Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors influencing milk osteopontin concentration based on measurements from Danish Holstein cows

Abstract Our objective was to determine the content of the bioactive protein osteopontin (OPN) in bovine milk and identify factors influencing its concentration. OPN is expressed in many tissues and body fluids, with by far the highest concentrations in milk. OPN plays a role in immunological and developmental processes and it has been associated with several milk production traits and lactation persistency in cows. In the present study, we report the development of an enzyme linked immunosorbent assay (ELISA) for measurement of OPN in bovine milk. The method was used to determine the concentration of OPN in milk from 661 individual Danish Holstein cows. The median OPN level was determined to 21.9 mg/l with a pronounced level of individual variation ranging from 0.4 mg/l to 67.8 mg/l. Breeding for increased OPN in cow's milk is of significant interest, however, the heritability of OPN in milk was found to be relatively low, with an estimated value of 0.19 in the current dataset. The variation explained by the herd was also found to be low suggesting that OPN levels are not affected by farm management or feeding. Interestingly, the concentration of OPN was found to increase with days in milk and to decrease with parity.
Perspectives of Healthcare Professionals Toward Interprofessional Collaboration in Primary Care Settings in a Middle Eastern Country

Background Primary healthcare (PHC) setting is regarded as a central pillar to the healthcare system as it tends to be the first point of contact for patients. Interprofessional collaboration between healthcare professionals (HCP) in PHC settings remains unexplored in the Middle East. Aim The objective of this study was to explore the perspectives of HCP in PHC centers towards interprofessional collaboration and to identify the facilitators and the barriers to collaborative practice. Methods A cross-sectional, web- and paper-based survey involving HCP in PHC centers was conducted in Qatar. Descriptive statistics as well as Student’s t-test and One Way ANOVA test were performed to determine statistical differences in Readiness for Interprofessional Learning (RIPLs) scores between demographic groups. Results Overall, 1415 participants out of a potential 2500 HCP practicing in Qatar completed the survey (response rate, 56.6%). HCP generally indicated a positive attitude and readiness towards interprofessional collaboration. Furthermore, physicians had slightly more positive readiness towards understanding their professional identity than other healthcare professionals. Participants with previous interprofessional collaboration or interprofessional education experiences exhibited greater, but non-significant positive attitudes toward interprofessional collaboration compared to those without previous experiences. Identified barriers and facilitators included are conceptual rather than structural. Facilitating factors included HCP readiness and perceived benefit of interprofessional collaboration effectiveness in the work setting, increased professional satisfaction, respect between healthcare professions, appreciation of others’ contribution, leadership, and institutional support. Top perceived barriers included leadership and support, time commitment, and resources constraints. Conclusion HCP in PHC settings have demonstrated the willingness and readiness to engage in interprofessional collaboration. Recent reforms within the PHC setting consist of promoting interprofessional teams and collaborative culture. However, it is imperative to provide training and education to foster and support interprofessional collaborative practices.
Design of strongly modulating pulses to implement precise effective Hamiltonians for quantum information processing

We describe a method for improving coherent control through the use of detailed knowledge of the system’s Hamiltonian. Precise unitary transformations were obtained by strongly modulating the system’s dynamics to average out unwanted evolution. With the aid of numerical search methods, pulsed irradiation schemes are obtained that perform accurate, arbitrary, selective gates on multiqubit systems. Compared to low power selective pulses, which cannot average out all unwanted evolution, these pulses are substantially shorter in time, thereby reducing the effects of relaxation. Liquid-state nuclear magnetic resonance techniques on homonuclear spin systems are used to demonstrate the accuracy of these gates both in simulation and experiment. Simulations of the coherent evolution of a three-qubit system show that the control sequences faithfully implement the unitary operations, typically yielding gate fidelities on the order of 0.999 and, for some sequences, up to 0.9997. The experimentally determined density .
On information fraction for Fleming‐Harrington type weighted log‐rank tests in a group‐sequential clinical trial design

When comparing survival times of treatment and control groups under a more realistic nonproportional hazards scenario, the standard log‐rank (SLR) test may be replaced by a more efficient weighted log‐rank (WLR) test, such as the Fleming‐Harrington (FH) test. Designing a group‐sequential clinical trial with one or more interim looks during which a FH test will be performed, necessitates correctly quantifying the information fraction (IF). For SLR test, IF is defined simply as the ratio of interim to final numbers of events; but for FH test, it can deviate substantially from this ratio. In this article, we separate the effect of weight function (of FH test) alone on IF from the effect of censoring. We have shown that, without considering the effect of censoring, IF can be derived analytically for FH test using information available at the design stage and the additional effect due to censoring is relatively smaller. This article intends to serve two major purposes: first, to emphasize and rationalize the deviation of IF in weighted log‐rank test from that of SLR test which is often overlooked (Jiménez, Stalbovskaya, and Jones); second, although it is impossible to predict IF for a weighted log‐rank test at the design stage, our decomposition of effects on IF provides a reasonable and practically feasible range of IF to work with. We illustrate our approach with an example and provide simulation results to evaluate operating characteristics.
Discovery of Bacterial Fimbria–Glycan Interactions Using Whole-Cell Recombinant Escherichia coli Expression

