Interacting collagen and tannic acid Particles: Uncovering pH-dependent rheological and thermodynamic behaviors.

HYPOTHESIS: Biomaterials such as collagen and tannic acid (TA) particles are of interest in the development of advanced hybrid biobased systems due to their beneficial therapeutic functionalities and distinctive structural properties. The presence of numerous functional groups makes both TA and collagen pH responsive, enabling them to interact via non-covalent interactions and offer tunable macroscopic properties. EXPERIMENT: The effect of pH on the interactions between collagen and TA particles is explored by adding TA particles at physiological pH to collagen at both acidic and neutral pH. Rheology, isothermal titration calorimetry (ITC), turbidimetric analysis and quartz crystal microbalance with dissipation monitoring (QCM-D) are used to study the effects. FINDINGS: Rheology results show significant increase in elastic modulus with an increase in collagen concentration. However, TA particles at physiological pH provide stronger mechanical reinforcement to collagen at pH 4 than collagen at pH 7 due to the formation of a higher extent of electrostatic interaction and hydrogen bonding. ITC results confirm this hypothesis, with larger changes in enthalpy, |ΔH|, observed when collagen is at acidic pH and |ΔH| > |TΔS| indicating enthalpy-driven collagen-TA interactions. Turbidimetric analysis and QCM-D help to identify structural differences of the collagen-TA complexes and their formation at both pH conditions.

Interfacial Contributions in Nanodiamond-Reinforced Polymeric Fibers.

We study the interfacial energy parameters that explain the reinforcement of polymers with nanodiamond (ND) and the development of mechanical strength of electrospun ND-reinforced composites. Thermodynamic parameters such as the wettability ratio, work of spreading and dispersion/aggregation transition are used to derive a criterion to predict the dispersibility of carboxylated ND (cND) in polymeric matrices. Such a criterion for dispersion (Dc) is applied to electrospun cND-containing poly(vinyl alcohol) (PVA), polyacrylonitrile (PAN), and polystyrene (PS) fiber composites. The shifts in glass transition temperature (ΔTg), used as a measure of polymer/cND interfacial interactions and hence the reinforcement capability of cNDs, reveal a direct correlation with the thermodynamic parameter Dc in the order of PAN < PS < PVA. Contrary to expectation, however, the tensile strength of the electrospun fibers correlates with the Dc and ΔTg only for semicrystalline polymers (PAN < PVA) while the amorphous PS displays a maximum reinforcement with cND. Such conflicting results reveal a synergy that is not captured by thermodynamic considerations alone but also factor in the contributions of polymer/cND interface stress transfer efficiency. Our findings open the possibility for tailoring the interfacial interactions in polymer-ND fiber composites to achieve maximum mechanical reinforcement.

Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing.

Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) of metastatic lung cancer was performed using 49 clinical biopsies obtained from 30 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNA-seq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell-state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap-junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNA-seq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes.

Modelling the impact of past and future climate scenarios on streamflow in a highly mountainous watershed: A case study in the West Seti River Basin, Nepal.

Hydrological model parameters are important during representation of the hydrological characteristics of a watershed. The West Seti River Basin (WSRB), a prominent Himalayan Basin of Nepal, is a major source of fresh water in the western region of the country. We used the Soil and Water Assessment Tool (SWAT) for hydrological modelling and identified the most sensitive hydrological parameters, while the Sequential Uncertainty Fitting (SUFI-2) technique was employed for model calibration. The model was calibrated for the study period (1999-2005) with a three-year warm-up period (1996-1998). Subsequently, it was validated for three years (2006-2008). The results show that the large number of Hydrological Response Units (HRUs) for model simulation took a considerable time, without improving the performance statistics. Importantly, significant improvements were observed during both calibration and validation periods when elevation bands (EBs) were taken into consideration. The p-factor, r-factor, coefficient of determination (R2), Nash-Sutcliffe efficiency (NSE), percent bias (PBIAS), Root mean square error (RMSE)-observations, and standard deviation (STDEV) ratio (RSR) were used to measure the performance between observed and simulated values. The values of p-factor, r-factor, R2, NSE, PBIAS, and RSR during the calibration were 0.82, 0.80, 0.84, 0.82, 7.2, and 0.42, respectively, whereas during validation they were 0.79, 0.72, 0.83, 0.82, 11.8, and 0.42, respectively. The calibrated model was then used to assess the anticipated river discharge. This study used four regional climate models (RCMs) for precipitation and six for temperature, together with their arithmetical average as multi-model ensembles (MMEs) under two representative concentration pathways (RCPs). We analysed the changes in precipitation, temperature, and river discharge for three future time frames: Future1 (F1: 2020-2044), Future2 (F2: 2045-2069), and Future3 (F3: 2075-2099) with respect to the baseline (1996-2005). The magnitude of changes varied according to the different climate models and warming scenarios. In general, the MMEs showed slightly increasing precipitation (higher during the F2 period), significantly increasing temperature (continuous rising trend), and moderately increasing river discharge (higher during the F2 period). Information such as the anticipated shift in the flow duration curve may be helpful to stakeholders across different water sectors for effective water resource management in the future. From the modelling perspective, the results show greater significance for EBs than HRUs during the modelling of high mountain basins with SWAT. This take-home message would be useful to hydrologists and other stakeholders in evaluating different scenarios over a short duration, without iteratively spending higher computational time.

