bluuebunny/crossref_metadata_2025 huggingface dataset:
How low can we go with the dialysate flow? A retrospective study on the safety and adequacy of a water-saving dialysis prescription
Authors: Rydzewska-Rosołowska Alicja , Głowińska Irena , Kakareko Katarzyna , Pietruczuk Adam , Hryszko Tomasz
Published: August 2024

Background

Green nephrology encompasses all initiatives in kidney care that have a positive impact on climate and environment. To prepare the dialysate, at least 120 L of water are needed for one 4-h session with a dialysate flow (Qd) set at 500 mL/min. A lower dialysate flow rate is associated with a significant reduction in the amount of water used. The aim of this study was to check whether change of Qd from 500 mL/min to 300 mL/min has a significant impact on dialysis adequacy.

Methods

The study was a retrospective analysis. Due to administrative issues, a satellite dialysis center reduced their dialysate flow to 300 mL/min for a month. The center then increased Qd to 500 mL/min again. We analyzed laboratory data from 3 months before dialysate flow reduction, in the month with Qd reduced to 300 mL/min, and from 3 months thereafter with Qd set at 500 mL/min.

Results

Twenty-four people were included in the final analysis. There were no significant changes in urea reduction ratio caused by lower rate of Qd [64.50 (61.75–71.00) vs 67.00 (63.00–72.25) vs 69.00 (63.75–72.25), analysis of variance F(2,46) = 0.71, P = .50]. Similarly, hemodialysis adequacy expressed by Kt/V did not differ at any Qd [1.23 (1.12–1.41) vs 1.25 (1.18–1.40) vs 1.35 (1.19–1.48), ANOVA F(2,46) = 2.51, P = .09]. There was a small but statistically significant increase in mean predialysis potassium with lower Qd [potassium = 5.18 (95% confidence interval, 95% CI, 4.96–5.44) vs 5.46 (95% CI 5.23–5.69) vs 5.23 (95% CI 4.99–5.47) mmol/L at Qd = 500, 300 and 500 mL/min, respectively, P = .039].

Conclusion

Reduction in dialysate flow rate to 300 mL/min seems safe and does not cause any short-term negative effects in this small study. Thus, we might be able to achieve a similar therapeutic effect while saving water consumption. Larger, long-term studies incorporating patient-reported outcome measures are needed to confirm the efficacy of this approach.
DHCL-BR: Dual Hypergraph Contrastive Learning for Bundle Recommendation
Authors: Zhang Peng , Niu Zhendong , Ma Ru , Zhang Fuzhi
Published: August 2024

As an extension of conventional top-K item recommendation solution, bundle recommendation has aroused increasingly attention. However, because of the extreme sparsity of user-bundle (UB) interactions, the existing top-K item recommendation methods suffer from poor performance when applied to bundle recommendation. While some graph-based approaches have been proposed for bundle recommendation, these approaches primarily leverage the bipartite graph to model the UB interactions, resulting in suboptimal performance. In this paper, a dual hypergraph contrastive learning model is proposed for bundle recommendation. First, we model the direct and indirect UB interactions as hypergraphs to represent the higher-order UB relations. Second, we utilize the hypergraph convolution networks to learn the user and bundle embeddings from the hypergraphs, and improve the learned embeddings through a bidirectional contrastive learning strategy. Finally, we adopt a joint loss that combines the InfoBPR loss supporting multiple negative samples and the contrastive losses to optimize model parameters for prediction. Experiments on the real-world datasets indicate that our model performs better than the state-of-the-art baseline methods.
Burden of Bowel Urgency in Patients With Ulcerative Colitis and Crohn’s Disease: A Real-World Global Study
Authors: Atreya Raja , Redondo Isabel , Streit Petra , Protic Marijana , Hartz Susanne , Gurses Gamze , Knight Hannah , Barlow Sophie , Harvey Niamh , Hunter Gibble Theresa
Published: August 2024

Background

Bowel urgency is a highly disruptive and bothersome symptom experienced by patients with inflammatory bowel diseases (IBD), (ulcerative colitis [UC], and Crohn’s disease [CD]). However, the burden of bowel urgency among patients with varying experiences in targeted treatment has not been consistently assessed. This real-world study explored the clinical and health-related quality of life burden of bowel urgency among patients with IBD with differing treatment experiences.

Methods

This cross-sectional survey included gastroenterologists and their patients with IBD across France, Germany, Italy, Spain, the United Kingdom, and the United States treated for over 3 months. Physicians provided patient demographics, clinical characteristics, and treatment history. Patients reported their health-related quality of life and work productivity. Patients with UC and CD were analyzed separately and stratified into 3 groups: Targeted therapy naïve, those receiving their first-line targeted therapy, and targeted therapy experienced.

Results

This study found that 17%-26% of UC and 13%-17% of CD patients experienced persistent bowel urgency, irrespective of receiving conventional or targeted therapy. Moreover, patients with bowel urgency experienced an increased clinical and health-related quality of life burden compared to patients without bowel urgency, which physicians most commonly regarded as one of the most difficult symptoms to treat, with the burden remaining substantial irrespective of their treatment experience.