Understanding the tropism of pathogens for host and tissue requires a complete understanding of the host receptors targeted by fimbrial adhesins. Furthermore, blocking adhesion is a promising strategy to counter increasing antibiotic resistance and is enabled by the identification of host receptors. ABSTRACT Chaperone-usher (CU) fimbriae are the most abundant Gram-negative bacterial fimbriae, with 38 distinct CU fimbria types described in Escherichia coli alone. Some E. coli CU fimbriae have been well characterized and bind to specific glycan targets to confer tissue tropism. For example, type 1 fimbriae bind to α-d-mannosylated glycoproteins such as uroplakins in the bladder via their tip-located FimH adhesin, leading to colonization and invasion of the bladder epithelium. Despite this, the receptor-binding affinity of many other E. coli CU fimbria types remains poorly characterized. Here, we used a recombinant E. coli strain expressing different CU fimbriae, in conjunction with glycan array analysis comprising >300 glycans, to dissect CU fimbria receptor specificity. We initially validated the approach by demonstrating the purified FimH lectin-binding domain and recombinant E. coli expressing type 1 fimbriae bound to a similar set of glycans. This technique was then used to map the glycan binding affinity of six additional CU fimbriae, namely, P, F1C, Yqi, Mat/Ecp, K88, and K99 fimbriae. The binding affinity was determined using whole-bacterial-cell surface plasmon resonance. This work describes new information in fimbrial specificity and a rapid and scalable system to define novel adhesin-glycan interactions that underpin bacterial colonization and disease. IMPORTANCE Understanding the tropism of pathogens for host and tissue requires a complete understanding of the host receptors targeted by fimbrial adhesins. Furthermore, blocking adhesion is a promising strategy to counter increasing antibiotic resistance and is enabled by the identification of host receptors. Here, we use a defined E. coli heterologous expression system to identify glycan receptors for six chaperone-usher fimbriae and identify novel receptors that are consistent with their known function. The same system was used to measure the kinetics of binding to the identified glycan, wherein bacterial cells were immobilized onto a biosensor chip and the interactions with glycans were quantified by surface plasmon resonance. This novel, dual-level analysis, where screening for the repertoire of glycan binding and the hierarchy of affinity of the identified ligands is determined directly from a natively expressed fimbrial structure on the bacterial cell surface, is superior in both throughput and biological relevance.
A metabolomic approach to identify the link between sports activity and atheroprotection.

AIMS Physical activity (PA) is a mainstay of cardiovascular prevention. This study aimed to identify metabolic mediators of PA that protect against the development of atherosclerosis. METHODS AND RESULTS A total of 2160 participants in the LIFE heart study were analysed with data on PA and vascular phenotyping. In a targeted metabolomic approach, 61 metabolites (amino acids and acylcarnitines) were measured using liquid chromatography-tandem mass spectrometry. We investigated the interactions between PA, metabolites and markers of atherosclerosis in order to uncover possible mediation effects. Intended sports activity, but no daily PA, was associated with a lower degree of atherosclerosis, odds ratio (OR) for total atherosclerotic burden of 0.76 (95% confidence interval 0.62-0.94), carotid artery plaque OR 0.79 (0.66-0.96), and peripheral artery disease OR 0.74 (0.56-0.98). Twelve amino acids, free carnitine, five acylcarnitines were associated with sports activity. Of these, eight metabolites were also associated with the degree of atherosclerosis. In the mediation analyses, a cluster of amino acids (arginine, glutamine, pipecolic acid, taurine) were considered as possible mediators of atheroprotection. In contrast, a group of members of the carnitine metabolism (free carnitine, acetyl carnitine, octadecenoyl carnitine) were associated with inactivity and higher atherosclerotic burden. CONCLUSION Our metabolomic approach, which is integrated into a mediation model, provides transformative insights into the complex metabolic processes involved in atheroprotection. Metabolites with antioxidant and endothelial active properties are believed to be possible mediators of atheroprotection. The metabolomic mediation approach can support the understanding of complex diseases in order to identify targets for prevention and therapy.
Amphioxus neuroglia: Molecular characterization and evidence for early compartmentalization of the developing nerve cord