Expanding the Teaching Toolbox: Characterizing Utility of a Web-Based Lecture Series in Educating Future Colleagues and Referrers about the Field of IR.

Opportunities for interventional radiology (IR) education and exposure remain limited at medical institutions without a local IR presence, thereby excluding a medical student population with potential to pursue careers in IR or become referring providers to IR. The purpose of this study was to evaluate the efficacy of a Webinar-based IR elective as an educational tool for outreach to US medical schools lacking local preclinical IR exposure. Our early results indicate that a Webinar-based IR lecture series can serve as an effective method for educating future physicians about the field of IR and when to consult IR for patient management.

Integrated assessment of the climate and landuse change impact on hydrology and water quality in the Songkhram River Basin, Thailand.

The livelihoods of people in the Songkhram River Basin (SRB) rely heavily on river water, especially those involved in the fisheries. Extensive landuse changes in SRB have raised concerns regarding its impacts in water quality in addition to the looming climate change effects. More importantly there is lack of detailed studies on landuse and climate change impact on river water quality for the sustainable water management. Therefore, this study aimed at quantifying the individual and integrated impact of climate and landuse change in streamflows and nitrate nitrogen loadings in the Songkhram River. Future streamflow was simulated using Soil and Water Assessment Tool (SWAT) whereas future climate projections were derived from three Regional Climate Models (RCMs) under two Representative Concentration Pathways (RCPs). A dynamic, spatially explicit, land use change model (Dyna-CLUE) was used to generate two future land use change scenarios namely economic and conservation scenarios. The results show that in future climate change is to be responsible for a 19.5 and 24% decrease in streamflow and 11.25 and 15.25% decrease in nitrate nitrogen loading as projected under RCP 4.5 and 8.5 scenarios, respectively. Whereas landuse change is found to be responsible for a 5.30 and 6.35% increase in streamflow and an 11 and 11.60% decrease in nitrate nitrogen loading under economic and conservation scenarios, respectively in future. Thus, in conjunction, these two agents are seen to play against each other, creating a net effect of decreased future streamflow (16% on average); whereas, in the case of nitrate nitrogen loading, the two work in tandem, leading to an amplified reduction (24.50% on average). Although landuse change is found to be the less afflicting agent, its role should not be overlooked-it may very well further exacerbate the situation if there is a greater unfavourable climatic variation than projected.

Imaging Predictors of Elevated Lung Shunt Fraction in Patients Being Considered for Yttrium-90 Radioembolization.

PURPOSE: To identify imaging findings associated with elevated lung shunt fraction (LSF) in patients being considered for yttrium-90 ((90)Y) radioembolization. MATERIALS AND METHODS: During the period 2009-2014, 152 consecutive patients underwent planning hepatic arteriography with technetium-99m ((99m)Tc) macroaggregated albumin (MAA) injection. Computed tomography (CT) or magnetic resonance imaging performed before the procedure for each patient was assessed for hepatic vein (HV) tumor thrombus or occlusion from external compression by tumor. When imaging was a multiphase CT scan (117 patients), the arterial phase was evaluated for evidence of early HV opacification (relative to unaffected HVs), indicating hepatic venous shunting. These factors were correlated with LSF determined by (99m)Tc-MAA imaging. RESULTS: Median LSF was 6.7% (range, < 0.1%-71%), significantly higher for HCC (8.0% vs 6.3% for other tumors, P = .048). Larger tumor size was associated with higher LSF in univariate analysis (P = .001). There was high interobserver agreement for determining hepatic venous shunting (97%, κ = 0.847), which was associated with higher LSF (P < .001; 78% sensitivity, 93% specificity). Of 5 cases of HV tumor thrombus, all had high (> 20%) LSF (P < .001). HV occlusion was also associated with higher LSF (P = .039). Multivariate analysis confirmed that early HV opacification and either HV tumor thrombus or occlusion were associated with higher LSF. CONCLUSIONS: Early HV opacification and HV tumor thrombus or occlusion on cross-sectional imaging performed before radioembolization are associated with elevated LSF, which may contraindicate or limit the dose delivered in (90)Y radioembolization. This information could be helpful during patient counseling for anticipating the most appropriate mode of liver-directed therapy.

