Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of starch sources varying in particle sizes on ruminal fermentation, nutrient flow, starch digestibility, and lactation performance of dairy cows

Abstract Cereal grains are the predominant starch source (SS) for dairy cows; however, starch digestibility varies greatly depending on source, grain processing, and potentially interactions between these factors. The objective was to study the effects of the interactions between SS, and particle sizes (PS) on ruminal fermentation, nutrient flow, starch digestibility, and lactation performance of dairy cows. Four ruminally cannulated multiparous Holstein cows were used in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Two SS (corn or sorghum) used in this study were either finely or coarsely ground (using a 1- or 4-mm screen sieve). Digesta flow was quantified using the reticular sampling technique, applying the triple-marker method. Data were analyzed using the GLIMMIX procedure of SAS version 9.3 (SAS Institute Inc., Cary, NC, USA). For ruminal pH, data were analysed with time as repeated measure. There were no interactions between SS and PS on production or intake, flow, and digestibility of nutrients. Dry matter intake was greater for the corn diet compared to the sorghum diet (25.15 vs. 21.98 kg/d), which consequently affected nutrient intake, however, PS did not affect intake. Milk yield was not affected by SS; however, it was greater for cows fed fine grains than cows fed coarser grains (25.32 vs. 23.16 kg/d). Milk fat and milk protein were not affected by SS or PS. Interactions (SS × PS) were observed for ruminal pH, reticular pH, and volatile fatty acids (VFA) concentrations but not for ruminal NH3–N concentration. Ruminal and reticular pH were greater for sorghum when coarsely ground and the total VFA concentration was decreased, compared to coarse corn and fine sorghum; however, coarsely grinding corn did not affect ruminal or reticular pH nor VFA concentration. Acetate concentration was lower for corn when finely ground; however, finely grinding sorghum did not affect acetate. Decreasing PS increased ruminal digestibility of starch (87.18% vs. 83.43%), reduced the flow of starch to the reticulum (0.79 vs. 0.96 kg/d) but decreased neutral detergent fiber digestibility in the rumen (30.23% vs. 34.88%). Although SS were differently affected by processing, the effects of PS on production, intake, flow, and digestibility of nutrients were observed regardless of the SS. Furthermore, the effects of decreasing PS on pH and VFA concentrations were more pronounced in sorghum compared to corn.
Ulcerative colitis and periodontitis – a cross-sectional pilot study from a Norwegian cohort

Abstract Background Inflammatory bowel disease, which includes ulcerative colitis (UC), is an inflammatory disorder with potential impact on periodontal disease, but evidence to date for this association is limited. The primary aim of this study was to investigate the prevalence of periodontitis according to the 2017-classification in a cohort of subjects with UC. The secondary aim was to assess a potential correlation of periodontal status with previous UC disease parameters and to assess oral health-related quality-of-life. Method A cohort from a community hospital in Norway with confirmed extensive UC was comprehensively examined. Periodontal parameters, OHIP-14 and demographic variables were collected. Previous UC data including colon activity index (CAI), Mayo score and years of UC diagnosis was used to explore a potential correlation with periodontal status. Results A total of 50 out of 63 invited patients participated. According to the 2017-classification, 74% of the patients presented periodontitis. No correlation was found between periodontitis (stage, grade, bleeding on probing or probing pocket depth ≥6mm) and CAI, Mayo score, or years with UC diagnosis. Conclusions Within the limitations of this study, the prevalence of periodontitis among patients with mild UC for more than 12 years was in line with that reported from a Norwegian general population. No correlation between periodontitis and UC disease indices or years with UC diagnosis was observed. The study suggests that the susceptibility to periodontitis may be limited in patients with well treated or mild UD who regularly attend the dental office, despite a considerable UC disease duration.
Injectable cell-laden hydrogels fabricated with cellulose and chitosan nanofibers for bioprinted liver tissues