Conclusions

Despite several current treatment options, new therapeutic strategies are necessary to provide relief from bowel urgency, one of the most challenging symptoms for people living with IBD.
Dietary oxyclozanide influences antioxidant enzyme activities and damages DNA in Galleria mellonella (Lepidoptera: Pyralidae)
Authors: Çelik Cihat , Stanley David , Büyükgüzel Ender
Published: August 2024

Oxyclozanide (OXY) is an anthelmintic widely used in the treatment of flatworm infection and fasciolosis. It also has antiadenovirus, antibiofilm, antifungal, and antibacterial activities. Various chemicals have been suggested as alternative chemicals in insect pest management. Here, the oxidative and genotoxic effects of OXY on 7th instars, pupae and adults of the model organism Galleria mellonella (Linnaeus) (Lepidoptera: Pyralidae) were examined. First-instar larvae were reared on 0.003, 0.03, 0.3, and 1.5 g OXY per 100 g artificial diets. Compared with all tested OXY concentrations and controls without OXY, dietary OXY led to increased antioxidant capacity and genotoxic effects. Concentrations of malondialdehyde, an oxidative stress marker, were significantly increased in adults of larvae reared on OXY-charged diets at 0.3 and 1.5 g/100 g compared to the adult control group. We also recorded a significant increase in the genotoxic test data (Tail length, Tail DNA %, Tail moment) at the same stages and concentrations. We recorded significant increases in glutathione-S-transferase, superoxide dismutase (SOD) and glutathione peroxidase activities in larvae fed high OXY concentrations. SOD and catalase activities were also significantly increased at the concentration of 0.03 g/100 g of OXY in the pupal and adult stages. Cytochrome P450 monooxygenase activity was significantly increased at the highest concentration of OXY in the larval and pupal stages. Also, our regression analysis indicates a correlation between the markers of oxidative stress, antioxidant enzymes and comet parameters. These data indicate that OXY induces oxidative stress and antioxidative enzyme response.
Predicting early-stage coronary artery disease using machine learning and routine clinical biomarkers improved by augmented virtual data
Authors: Koloi Angela , Loukas Vasileios S , Hourican Cillian , Sakellarios Antonis I , Quax Rick , Mishra Pashupati P , Lehtimäki Terho , Raitakari Olli T , Papaloukas Costas , Bosch Jos A , März Winfried , Fotiadis Dimitrios I
Published: August 2024

Aims

Coronary artery disease (CAD) is a highly prevalent disease with modifiable risk factors. In patients with suspected obstructive CAD, evaluating the pre-test probability model is crucial for diagnosis, although its accuracy remains controversial. Machine learning (ML) predictive models can help clinicians detect CAD early and improve outcomes. This study aimed to identify early-stage CAD using ML in conjunction with a panel of clinical and laboratory tests.

Methods and results

The study sample included 3316 patients enrolled in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. A comprehensive array of attributes was considered, and an ML pipeline was developed. Subsequently, we utilized five approaches to generating high-quality virtual patient data to improve the performance of the artificial intelligence models. An extension study was carried out using data from the Young Finns Study (YFS) to assess the results’ generalizability. Upon applying virtual augmented data, accuracy increased by approximately 5%, from 0.75 to –0.79 for random forests (RFs), and from 0.76 to –0.80 for Gradient Boosting (GB). Sensitivity showed a significant boost for RFs, rising by about 9.4% (0.81–0.89), while GB exhibited a 4.8% increase (0.83–0.87). Specificity showed a significant boost for RFs, rising by ∼24% (from 0.55 to 0.70), while GB exhibited a 37% increase (from 0.51 to 0.74). The extension analysis aligned with the initial study.

Conclusion

Accurate predictions of angiographic CAD can be obtained using a set of routine laboratory markers, age, sex, and smoking status, holding the potential to limit the need for invasive diagnostic techniques. The extension analysis in the YFS demonstrated the potential of these findings in a younger population, and it confirmed applicability to atherosclerotic vascular disease.
Colchicine in acutely decompensated heart failure: the COLICA trial
Authors: Pascual-Figal Domingo , Núñez Julio , Pérez-Martínez Maria T , González-Juanatey José Ramón , Taibo-Urquia Mikel , Llàcer-Iborra Pau , Delgado Juan , Villar Sandra , Mirabet Sonia , Aimo Alberto , Riquelme-Pérez Alejandro , Anguita-Sánchez Manuel , Martínez-Sellés Manuel , Noguera-Velasco Jose A , Ibáñez Borja , Bayés-Genís Antoni
Published: August 2024

Background and Aims

Acute heart failure (AHF) promotes inflammatory activation, which is associated with worse outcomes. Colchicine has proven effective in other cardiovascular conditions characterized by inflammatory activation, but has never been evaluated in the setting of AHF.

Methods

This multicenter, randomized, double-blind, and placebo-controlled trial included patients with AHF, requiring ≥40 mg of intravenous furosemide, regardless of their left ventricular ejection fraction (LVEF) and inpatient or outpatient setting. Patients were randomized within the first 24 h of presentation to receive either colchicine or placebo, with loading dose of 2 mg, followed by 0.5 mg every 12 h for 8 weeks.