Caval penetration by retrievable inferior vena cava filters: a retrospective comparison of Option and Günther Tulip filters.

PURPOSE: To compare the frequency of vena caval penetration by the struts of the Option and Günther Tulip cone filters on postplacement computed tomography (CT) imaging. MATERIALS AND METHODS: All patients who had an Option or Günther Tulip inferior vena cava (IVC) filter placed between January 2010 and May 2012 were identified retrospectively from medical records. Of the 208 IVC filters placed, the positions of 58 devices (21 Option filters, 37 Günther Tulip filters [GTFs]) were documented on follow-up CT examinations obtained for reasons unrelated to filter placement. In cases when multiple CT studies were obtained after placement, each study was reviewed, for a total of 80 examinations. Images were assessed for evidence of caval wall penetration by filter components, noting the number of penetrating struts and any effect on pericaval tissues. RESULTS: Penetration of at least one strut was observed in 17% of all filters imaged by CT between 1 and 447 days following placement. Although there was no significant difference in the overall prevalence of penetration when comparing the Option filter and GTF (Option, 10%; GTF, 22%), only GTFs showed time-dependent penetration, with penetration becoming more likely after prolonged indwelling times. No patient had damage to pericaval tissues or documented symptoms attributed to penetration. CONCLUSIONS: Although the Günther Tulip and Option filters exhibit caval penetration at CT imaging, only the GTF exhibits progressive penetration over time.

Body mass index and the risk of obesity in coeliac disease treated with the gluten-free diet.

BACKGROUND: Coeliac disease is increasingly diagnosed and weight changes are common after adoption of a gluten-free diet (GFD), however data on body mass index (BMI) changes are limited. AIM: To assess changes in BMI after diagnosis in a large coeliac population. METHODS: A total of 1018 patients with biopsy confirmed coeliac disease seen at our centre were studied retrospectively. Initial and follow-up BMIs were recorded, as was GFD adherence as assessed by an expert dietitian. RESULTS: A total of 679 patients with at least two recorded BMIs and GFD adherence data were included in the study. Mean follow-up was 39.5 months. Compared to regional population data, the coeliac cohort was significantly less likely to be overweight or obese (32% vs. 59%, P < 0.0001). Mean BMI increased significantly after GFD initiation (24.0 to 24.6; P < 0.001). 21.8% of patients with normal or high BMI at study entry increased their BMI by more than two points. CONCLUSIONS: Individuals with coeliac disease have lower BMI than the regional population at diagnosis. BMI increases on the GFD, especially in those that adhere closely to the GFD. On the GFD, 15.8% of patients move from a normal or low BMI class into an overweight BMI class, and 22% of patients overweight at diagnosis gain weight. These results indicate that weight maintenance counselling should be an integral part of coeliac dietary education.

Noncoeliac enteropathy: the differential diagnosis of villous atrophy in contemporary clinical practice.

BACKGROUND: Duodenal villous atrophy (DVA) is a key diagnostic finding in coeliac disease (CD). However, the differential diagnosis for this finding is broad. AIM: To identify conditions causing noncoeliac enteropathy (NCE) with villous atrophy and methods to differentiate between CD and NCE in clinical practice. METHODS: Through record review we identified patients with DVA due to conditions other than CD. Patient demographics, clinical features and relevant investigations were compared with CD patients. Rates of CD misdiagnosis, and response to treatments were recorded. RESULTS: Thirty cases of NCE were identified with ten different aetiologies. Unspecified immune-mediated enteropathy was the most common aetiology; affecting 10 patients. Gastrointestinal symptoms were more common in NCE than those in CD patients (P < 0.01). Twenty of the 24 NCE patients tested were HLA-DQ2/DQ8 negative. Twenty-six NCE patients were negative for IgA tissue transglutaminase (tTG) (P = 0.0001). Intraepithelial lymphocytosis was absent in 10 (33.3%) patients. Twenty-one NCE patients initially misdiagnosed with CD and one with gluten intolerance were prescribed a gluten free diet (GFD). Fifteen of 22 had repeat biopsy and none showed histological improvement. CONCLUSIONS: Although coeliac disease is the most common cause of DVA, noncoeliac enteropathy is not rare and may easily be mistaken for coeliac disease. Noncoeliac enteropathy is suggested by a normal initial tTG (87%), lack of intraepithelial lymphocytosis on biopsy, and lack of histological response to a gluten free diet. Subjective response to gluten free diet has poor predictive value for coeliac disease. Noncoeliac enteropathy can often be confirmed by negative HLA-DQ2/DQ8 testing and targeted investigations can ascertain a definitive aetiology in most cases.