Bio-based hydrogels as three-dimensional (3D) constructs have attracted attention in advanced tissue engineering. Compared with conventional two-dimensional (2D) cell culture, cells grown in 3D scaffolds are expected to demonstrate the inherent behavior of living organisms of cellular spheroids. Herein, we constructed cell-laden nanofiber-based hydrogels in combination with 2,2,6,6-tetramethylpiperidine 1-oxyl-oxidized cellulose nanofiber (TOCNF) and chitosan nanofiber (CsNF) for bioadaptive liver tissue engineering. The carboxylates of TOCNF and amines of CsNF were directly crosslinked via EDC/NHS chemistry. The rheological properties of the solutions for the nanofibers and hydrogels revealed sufficient physical properties for the injection, printing, and plotting process, as well as significant encapsulation of living cells. As-designed hydrogels exhibited excellent viscoelastic properties with typical shear-thinning behavior, and had a storage modulus of 1234 Pa ± 68 Pa, suitable for cell culture. Non-cytotoxicity was confirmed using a live/dead assay with mouse-derived fibroblast NIH/3T3 cells. Human hepatocellular carcinoma HepG2 cells could be cultured on a gel surface (2D environment) and encapsulated in the gel structure (3D environment), which enabled 10 d growth with high gene expression level of albumin of HepG2 spheroids in the 3D gels. The biodegradable cell-laden hydrogels are expected to mimic the cellular microenvironment and provide potential for bioadaptive 3D cell cultures in biomedical applications.
Intravascular Imaging Use in Percutaneous Coronary Interventions of Chronic Total Occlusions.

BACKGROUND Intravascular ultrasound (IVUS) can assist percutaneous coronary intervention (PCI) of chronic total occlusions (CTO). METHODS We analyzed 8,983 CTO PCIs performed in 8,771 patients between 2012 and 2022 at 39 centers. RESULTS Overall, IVUS was used in 44.5% of the cases, for crossing in 11.5% and for stent optimization in 33.1%. IVUS for stent optimization was used more often for complex lesions with higher prevalence of calcification (51.2% vs 34.3%; P<.001); was associated with lower air kerma radiation dose (1.78 [1.00, 3.09] vs 2.30 (1.35, 3.91) min, P<. 001) and contrast volume (190 [138, 258] vs 220 [160, 300] ml, P<.001). Among cases with successful guidewire crossing, those that used IVUS for stent optimization had higher technical (99.3% vs 96.3%; P<.001) and procedural (96.1% vs 94.6%, P=.002) success rates and similar major adverse complication event rates (2.04% vs 1.62%; P=.176). The use of IVUS for stent optimization significantly increased over time. CONCLUSION In a contemporary, multicenter registry, IVUS was used in 44.5% and its use for stent optimization significantly increased over time. Cases where IVUS was used for stent optimization had higher technical and procedural success and similar risk of complications compared with cases where IVUS was not used for stent optimization.
Progress in the Quantitative Assessment of Transporter-Mediated Drug–Drug Interactions Using Endogenous Substrates in Clinical Studies

Variations in drug transporter activities, caused by genetic polymorphism and drug–drug interactions (DDIs), alter the systemic exposure of substrate drugs, leading to differences in drug responses. Recently, some endogenous substrates of drug transporters, particularly the solute carrier family transporters such as OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, and MATE2-K, have been identified to investigate variations in drug transporters in humans. Clinical data obtained support their performance as surrogate probes in terms of specificity and reproducibility. Pharmacokinetic parameters of the endogenous biomarkers depend on the genotypes of drug transporters and the systemic exposure to perpetrator drugs. Furthermore, the development of physiologically based pharmacokinetic models for the endogenous biomarkers has enabled a top-down approach to obtain insights into the effect of perpetrators on drug transporters and to more precisely simulate the DDI with victim drugs, including probe drugs. The endogenous biomarkers can address the uncertainty in the DDI prediction in the preclinical and early phases of clinical development and have the potential to fulfill regulatory requirements. Therefore, the endogenous biomarkers should be able to predict disease effects on the variations in drug transporter activities observed in patients. This mini-review focuses on recent progress in the identification and use of the endogenous drug transporter substrate biomarkers and their application in drug development. SIGNIFICANCE STATEMENT Advances in analytical methods have enabled the identification of endogenous substrates of drug transporters. Changes in the pharmacokinetic parameters (Cmax, AUC, or CLR) of these endogenous biomarkers relative to baseline values can serve as a quantitative index to assess variations in drug transporter activities during clinical studies and thereby provide more precise DDI predictions.
Replacement of soybean oil by Hermetia illucens larvae fat in broiler diets alters the breast muscle lipidome and reduces lipid oxidation of the breast muscle during heat-processing