Results

A total of 278 patients [median age 75 years, LVEF 40%, baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) 4262 pg/mL] were randomized to colchicine (n = 141) or placebo (n = 137). The primary endpoint, the time-averaged reduction in NT-proBNP levels at 8 weeks, did not differ between the colchicine group [−62.2%, 95% confidence interval (CI) −68.9% to −54.2%] and the placebo group (−62.1%, 95% CI −68.6% to −54.3%) (ratio of change 1.0). The reduction in inflammatory markers was significantly greater with colchicine: ratio of change 0.60 (P < .001) for C-reactive protein and 0.72 (P = .019) for interleukin-6. No differences were found in new worsening heart failure episodes (14.9% with colchicine vs. 16.8% with placebo, P = .698); however, the need for intravenous furosemide during follow-up was lower with colchicine (P = .043). Diarrhea was slightly more common with colchicine, but it did not result in differences in medication withdrawal (8.5% vs. 8.8%).

Conclusions

Colchicine was safe and effective in reducing inflammation in patients with AHF; however, colchicine and placebo exhibited comparable effects on reducing NT-proBNP and preventing new worsening heart failure events.
Challenges of accreditation in forensic fields concerned with human identification: a survey of European facial examiners
Authors: Obertová Zuzana , Siebke Inga , Schüler Grit
Published: August 2024

Forensic anthropology and forensic facial image identification are areas with two aspects in common: (i) the use of anthropological knowledge concerning human variation in their analyses and (ii) low numbers of accredited forensic units. While the low numbers are often explained by the uniqueness of human identification cases, given the high level of scrutiny in the forensic sciences, interest in and efforts to achieve accreditation have become increasingly prominent. Therefore, this study aimed to obtain accreditation-relevant information about the working environment in facial image comparison units by surveying facial examiners across Europe. Two surveys were distributed: One was given to participants of a European Commission-funded training course for technical assessors in facial image comparison, and the second, more comprehensive survey, was distributed to members of the European Network of Forensic Science Institutes Digital Imaging Working Group. Thirty-four responses from facial examiners from 16 countries were received. All respondents worked for a governmental organization, nine (26.5%) in accredited units, and 12 (35.3%) had worked as facial examiners for more than 11 years. More than 80% of respondents had an academic background. All examiners from accredited units reported having standard operating procedures, annual Digital Imaging Working Group proficiency testing, and using a standard methodology (compared with 72%, 92%, and 84% from nonaccredited units, respectively). The survey found that working conditions in forensic facial image identification vary among European countries. Some respondents from nonaccredited units reported that their unit had no standard operating procedures, with proficiency tests and intralaboratory validations not performed regularly, and an inconsistently used standard methodology. As these conditions are typically required for successful accreditation, a better understanding of best practice and accreditation requirements in the field is needed. Facilitating interactions between forensic practitioners and quality managers may prove beneficial for future accreditation efforts.

Key points
A large-scale in vivo screen to investigate the roles of human genes in Drosophila melanogaster
Authors: Avila Ashley , Paculis Lily , Tascon Roxana Gonzalez , Ramos Belen , Jia Dongyu
Published: August 2024

Understanding the signaling pathways in which genes participate is essential for discovering the etiology of diseases in humans. The model organism, Drosophila melanogaster, has been crucial in understanding the signaling pathways in humans, given the evolutionary conservation of a significant number of genes between the two species. Genetic screens using Drosophila are a useful way of testing large number of genes to study their function and roles within signaling pathways. We conducted a large-scale genetic screen to identify which human genes cause an alteration in the morphology of the Drosophila eye. The GMR-Gal4 was employed to activate a single UAS-human gene in the eye tissue. In total, we screened 802 UAS-human gene stocks, corresponding to 787 human protein-coding genes, for the ability to influence eye development. We found that overexpression of 64 human genes were capable of disrupting eye development, as determined by phenotypic changes in eye texture, size, shape, bristle morphology, and ommatidia organization. Subsequent analysis revealed that the fly genome encodes proteins that are homologous to a majority of the 64 human genes, raising the possibility that overexpression of these transgenes altered eye development by altering the activity of evolutionarily conserved developmental signaling pathways. Consistent with this hypothesis, a secondary screen demonstrated that overexpression of fly homologs produced phenotypes that mimicked those produced by overexpression of the human gene. Our screening has identified 64 human genes capable of inducing phenotypes in the fly, offering a foundation for ongoing research aimed at understanding functionally conserved pathways across species.
Subsurface stress assessment from cross-coupled borehole acoustic eigenmodes
Authors: Jørgensen Ole , Burns Dan
Published: August 2024

