHIs). STUDY DESIGN: This was a cross-sectional survey of NPHIs. METHODS: A web-based survey questionnaire was disseminated to 110 NPHIs in 95 countries between July and August 2022. Data were descriptively analysed, stratified by World Health Organization region, World Bank Income Group, and self-reported Integrated Disease Surveillance (IDS) maturity status. RESULTS: Sixty-five NPHIs responded. Systems exist to monitor notifiable diseases and vaccination coverage, but less so for private, pharmaceutical, and food safety sectors. While Ministries of Health usually lead surveillance, in many countries, NPHIs are also involved. Most countries report having partially developed IDS. Surveillance data are frequently inaccessible to the lead public health agency and seldomly integrated into a national public health surveillance system. Common challenges to establishing IDS include information technology system issues, financial constraints, data sharing and ownership limitations, workforce capacity gaps, and data availability. CONCLUSIONS: Public health surveillance systems across the globe, although built on similar principles, are at different levels of maturity but face similar developmental challenges. Leadership, ownership and governance, supporting legal mandates and regulations, as well as adherence to mandates, and enforcement of regulations are critical components of effective surveillance. In many countries, NPHIs play a significant role in integrated disease surveillance.

De Novo Crohn's Disease Diagnosed in the Setting of Acute SARS-Cov-2 Infection Requiring Escalation of Infliximab Therapy Guided by Personalized Pharmacokinetics.

Here, we describe a 7-year-old girl who was diagnosed with an early-onset Crohn's disease in the setting of COVID-19 illness. Her disease process responded poorly to standard infliximab dosing, necessitating repeat hospitalizations and red blood cell transfusions. Remission was subsequently induced using a personalized infliximab pharmacokinetic profile based on therapeutic drug monitoring. While the initial data does not support a link, several case reports suggest an association between COVID-19 illness and de-novo development of IBD, especially in young female patients. We report, to our knowledge, the youngest patient who developed early-onset Crohn's disease in the setting of concomitant SARS-CoV-2 infection.

Imaging and clinical predictors of surgery in stricturing ileal Crohn's disease: a retrospective study from a large pediatric hospital.

PURPOSE: (1) To determine the frequency of surgical management in children with Crohn's Disease (CD) and a new radiologic ileal stricture, and (2) to identify imaging and clinical features that predict the need for surgery. METHODS: This retrospective study included pediatric patients (< 21 years old) with CD and a new ileal stricture diagnosed by MRE, CTE, or CT between July 2018 and June 2023. Three board-certified radiologists recorded stricture length, maximum mural thickness, minimum lumen diameter, maximum upstream diameter, and simplified magnetic resonance index of activity (sMaRIA) score. Anthropometrics, laboratory data, and surgical interventions performed after stricture diagnosis were also recorded. Multivariable logistic regression was used to identify imaging and clinical variables associated with the need for surgery. RESULTS: 44 pediatric CD patients (median age 16.5 years) presented with a new ileal stricture during the study period. 30 (68.2%) patients required surgery, with a median time of 87.5 days between stricture diagnosis and surgery. Median stricture measurements were length: 7.0 cm, maximum mural thickness: 7.3 mm, minimum lumen diameter: 0.2 cm, and maximum upstream diameter: 3.3 cm. Median sMaRIA score was 3.0, and 14 (31.8%) strictures had associated internal penetrating disease. Stricture ratio (ratio of maximum upstream lumen diameter to minimum lumen diameter) (OR = 1.15 [95% CI 1.02-1.30]; p = 0.02) and sMaRIA (OR = 2.12 [95% CI 0.87-5.17; p = 0.10) were associated with need for surgery. CONCLUSION: Surgery remains common in stricturing pediatric CD, with increasing stricture ratio and sMaRIA score associated with need for surgical management.

Intra- and interspecific diversity in a tropical plant clade alter herbivory and ecosystem resilience.