ABSTRACT Replacement of soybean oil by insect fat from Hermetia illucens (HI) has been reported to increase the proportions of saturated fatty acids (SFA) and decrease those of polyunsaturated fatty acids (PUFA) in total lipids of breast and thigh meat in broilers. Since the susceptibility of meat to oxidation is strongly dependent on its PUFA content, the present study hypothesised that replacement of soybean oil by HI larvae fat in broiler diets reduces the formation of lipid oxidation products, including oxidation products of cholesterol and phytosterols, in heat-processed breast muscle of broilers. To test this hypothesis, 100 male, 1-day-old Cobb 500 broilers were assigned to three groups and fed three different nutrient adequate diets, which varied only in the fat source (group HI-0: 0% HI larvae fat and 5% soybean oil; group HI-2.5: 2.5% HI larvae fat and 2.5% soybean oil; group HI-5.0: 5.0% HI larvae fat and 0% soybean oil), in a three-phase feeding system for 35 days. While the growth performance of the broilers was not different, the absolute and relative breast muscle weights were higher in group HI-5.0 than in group HI-0 (p < 0.05). The proportions of C12:0, C14:0, C14:1, C16:0, C16:1 and total SFA were higher and those of C18:1, C18:2 n-6, C18:3 n-3 and total PUFA were lower in breast muscle total lipids of group HI-5.0 than in groups HI-2.5 and HI-0 (p < 0.05). Lipidomic analysis of breast muscle revealed that the concentration of triacylglycerols was 46% and 53% lower in groups HI-2.5 and HI-5.0, respectively, than in group HI-0 (p < 0.05), whereas all other lipid classes detected did not differ among groups. Concentrations of thiobarbituric acid-reactive substances, 7α-hydroxycholesterol, 7β-hydroxycholesterol and total cholesterol oxidation products in heat-processed breast muscle were lower in group HI-5.0 than in group HI-0 (p < 0.05). Concentrations of oxidation products of phytosterols in heat-processed breast muscle were generally much lower than those of cholesterol oxidation products and did not differ between the three groups of broilers. In conclusion, complete replacement of soybean oil with HI larvae fat in broiler diets strongly alters the fatty acid composition of breast muscle total lipids and reduce lipid oxidation of the breast muscle during heat-processing.
Rendering Perceived Terrain Stiffness in VR Via Preload Variation Against Body-Weight

PreloadStep is a novel platform that creates the illusion of walking on different types of terrain in Virtual Reality without requiring users to wear any special instrumentation. PreloadStep works by compressing a set of springs between two plates, with the amount of compression determining the perceived stiffness of the virtual terrain. The platform can render perception of stiffness by applying preload forces up to 824 N in different portions of the terrain, capable of changing stiffness illusion even while a user is standing on it. The effectiveness of PreloadStep was tested in two perception studies (perception thresholds and haptic-visual congruence studies) and an example application, with the results indicating that it is a promising method for creating engaging virtual terrain experiences.
Post‐marketing safety concerns with nirmatrelvir: A disproportionality analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System

Nirmatrelvir is an antiviral drug with a novel mechanism of action, targeting the 3‐CL protease, and is used in the treatment of COVID‐19. However, the potential side effects have not yet been fully studied. The aim of this study was to identify potential safety signals of nirmatrelvir by analysing post‐marketing safety data based on the largest publicly available worldwide pharmacovigilance database.
Caring Knowledge as a Strategy to Mitigate Violence against Nurses: A Discussion Paper

Abstract Violence against nurses is a disturbing trend in healthcare that has reached epidemic proportions globally. These violent incidents can result in physical and psychological injury, exacerbating already elevated levels of stress and burnout among nurses, further contributing to absenteeism, turnover, and intent to leave the profession. To ensure the physical and mental well-being of nurses and patients, attention to the development of strategies to reduce violence against nurses must be a priority. Caring knowledge—rooted in the philosophy of care—is a potential strategy for mitigating violence against nurses in healthcare settings. We present what caring knowledge is, analyze its barriers to implementation at the health system and education levels and explore potential solutions to navigate those barriers. We conclude how the application of models of caring knowledge to the nurse-patient relationship has the potential to generate improved patient safety and increased satisfaction for both nurses and patients.
Optimization of Vaccine Responses in Solid Organ Transplant Recipients