We present an approach, based on cross-coupling of quadrupole and monopole borehole acoustic modes caused by anisotropy, to investigate the in situ stress state, a critical parameter for effective CO2 sequestration and for determining subsurface injection bounds in general. We focus on in situ stress states where the vertical direction is a principal stress direction, and we aim at determining the minimum and maximum horizontal stresses. Because of non-linear elastic effects, three unequal principal stresses in an otherwise isotropic rock may create three orthogonal planes of symmetry, which characterize an orthorhombic elastic medium. Near a wellbore, where the stress field is perturbed, a stress sensitive material causes material axes and moduli to form a spatial distribution to which sonic logging is sensitive. We present a method for differentiating between stress induced and intrinsic anisotropy. Using finite element modelling, we demonstrate that in either case the quadrupole fundamental mode includes an axis-symmetric (monopole) component. We demonstrate that the acoustic amplitude at the borehole centre divided by the maximum acoustic amplitude at the wellbore periphery (dominated by the acoustic profile $\cos(2\theta )$) is an indicator of elastic anisotropy. We denote this ratio $I_A$ and argue that $I_A\gt 0$ when the elastic anisotropy is of entirely intrinsic origin (meaning the elastic moduli are in-sensitive to stress), and further that $I_A$ increases for decreasing frequency for such cases. We demonstrate that $I_A$ attains negative values for increasing frequency in stress-sensitive formations where a cross-over (from negative to positive values) is attributed to the perturbed velocity/moduli/stress fields near the wellbore. In synthetic data, we show that the ratio $I_A$, in combination with the phase velocity dispersion, uniquely determines the state of stress in stress-sensitive formations. In stress in-sensitive formations, we argue that $I_A$ at lower frequencies, that is at frequencies slightly above the cut-off frequency, is very sensitive to elastic anisotropy. We argue that in quadrupole eigenmodes, evidence of intrinsic anisotropy is present at low frequencies whereas stress induced anisotropy is better gauged at moderate to high frequencies. Finally, we discuss the practical implications of these findings.
Morphological and genetic characterization of the muscadine fruit abscission zone
Authors: Brinley Alana R , Conner Patrick J , Yu Fahong , Sarkhosh Ali , Liu Tie
Published: August 2024

Muscadines face limitations to fresh market production due to high manual labor costs. Mechanical harvesting holds promise for reducing the costs associated with muscadine production but requires cultivars with easily detached fruit at maturity. This study aimed to determine muscadine fruit and pedicel characteristics influencing fruit detachment force (FDF) and to unravel the genes, hormones, and regulatory networks governing muscadine abscission. We characterized the FDF of muscadine fruit across 18 genotypes and at four developmental stages. Following this, we performed a transcriptome analysis using the mature pedicel tissue of two genotypes, a genotype with high FDF at maturity and a genotype with low FDF at maturity, to identify differentially expressed and uniquely expressed genes contributing to fruit detachment. We found that pedicel length, pedicel–fruit junction area, and fruit diameter positively correlated with FDF. This study also identified novel candidate genes, transcription factor families, and pathways associated with muscadine fruit abscission. These findings provide valuable knowledge on the progression of fruit abscission and insights for reducing FDF, particularly in developing machine-harvestable muscadine cultivars and fostering sustainability and efficiency in muscadine production.
Brain mGlu5 Is Linked to Cognition and Cigarette Smoking but Does Not Differ From Control in Early Abstinence From Chronic Methamphetamine Use
Authors: McClintick Megan N , Kessler Robert M , Mandelkern Mark A , Mahmoudie Tarannom , Allen Daicia C , Lachoff Hilary , Pochon Jean-Baptiste F , Ghahremani Dara G , Farahi Judah B , Partiai Edwin , Casillas Robert A , Mooney Larissa J , Dean Andy C , London Edythe D
Published: August 2024

Background

The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance.

Methods

Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested.

Results

MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus.

Conclusion

Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.
Quality criteria and certification for paediatric oncology centres: an international cross-sectional survey
Authors: Schladerer Sarah P , Otth Maria , Scheinemann Katrin
Published: August 2024

Quality criteria and certification possibilities for paediatric oncology centres vary between countries and are not widely used. An overview of the type and how quality criteria and certifications are used in countries with highly developed healthcare systems is missing. This international cross-sectional survey investigated the use of quality criteria for paediatric oncology centres and whether certification is possible. We sent an online survey to paediatric oncologists from 32 countries worldwide and analysed the survey results and provided regional or national documents on quality criteria and certification possibilities descriptively. Paediatric oncologists from 28 (88%) countries replied. In most countries, the paediatric oncology centres were partly or completely grown historically (75%), followed by the development based on predefined criteria (29%), and due to political reason (25%), with more than one reason in some countries. Quality criteria are available in 20 countries (71%). We newly identified or specified five quality criteria, in addition to those from a previously performed systematic review. Certification of paediatric oncology centres is possible in 13 countries (46%), with a specific certification for paediatric oncology in seven, and a mandatory certification in three of them. The use of quality criteria and certification possibilities are heterogeneous, with quality criteria being more frequently used than certifications. Our study provides an overview of country-specific documents and links with quality criteria, and centre certification possibilities. It can serve as a reference document for stakeholders and may inform an international harmonization of quality criteria and centre certification between countries with similar healthcare systems.
Optimal dosing regimen of caspofungin in adolescents with allogeneic haematopoietic stem cell transplantation
Authors: Du Bin , Zhang Wei , Wang Yang , Wu Yue-E , Zhang Ya-Hui , van den Anker John , Hao Guo-Xiang , Zhao Wei
Published: August 2024

Objectives

The optimal dosing regimen of caspofungin in adolescents undergoing allogeneic haematopoietic stem cell transplantation against Candida spp. is unknown. The study aimed to compare body surface area (BSA)-based and fixed dosing regimens through population pharmacokinetic (PPK) analysis and to optimize dosing regimens likely to achieve therapeutic exposures.

Methods

Opportunistic sampling was used to collect plasma concentrations through a prospective observational pharmacokinetic study. PPK analysis and Monte Carlo simulations (n = 1000) were performed using NONMEM.