Declines in biodiversity generated by anthropogenic stressors at both species and population levels can alter emergent processes instrumental to ecosystem function and resilience. As such, understanding the role of biodiversity in ecosystem function and its response to climate perturbation is increasingly important, especially in tropical systems where responses to changes in biodiversity are less predictable and more challenging to assess experimentally. Using large-scale transplant experiments conducted at five neotropical sites, we documented the impacts of changes in intraspecific and interspecific plant richness in the genus Piper on insect herbivory, insect richness, and ecosystem resilience to perturbations in water availability. We found that reductions of both intraspecific and interspecific Piper diversity had measurable and site-specific effects on herbivory, herbivorous insect richness, and plant mortality. The responses of these ecosystem-relevant processes to reduced intraspecific Piper richness were often similar in magnitude to the effects of reduced interspecific richness. Increased water availability reduced herbivory by 4.2% overall, and the response of herbivorous insect richness and herbivory to water availability were altered by both intra- and interspecific richness in a site-dependent manner. Our results underscore the role of intraspecific and interspecific richness as foundations of ecosystem function and the importance of community and location-specific contingencies in controlling function in complex tropical systems.

Nutritional Characterization of Chilean Landraces of Common Bean.

Common bean (Phaseolus vulgaris L.) is the primary grain legume cultivated worldwide for direct human consumption due to the high nutritional value of its seeds and pods. The high protein content of common beans highlights it as the most promising source of plant-based protein for the food industry. Additionally, landraces of common bean have great variability in nutritional traits, which is necessary to increase the nutritional quality of elite varieties. Therefore, the main objective of this study was to nutritionally characterize 23 Chilean landraces and 5 commercial varieties of common bean to identify genotypes with high nutritional value that are promising for the food industry and for genetic improvement programs. The landrace Phv23 ('Palo') was the most outstanding with high concentrations of minerals such as P (7.53 g/kg), K (19.8 g/kg), Mg (2.43 g/kg), Zn (52.67 mg/kg), and Cu (13.67 mg/kg); essential amino acids (364.8 mg/g protein); and total proteins (30.35 g/100 g seed). Additionally, the landraces Phv9 ('Cimarrón'), Phv17 ('Juanita'), Phv3 ('Araucano'), Phv8 ('Cabrita/Señorita'), and Phv4 ('Arroz') had a high protein content. The landrace Phv24 ('Peumo') stood out for its phenolic compounds (TPC = 218.1 mg GA/100 g seed) and antioxidant activity (ORAC = 22,167.9 µmol eq trolox/100 g extract), but it has moderate to low mineral and protein concentrations. In general, the concentration of nutritional compounds in some Chilean landraces was significantly different from the commercial varieties, highlighting their high nutritional value and their potential use for the food industry and for genetic improvement purposes.

Loranthus tanakae Franch. and Sav. Attenuates Respiratory Inflammation Caused by Asian Sand Dust.

Asian sand dust (ASD), generally produced in East Asia, including China, Japan, and Korea, directly leads to the development of pulmonary disease and exacerbates underlying pulmonary diseases. Loranthus tanakae Franch. and Sav. is a traditional herbal medicine applied to improve various inflammatory conditions. Here, we evaluated the curative properties of L. tanakae ethanol extract (LTE) against pulmonary inflammation caused by ASD. Additionally, to investigate the mechanism of action of LTE, we performed network pharmacological analysis. ASD was administrated on day 1, 3, and 5 by intranasal instillation, and LTE was orally administered for 6 days. Administration of LTE significantly decreased inflammatory cytokines and the number of inflammatory cells in bronchoalveolar lavage fluid, which was accompanied by a decrease in inflammatory cell accumulation in pulmonary tissue. Administration of LTE decreased the expression of cyclooxygenase2 and matrix metalloproteinase-9 in mice exposed to ASD with the decline in p65 phosphorylation. Additionally, administration of LTE significantly elevated hemeoxygenase (HO)-1 expression in the pulmonary tissue of mice exposed to ASD. These results were consistent with the data of network pharmacological analysis. This experiment showed that LTE attenuated pulmonary inflammation caused by ASD via inhibition of NF-κB and elevation of HO-1. Therefore, LTE may have potential as a therapeutic agent to treat pulmonary inflammation caused by ASD.

Predictors of high-intensity care at the end of life among older adults with solid tumors: A population-based study.