Transplant recipients are at increased risk of severe acute respiratory syndrome- coronavirus 2 (SARS- CoV- 2) morbidity and mortality. In this issue, Meziyerh and colleagues 1 reported that higher exposures to mycophenolic acid measured by area under the curve (AUC) correlated with diminished quantitative antibody responses and seroconversion rates to mRNA- based coronavirus disease 2019 (COVID- 19)
Experiments on the flow past a circular cylinder at low Reynolds numbers

Part I describes measurements of the drag on circular cylinders, made by observing the bending of quartz fibres, in a stream with the Reynolds number range 0·5-100. Comparisons are made with other experimental values (which cover only the upper part of this range) and with the various theoretical calculations. Part II advances experimental evidence for there being a transition in the mode of the vortex street in the wake of a cylinder at a Reynolds number around 90. Investigations of the nature of this transition and the differences between the flows on either side of it are described. The interpretation that the change is between a vortex street originating in the wake and one originating in the immediate vicinity of the cylinder is suggested.
Evolution of guidelines for the management of hereditary angioedema due to C1 inhibitor deficiency.

Hereditary angioedema (HAE) is a severe and disabling condition characterized by recurrent episodes of subcutaneous or mucosal swelling in the skin, respiratory and gastrointestinal tracts. HAE due to C1-esterase inhibitor deficiency (C1-INH-HAE) is the most prevalent subtype. The present Iberian study compared C1-INH-HAE treatment guidelines/norms published between 2010 and 2022 to identify main differences regarding therapeutic approaches for on-demand treatment and short- and long-term prophylaxis (LTP). Globally, HAE guidelines evolved with the availability of new treatments and with a change in the management paradigm towards an individualized, patient-centered approach where quality of life (QoL) is central. In line with that, an increasing trend was observed towards home-based treatment, as it potentially facilitates timely interventions, provides greater flexibility and convenience, and is associated with increased QoL, enabling patients to lead more normal lives. LTP is the indication with most innovations over the years, concurrently with the availability of new therapies and awareness of patients' needs. Several prophylactic therapies with a high level of evidence became available, although formal head-to-head comparisons are lacking. The treatment goals became more ambitious, from a reduction in the frequency, severity, and duration of attacks to achieving total disease control and normalization of patients´ lives at present. Changes in terminology, such as the introduction of designations as 'first line", and the introduction of patient-reported outcome measures (PROM) to assess patients' perceptions of their self-experienced QoL and well-being, are also relevant and addressed in the document, together with still unmet needs in the management of C1-INH-HAE.
Cost-Effectiveness of Cell Salvage in Trauma Blood Transfusions

Introduction Despite the increasing amount of evidence supporting its use, cell salvage (CS) remains an underutilized resource in operative trauma care in many hospitals. We aim to evaluate the utilization of CS in adult trauma patients and associated outcomes to provide evidence-based recommendations. Methods A systematic review was conducted using PubMed, Google Scholar, and CINAHL. Articles evaluating clinical outcomes and the cost-effectiveness of trauma patients utilizing CS were included. The primary study outcome was mortality rates. The secondary outcomes included complication rates (sepsis and infection) and ICU-LOS. The tertiary outcome was the cost-effectiveness of CS. Results This systematic review included 9 studies that accounted for a total of 1119 patients that received both CS and allogeneic transfusion (n = 519), vs allogeneic blood transfusions only (n = 601). In-hospital mortality rates ranged from 13% to 67% in patients where CS was used vs 6%-65% in those receiving allogeneic transfusions only; however, these findings were not significantly different (P = .21-.56). Similarly, no significant differences were found between sepsis and infection rates or ICU-LOS in those patients where CS usage was compared to allogeneic transfusions alone. Of the 4 studies that provided comparisons on cost, 3 found the use of CS to be significantly more cost-effective. Conclusions Cell salvage can be used as an effective method of blood transfusion for trauma patients without compromising patient outcomes, in addition to its possible cost advantages. Future studies are needed to further investigate the long-term effects of cell salvage utilization in trauma patients.
Elevated expression of the AIM2 gene in response to Helicobacter pylori along with the decrease of NLRC4 inflammasome is associated with peptic ulcer development