Results

A total of 86 samples of 30 adolescents (12–17 years old) were best described by a two-compartment pharmacokinetic model. BSA is the only covariate on clearance and central volume of distribution. For Candida glabrata and Candida albicans, a standard dosing regimen could achieve at least a 90% probability of target attainment for the indicator of AUC0–24/MIC90. Dosing regimen simulations identified a BSA cut-off value of 1.3 m2, where a fixed loading dose (LD) is preferred when BSA ≥ 1.3 m2 and a BSA-based LD is preferred when BSA < 1.3 m2. For maintenance dose (MD), however, the BSA-based dose was proposed, regardless of BSA. The current maximum dosing regimen of LD 70 mg/day and MD 70 mg/day could not result in sufficient antifungal exposure for Candida parapsilosis with MIC90 of 1 mg/L. Furthermore, an LD of 70 mg/day and MD of 60 mg/m2/day rendered 90.4% steady-state trough concentration (Ctrough) over 1 mg/L in the virtual population.

Conclusions

Our study proposed optimized dosing regimens of caspofungin based on AUC0–24/MIC90 or Ctrough, which may support further individualized treatment.
Feeding or pen surface application of clinoptilolite with different particle sizes: impact on nitrogen utilization and manure ammonia emissions in feedlot cattle
Authors: Myers Cheyanne A , de Haro Marti Mario E , Chahine Mireille , Chibisa Gwinyai E
Published: August 2024

This study investigated the effects of feeding clinoptilolite (CLN; 2.5% of diet dry matter) with a particle size of either 30- or 400-µm on ruminal fermentation characteristics, measures of nitrogen (N) utilization, and manure ammonia-N (NH3) emissions in feedlot cattle. The impact of directly applying 30- or 400-µm CLN to the pen surface (2,250 kg/ha) on manure NH3–N emissions was also evaluated. Six beef heifers were used in a replicated 3 × 3 Latin square design with 21-d periods. Dietary treatments were 1) finishing ration with no supplement (CON), 2) CON + 30-µm CLN (CLN-30), and 3) CON + 400-µm CL (CLN-400). Intake was measured daily. To evaluate fermentation characteristics, ruminal fluid was collected on day 19. Indwelling pH loggers were used to measure ruminal pH from days 15 to 21. Blood was collected 3-h post-feeding on day 21 for metabolite analysis. Fecal grab and urine spot samples were also collected from days 19 to 21 to measure nutrient digestibility, route of N excretion, and in vitro NH3 emissions. There was no diet effect (P ≥ 0.12) on nutrient intake and apparent total tract digestibility, and ruminal short-chain fatty acid profile and pH. Ruminal NH3 concentration, which was lower (P = 0.04) for CLN-30 than CON heifers, did not differ between CON and CLN-400 heifers. Although there was no diet effect (P = 0.50) on plasma urea-N (PUN) concentration, proportion of urea-N excreted in urine was lower (P = 0.01) for CLN-30 than CON and CLN-400 heifers. Urinary NH3–N excretion, which was greater (P ≤ 0.04) for CLN-400 than CON heifers, did not differ between CLN-30 and CLN-400 heifers. Feeding CLN also increased (P ≤ 0.02) fecal excretion of potassium (K) and iron (Fe) and reduced (P = 0.01) urinary excretion of calcium (Ca). There was a treatment × time interaction (P = 0.01) for NH3 emission rate, which was greatest within the first 36 h of incubation and was lower for manure from CLN-400 compared to CON and CLN-30 heifers and pen surface application treatments. Cumulative NH3 emissions were lower (P < 0.01) for manure from CLN-400 compared to CON and CLN-30 heifers and the pen surface application treatments. Although surface application was ineffective, feeding 400-µm CLN to finishing cattle could result in a beneficial decrease in manure NH3 emissions. However, changes in fecal and urine excretion of minerals like K and Ca, which suggest a decrease in bioavailability, need to be considered when feeding CLN in finishing cattle diets.
Multi-omics analyses reveal aberrant differentiation trajectory with WNT1 loss-of-function in type XV osteogenesis imperfecta
Authors: Tan Zhijia , Chen Peikai , Zhang Jianan , Shek Hiu Tung , Li Zeluan , Zhou Xinlin , Zhou Yapeng , Yin Shijie , Dong Lina , Feng Lin , Wong Janus Siu Him , Gao Bo , To Michael Kai Tsun
Published: August 2024