INTRODUCTION: High-intensity end-of-life (EoL) care can be burdensome for patients, caregivers, and health systems and does not confer any meaningful clinical benefit. Yet, there are significant knowledge gaps regarding the predictors of high-intensity EoL care. In this study, we identify risk factors associated with high-intensity EoL care among older adults with the four most common malignancies, including breast, prostate, lung, and colorectal cancer. MATERIALS AND METHODS: Using SEER-Medicare data, we conducted a retrospective analysis of Medicare beneficiaries aged 65 and older who died of breast, prostate, lung, or colorectal cancer between 2011 and 2015. We used multivariable logistic regression to identify clinical, demographic, socioeconomic, and geographic predictors of high-intensity EoL care, which we defined as death in an acute care hospital, receipt of any oral or parenteral chemotherapy within 14 days of death, one or more admissions to the intensive care unit within 30 days of death, two or more emergency department visits within 30 days of death, or two or more inpatient admissions within 30 days of death. RESULTS: Among 59,355 decedents, factors associated with increased likelihood of receiving high-intensity EoL care were increased comorbidity burden (odds ratio [OR]:1.29; 95% confidence interval [CI]:1.28-1.30), female sex (OR:1.05; 95% CI:1.01-1.09), Black race (OR:1.14; 95% CI:1.07-1.23), Other race/ethnicity (OR:1.20; 95% CI:1.10-1.30), stage III disease (OR:1.11; 95% CI:1.05-1.18), living in a county with >1,000,000 people (OR:1.23; 95% CI:1.16-1.31), living in a census tract with 10%-<20% poverty (OR:1.09; 95% CI:1.03-1.16) or 20%-100% poverty (OR:1.12; 95% CI:1.04-1.19), and having state-subsidized Medicare premiums (OR:1.18; 95% CI:1.12-1.24). The risk of high-intensity EoL care was lower among patients who were older (OR:0.98; 95% CI:0.98-0.99), lived in the Midwest (OR:0.69; 95% CI:0.65-0.75), South (OR:0.70; 95% CI:0.65-0.74), or West (OR:0.81; 95% CI:0.77-0.86), lived in mostly rural areas (OR:0.92; 95% CI:0.86-1.00), and had poor performance status (OR:0.26; 95% CI:0.25-0.28). Results were largely consistent across cancer types. DISCUSSION: The risk factors identified in our study can inform the development of new interventions for patients with cancer who are likely to receive high-intensity EoL care. Health systems should consider incorporating these risk factors into decision-support tools to assist clinicians in identifying which patients should be referred to hospice and palliative care.

Focused active learning for histopathological image classification.

Active Learning (AL) has the potential to solve a major problem of digital pathology: the efficient acquisition of labeled data for machine learning algorithms. However, existing AL methods often struggle in realistic settings with artifacts, ambiguities, and class imbalances, as commonly seen in the medical field. The lack of precise uncertainty estimations leads to the acquisition of images with a low informative value. To address these challenges, we propose Focused Active Learning (FocAL), which combines a Bayesian Neural Network with Out-of-Distribution detection to estimate different uncertainties for the acquisition function. Specifically, the weighted epistemic uncertainty accounts for the class imbalance, aleatoric uncertainty for ambiguous images, and an OoD score for artifacts. We perform extensive experiments to validate our method on MNIST and the real-world Panda dataset for the classification of prostate cancer. The results confirm that other AL methods are 'distracted' by ambiguities and artifacts which harm the performance. FocAL effectively focuses on the most informative images, avoiding ambiguities and artifacts during acquisition. For both experiments, FocAL outperforms existing AL approaches, reaching a Cohen's kappa of 0.764 with only 0.69% of the labeled Panda data.

pH-Responsive Nanogels Generated by Polymerization-Induced Self-Assembly of a Succinate-Functional Monomer.

Colloidal nanogels formed from a pH-responsive poly(succinate)-functional core and a poly(sulfonate)-functional corona were prepared via a previously unreported reversible addition-fragmentation chain-transfer (RAFT)-mediated aqueous emulsion polymerization-induced self-assembly (PISA) route. Specifically, a poly(potassium 3-sulfopropyl methacrylate) (PKSPMA50) macromolecular chain-transfer agent (macro-CTA) was synthesized via RAFT solution polymerization followed by chain-extension with a hydrophobic, carboxylic acid-functional, 2-(methacryloyloxy) ethyl succinate (MES) monomer at pH 2. Colloidal nanoparticles with tunable diameters between 66 to 150 nm, depending on the core composition, and narrow particle size distributions were obtained at 20% w/w solids. Well-defined pH-responsive nanogels that swell on increasing the pH could be prepared even without the addition of a cross-linking comonomer, and introducing an additional cross-linker to the core led to smaller nanogels with lower swelling ratios. These nanogels could reversibly change in size on cycling the pH between acidic and basic conditions and remain colloidally stable over a wide pH range and at 70 °C.