Helicobacter Pylori (H. Pylori) cause peptic ulcer disease (PUD), but the inflammasome's role in PUD is not well understood. Therefore this study has investigated inflammasome compartment expression and IL‐1β production in gastritis (G) and peptic ulcer disease. This study was based on gene expression of inflammasome compartments on stomach biopsies of 50 patients with PUD as cases and 50 individuals with gastritis as controls. The expression of NLRC4, ASC, IL‐18, and serum IL‐1β decreased in the PUD group compared to the control group. AIM2 gene expression increased, and NLRP12 gene expression decreased in H. pylori‐seropositive positive (HP+) individuals compared to H. pylori‐seronegative (HP−) individuals. The G‐HP+ subjects had higher serum IL‐1β and AIM2 gene expression than G‐HP− subjects but lower NLRP3 and NLRP12 gene expression. The PUD‐HP+ had lower serum IL‐1β, but higher AIM2 and IL‐18 expression than PUD‐HP−. The PUD‐HP− patients had decreased IL‐18 expression than G‐HP− group. The PUD‐HP+ had lower serum IL‐1β and NLRC4 expression than G‐HP+, while NLRP1 and NLRP3 were higher in expression in PUD‐HP+. The expression of caspase‐1, NLRP3 and NAIP were correlated with IL‐1β and IL‐18. In conclusion, a decrease in NLRC4, IL‐18, ASC genes, and IL‐1β levels in PUD patients compared to gastritis may act in the development of PUD. H. pylori caused AIM2 induction and reduced NLRP12, indicating their contribution to bacterial responses. Decreased NLRC4 expression and IL‐1β protein, together with enhanced NLRP1, and NLRP3 expression, promotes H. pylori to develop peptic ulcers.
Increased cytokine levels induced by high phenylalanine concentrations in late diagnosis PKU patients compared to early diagnosis: Anti‐inflammatory effect of L‐carnitine

Phenylketonuria (PKU) was the first genetic disease to have an effective therapy, which consists of phenylalanine intake restriction. However, there are patients who do not adhere to treatment and/or are not submitted to neonatal screening. PKU patients present L‐carnitine (L‐car) deficiency, compound that has demonstrated an antioxidant and anti‐inflammatory role in metabolic diseases. This study evaluated the effect caused by exposure time to high Phe levels in PKU patients at early and late diagnosis, through pro‐ and anti‐inflammatory cytokines, as well as the L‐car effect in patients under treatment. It was observed that there was a decrease in phenylalanine levels in treated patients compared to patients at diagnosis, and an increase in L‐car levels in the patients under treatment. Inverse correlation between Phe versus L‐car and nitrate plus nitrite versus L‐car in PKU patients was also showed. We found increased proinflammatory cytokines levels: interleukin (IL)‐1β, interferons (IFN)‐gamma, IL‐2, tumor necrosis factor (TNF)‐alpha, IL‐8 and IL‐6 in the patients at late diagnosis compared to controls, and IL‐8 in the patients at early diagnosis and treatment compared to controls. Increased IL‐2, TNF‐alpha, IL‐6 levels in the patients at late diagnosis compared to early diagnosis were shown, and reduced IL‐6 levels in the treated patients compared to patients at late diagnosis. Moreover, it verified a negative correlation between IFN‐gamma and L‐car in treated patients. Otherwise, it was observed that there were increased IL‐4 levels in the patients at late diagnosis compared to early diagnosis, and reduction in treated patients compared to late diagnosed patients. In urine, there was an increase in 8‐isoprostane levels in the patients at diagnosis compared to controls and a decrease in oxidized guanine species in the treated patients compared to the diagnosed patients. Our results demonstrate for the first time in literature that time exposure to high Phe concentrations generates a proinflammatory status, especially in PKU patients with late diagnosis. A pro‐oxidant status was verified in not treated PKU patients. Our results demonstrate the importance of early diagnosis and prompt start of treatment, in addition to the importance of L‐car supplementation, which can improve cellular defense against inflammation and oxidative damage in PKU patients.