Osteogenesis imperfecta (OI) is a group of severe genetic bone disorders characterized by congenital low bone mass, deformity, and frequent fractures. Type XV OI is a moderate to severe form of skeletal dysplasia caused by WNT1 variants. In this cohort study from southern China, we summarized the clinical phenotypes of patients with WNT1 variants and found that the proportion of type XV patients was around 10.3% (25 out of 243) with a diverse spectrum of phenotypes. Functional assays indicated that variants of WNT1 significantly impaired its secretion and effective activity, leading to moderate to severe clinical manifestations, porous bone structure, and enhanced osteoclastic activities. Analysis of proteomic data from human skeleton indicated that the expression of SOST (sclerostin) was dramatically reduced in type XV patients compared to patients with COL1A1 quantitative variants. Single-cell transcriptome data generated from human tibia samples of patients diagnosed with type XV OI and leg-length discrepancy, respectively, revealed aberrant differentiation trajectories of skeletal progenitors and impaired maturation of osteocytes with loss of WNT1, resulting in excessive CXCL12+ progenitors, fewer mature osteocytes, and the existence of abnormal cell populations with adipogenic characteristics. The integration of multi-omics data from human skeleton delineates how WNT1 regulates the differentiation and maturation of skeletal progenitors, which will provide a new direction for the treatment strategy of type XV OI and relative low bone mass diseases such as early onset osteoporosis.
Longitudinal course of circulating miRNAs in a patient with hypophosphatasia and asfotase alfa treatment: a case report
Authors: Hadzimuratovic Benjamin , Haschka Judith , Hackl Matthias , Diendorfer Andreas B , Mittelbach Andreas , Feurstein Julia , Zwerina Jochen , Resch Heinrich , Kocijan Roland
Published: August 2024

Hypophosphatasia (HPP) is characterized by low activity of tissue nonspecific alkaline phosphatase (TNSALP). The enzyme replacement therapy asfotase alfa has been approved for childhood-onset forms of HPP. MicroRNAs (miRNAs) have emerged as a novel disease biomarker, with potential application in therapy monitoring. Circulating miRNAs were analyzed at baseline, months 1, 2, 4, and 16 in a 49-yr-old woman with childhood-onset HPP, chronic musculoskeletal pain, and non-traumatic fractures prior to enzyme replacement therapy. Serum RNA was extracted and sequenced using miRNeasy Mini Kit (Qiagen, Germany), RealSeq Biosciences Kit (Santa Cruz, US) together with miND spike-in control kit (TAmiRNA, Austria) and Illumina NovaSeq 6000 SP1 flow cell (San Diego, US). Brief Pain Inventory Severity and Interference scores (BPI-S/BPI-I), fatigue severity scale (FSS), Patient Global Impression of Improvement (PGI-I), Western Ontario and McMaster university hip disability and osteoarthritis outcome score (WOMAC), fibromyalgia impact questionnaire (FIQ), 6-Minute Walking Test (6-MWT), chair-rise-test (CRT), and handgrip dynamometry (HD) were performed at baseline and different timepoints during the therapy. Out of >800 screened, 84 miRNAs were selected based on differences in expression profiles between 24 HPP patients and 24 healthy controls. Six miRNAs showed a clear graphic trend and were up- or downregulated by ≥50% reads per million (rpm). These included hsa-let-7i-5p (+50%), hsa-miR-1-3p (−66.66%), hsa-miR-1294 (+63.63%), hsa-miR-206 (−85.57%), hsa-miR-375-3p (−71.43%), and hsa-miR-624-5p (+69.44%). hsa-miR-1-3p and hsa-miR-206 were identified as muscle-specific miRNAs. hsa-mir-375-3p, which negatively regulates osteogenesis, was significantly downregulated. In terms of patient-reported outcomes, BPI-S, BPI-I, FSS, PGI-I, WOMAC, and FIQ showed a reduction by −58.62%, −68.29%, −33.33%, −75.00%, −63.29%, and −43.02%, respectively. 6-MWT improved by +33.89% and CRT by −44.46%. Mean hand grip strength of the right/left hand measured by HD improved by +12.50% and + 23.53%, respectively. miRNA profile changes during the therapy with asfotase alfa, accompanying improvements in functionality tests and quality of life scores.
Contemporary epidemiology of hepatocellular carcinoma: understanding risk factors and surveillance strategies
Authors: Jaber Fouad , Cholankeril George , El-Serag Hashem B
Published: August 2024

The contemporary epidemiology of hepatocellular carcinoma (HCC) shows a shift in the main etiological risk factors from less common but highly virulent (eg, hepatitis C and B) to more common but weak risk factors (eg, alcohol and metabolic syndrome). Therefore, we are in a seemingly paradoxical state of declining overall incidence rates of HCC-related to improved prevention and treatment of viral hepatitis but burgeoning number of people at an elevated risk of HCC. Several geographic regions have reported an increase in HCC attributable to alcoholic liver disease and metabolic dysfunction associated with steatotic liver disease (MASLD). The importance of risk stratification is increasing to allow for targeted prevention and early detection of HCC. Most risk factors predispose HCC through the formation of cirrhosis, which has served as the main risk stratifying factor. However, this scheme is showing cracks at both ends of the spectrum. On one hand, the risk of developing HCC varies widely among patients with contemporary advanced fibrosis or cirrhosis, and on the other hand up to one-third of MASLD-related HCC occurs among patients with no clear evidence of cirrhosis. The use of multidimensional (eg, clinical, epidemiological, and biochemical) predictive algorithms may improve risk stratification efforts. The shift in HCC risk factors also further heightened the importance and limitations of current surveillance practices (eg, reduced performance of ultrasound in MASLD). Therefore, exploring advanced imaging methods, new biomarkers but also existing combinations of biomarkers augmented by clinical factors for HCC early detection is crucial.
Oven-drying and decontamination effects on crude protein concentration and in vitro crude protein digestibility of yellow mealworm (Tenebrio molitor) (Coleoptera: Tenebrionidae)
Authors: Gómez-Oquendo Giovanna , Loza Puerta Andrés , Gonzales Gutierrez Cesar , Gómez-Bravo Carlos A , Salazar-Cubillas Khaterine
Published: August 2024

The study aims to assess the impact of oven-drying and decontamination on crude protein concentration and in vitro crude protein digestibility of yellow mealworms. Two kilograms of 12-wk-old mealworm larvae were subjected to freezing prior to the drying process. Approximately 1.5 kg of mealworm larvae were divided into 3 groups and exposed to oven-drying at temperatures of 50 °C for 36 h, 60 °C, and 70 °C for 24 h each. At intervals of 2 h, sets of 3 replicates were withdrawn to record water loss. Consistent weight stabilization was observed at 36 h for 50 °C (T50), 18 h for 60 °C (T60), and 14 h for 70 °C (T70). The remaining 0.5 kg of mealworm larvae was divided and dried under treatments T50, T60, and T70. Each treatment was then split into 2 portions, with one portion subjected to 90 °C for 15 min (denoted as T50-90, T60-90, T70-90) to eliminate microbial contamination. The 6 treatments were then used to determine concentrations of dry matter, crude ash, crude protein, pre-caecal protein digestibility, and dry matter residues after neutral detergent fiber, acid detergent fiber, and acid detergent lignin treatments. No interaction was observed between drying and decontamination treatments (P > 0.17). Pre-caecal crude protein digestibility increased with decreasing temperature (T50: 58% crude protein; T60: 51% crude protein; T70: 50% crude protein). Therefore, lower temperatures for longer times preserve crude protein digestibility. These findings are crucial for understanding how drying temperature and time impact protein bioavailability.
Non-tariff barriers to trade
Authors: Leonardi Marco , Meschi Elena
Published: August 2024

Prior to the recent resurgence prompted by the US–China trade war, tariffs on international trade had been consistently diminishing over the past few decades. In response, advanced countries increasingly turned to non-tariff measures (NTMs) to protect their industries from foreign competition. In this article, we exploit a novel database on NTMs to investigate their impact on the labor market in the United States. We use the political importance of an industry, measured by its employment share in swing states during presidential elections, as an instrumental variable for NTM protection. Our results suggest that NTMs mitigate the adverse employment effects resulting from exposure to Chinese import competition, but exert a negative influence on manufacturing wages, particularly for skilled workers.
Leveraging Selective State Capacity: Understanding Changing Responses to Migration and Refugees
Authors: Norman Kelsey P
Published: August 2024

State capacity is seen as one of the central elements determining whether countries have “strong” or “weak” systems of immigration and asylum. An underlying assumption of the global refugee regime is that countries of the Global South—thought to have less state capacity—do not have the ability to respond and host asylum seekers and refugees and must be financially supported by countries of the Global North in order to do so. But how can we understand “strong” migration responses from an otherwise “weak” state, as well as responses that change over time without corresponding alterations to underlying state capacity? This paper analyzes the case of Egypt, which, over the course of a decade, alternated between three types of migration policies requiring a range of state resources. Drawing on more than 70 in-person interviews and an analysis of public documents, this paper presents a theory of selective state capacity and argues that infrastructural weakness does not imply a lack of strategic decision-making in the field of migration, or an unwillingness to expend state resources, when the political incentives are in place.
Computational analysis of Carreau fluid flow in presence with buoyancy force, viscous dissipation, and chemical reaction
Authors: Ullah Hameed , Awan Farah Jabeen , Maqbool Khadija , Lu Dianchen
Published: August 2024

This study presents the computational analysis of heat and mass transfer of an in-compressible electrically conducting non-Newtonian Carreau fluid flow in the presence of buoyancy forces, viscous dissipation, chemical reaction, and heat source/sink. Mathematical modeling is made subject to an inclined disk, which is linearly stretching and also momentum, thermal, and concentration boundary layer are used to simplify laws of fluid mechanics. A similarity transformation is implied to convert the governing system of PDE's into system of ordinary differential equations and numerical solution is obtained by the Software Matlab. The impact of pertinent parameters involved in the velocity, temperature, and concentration profiles are shown through graphs and the results for Sherwood number, skin friction, and Nusselt number are demonstrated through the tables.
Employing user-centered design to develop a remote technology kit for studying young children’s social communication skills
Authors: Petruccelli Marisa , Howard Mya , Morelos Andres , Wainer Allison , Broder-Fingert Sarabeth , Ingersoll Brooke , Stone Wendy L , Carter Alice S
Published: August 2024

Objective

The COVID-19 pandemic required behavioral researchers to rapidly pivot to the implementation of remote study protocols to facilitate data collection. Remote implementation required robust and flexible research protocols including reliable audio/visual technology that met all the quality, security, and privacy hallmarks of lab-based equipment, while also being portable and usable by nontechnical staff and participants. The project’s primary purpose was to develop a technology kit that could be deployed for data collection in homes with young children. The secondary objective was to determine the feasibility of the kit for use longitudinally across four disparate sites.

Method

User-centered design principles were employed in the development and implementation of a technology kit deployed across urban, suburban, and rural participant locations in four states. Preliminary feasibility and usability data were gathered to determine the reliability of the kit across three timepoints.

Results

In study 1, a technology kit was constructed addressing all project needs including the provision of the internet to connect remotely with participants. Staff training protocols and participant-facing materials were developed to accompany deployment procedures. In study 2, data gathered in technology logs demonstrated successful capturing of video footage in 96% of opportunities with most technology challenges mitigated. Subsequent behavioral coding indicated 100% of captured assessment footage has been successfully coded to date. Moreover, participants needed less support for technology setup at their later timepoints, and staff rated the kit as highly usable.

Conclusion

This study offers a model for future development of technology use in remote community- and home-based pediatric research.
Severity scores, damage indices, and the concept of the colchicine-resistant patient in familial Mediterranean fever
Authors: Er Ozan , Akay Helin , Ozgozen Mehmet Emre , Gulhan Didem , Ugurlu Serdal
Published: August 2024

Familial Mediterranean fever is a common autoinflammatory disease. The primary treatment is colchicine; however, 5–10% of patients do not respond to colchicine and are considered colchicine resistant. Colchicine resistance and disease severity are highly associated, with each used to assess and define the other. In our review, we examined the most commonly used severity scores, damage indices, and definitions of colchicine resistance, revealing both shortcomings and advantages for each. We emphasize the necessity for a new severity score that integrates the definition of colchicine resistance.
Determination of global DNA methylation level by methylation-sensitive comet assay in patients with urinary bladder cancer
Authors: Kocak Ozer , Kankaya Selin , Kalender Goktug , Citgez Sinharib , Onal Bulent , Dincer Yildiz
Published: August 2024

DNA methylation is an important mechanism in the regulation of gene expression and maintenance of genomic integrity. Aberrant DNA methylation is an early event in carcinogenesis. DNA methyltransferase inhibitors are used to restore aberrant DNA methylation and inhibit tumor growth. Evaluation of DNA methylation level is important for an effective anti-cancer therapy. In the present study, the determination of global DNA methylation levels in patients with urinary bladder cancer was proposed. The methylation-sensitive comet assay determined the global DNA methylation level at the level of single cells. McrBC enzyme, a methylation-sensitive restriction endonuclease, was used for enzymatic digestion to generate additional breaks at methylated sites. % DNA methylation level was significantly higher in patients with bladder cancer compared to the control group. The clinical performance of % DNA methylation analysis by methylation-sensitive comet assay was evaluated by ROC curve. Using the cutoff value of 6.5% DNA methylation, 92% sensitivity, and 42% specificity were obtained. In conclusion, global DNA methylation measured by methylation-sensitive comet assay may be a promising noninvasive biomarker that reduces interventional tests required in the diagnosis and follow-up of urinary bladder cancer.
Discovery of antiphage systems in the lactococcal plasmidome
Authors: Grafakou Andriana , Mosterd Cas , Beck Matthias H , Kelleher Philip , McDonnell Brian , de Waal Paul P , van Rijswijck Irma M H , van Peij Noël N M E , Cambillau Christian , Mahony Jennifer , van Sinderen Douwe
Published: August 2024

Until the late 2000s, lactococci substantially contributed to the discovery of various plasmid-borne phage defence systems, rendering these bacteria an excellent antiphage discovery resource. Recently, there has been a resurgence of interest in identifying novel antiphage systems in lactic acid bacteria owing to recent reports of so-called ‘defence islands’ in diverse bacterial genera. Here, 321 plasmid sequences from 53 lactococcal strains were scrutinized for the presence of antiphage systems. Systematic evaluation of 198 candidates facilitated the discovery of seven not previously described antiphage systems, as well as five systems, of which homologues had been described in other bacteria. All described systems confer resistance against the most prevalent lactococcal phages, and act post phage DNA injection, while all except one behave like abortive infection systems. Structure and domain predictions provided insights into their mechanism of action and allow grouping of several genetically distinct systems. Although rare within our plasmid collection, homologues of the seven novel systems appear to be widespread among bacteria. This study highlights plasmids as a rich repository of as yet undiscovered antiphage systems.
Discovery of numerous novel Helitron-like elements in eukaryote genomes using HELIANO
Authors: Li Zhen , Gilbert Clément , Peng Haoran , Pollet Nicolas
Published: August 2024

Helitron-like elements (HLEs) are widespread eukaryotic DNA transposons employing a rolling-circle transposition mechanism. Despite their prevalence in fungi, animals, and plant genomes, identifying Helitrons remains a formidable challenge. We introduce HELIANO, a software for annotating and classifying autonomous and non-autonomous HLE sequences from whole genomes. HELIANO overcomes several limitations of existing tools in speed and accuracy, demonstrated through benchmarking and its application to the complex genomes of frogs (Xenopus tropicalis and Xenopus laevis) and rice (Oryza sativa), where it uncovered numerous previously unidentified HLEs. In an extensive analysis of 404 eukaryote genomes, we found HLEs widely distributed across phyla, with exceptions in specific taxa. HELIANO’s application led to the discovery of numerous new HLEs in land plants and identified 20 protein domains captured by certain autonomous HLE families. A comprehensive phylogenetic analysis further classified HLEs into two primary clades, HLE1 and HLE2, and revealed nine subgroups, some of which are enriched within specific taxa. The future use of HELIANO promises to improve the global analysis of HLEs across genomes, significantly advancing our understanding of this fascinating transposon superfamily.