Glial cells play important roles in the development and homeostasis of metazoan nervous systems. However, while their involvement in the development and function in the central nervous system (CNS) of vertebrates is increasingly well understood, much less is known about invertebrate glia and the evolutionary history of glial cells more generally. An investigation into amphioxus glia is therefore timely, as this organism is the best living proxy for the last common ancestor of all chordates, and hence provides a window into the role of glial cell development and function at the transition of invertebrates and vertebrates. We report here our findings on amphioxus glia as characterized by molecular probes correlated with anatomical data at the transmission electron microscopy (TEM) level. The results show that amphioxus glial lineages express genes typical of vertebrate astroglia and radial glia, and that they segregate early in development, forming what appears to be a spatially separate cell proliferation zone positioned laterally, between the dorsal and ventral zones of neural cell proliferation. Our study provides strong evidence for the presence of vertebrate‐type glial cells in amphioxus, while highlighting the role played by segregated progenitor cell pools in CNS development. There are implications also for our understanding of glial cells in a broader evolutionary context, and insights into patterns of precursor cell deployment in the chordate nerve cord.
Tumor Metabolism and Neurocognition in CNS Lymphoma.

BACKGROUND The mechanistic basis for neurocognitive deficits in CNS lymphoma and other brain tumors is incompletely understood. We tested the hypothesis that tumor metabolism impairs neurotransmitter pathways and neurocognitive function. METHODS We performed serial cerebrospinal fluid (CSF) metabolomic analyses using liquid chromatography-electrospray tandem mass spectrometry to evaluate changes in the tumor microenvironment in 14 patients with recurrent CNS lymphoma, focusing on 18 metabolites involved in neurotransmission and bioenergetics. These were paired with serial mini-mental state examinations (MMSE) and MRI studies for tumor volumetric analyses. Patients were analyzed in the setting of the phase I trial of lenalidomide/rituximab. Associations were assessed by Pearson and Spearman correlation coefficient. Generalized estimating equation (gee) models were also established, adjusting for within-subject repeated measures. RESULTS Of 18 metabolites, elevated CSF lactate correlated most strongly with lower MMSE score (p<8E-8, rho=-0.67). High lactate was associated with lower GABA, higher glutamate/GABA ratio and dopamine. Conversely, high succinate correlated with higher MMSE score. Serial analysis demonstrated a reproducible, time-dependent, reciprocal correlation between changes in lactate and GABA concentrations. While high lactate and low GABA correlated with tumor contrast enhancing volume, they correlated more significantly with lower MMSE scores than tumor volumes. CONCLUSIONS We provide evidence that lactate production and Warburg metabolism may impact neurotransmitter dysregulation and neurocognition in CNS lymphomas. We identify novel metabolomic biomarkers that may be applied in future studies of neurocognition in CNS lymphomas. Elucidation of mechanistic interactions between lymphoma metabolism, neurotransmitter imbalance and neurocognition may promote interventions that preserve cognitive function.
Stage I–II diffuse large B-cell lymphoma treated with rituximab and chemotherapy with or without radiotherapy

Abstract We set to identify prognostic factors in a retrospective cohort of consecutive patients with stage I-II diffuse large B-cell lymphoma treated with rituximab-chemotherapy with or without radiotherapy from 2001 through 2017 at our institution. We identified 143 patients with median follow-up of 7.7 years. The majority were male (59.4%), had stage II (53.1%), had stage-modified IPI 0–1 (smIPI, 58.1%), and had non-bulky disease (<7 cm, 68.5%). 99 patients (69.2%) received rituximab-chemotherapy followed by radiotherapy, and 44 patients (30.8%) received rituximab-chemotherapy alone. The 5-year progression-free survival (PFS) and overall survival (OS) were 81.2% and 88.9%, respectively. The 5-year PFS for those with smIPI 0–1 versus 2–4 was 89.5% versus 69.7%, respectively (P = 0.005). Bulky disease (≥7 cm) was associated with worse PFS and OS on univariable and multivariable analyses (P < 0.05). Patients with smIPI 0–1 without bulky disease have excellent outcomes. However, patients with smIPI 2–4 or bulky disease have a high risk of progression.
[Long non-coding RNA UPK1A-AS1 promotes glycolysis in hepatocellular carcinoma cells via stabilization of HIF-1α].

OBJECTIVE To investigate the effect of long non-coding RNA UPK1A-AS1 on glycolysis of hepatocellular carcinoma cells and its underlying molecular mechanisms. OBJECTIVE A hepatocellular carcinoma (HCC) cell line with lentivirus-mediated stable UPK1A-AS1 overexpression and the cells infected with a negative control lentiviral vector were cultured under normoxic (21% O2) or hypoxic (1% O2) conditions for 24 h. The effect of UPK1A-AS1 overexpression on glycolysis of the HCC cells was examined. The expressions of glycolysis-related genes HIF1A, GLUT1, HK1, HK2 and PGK1 were detected by qRTPCR, and the effect of UPK1A-AS1 overexpression on HRE activity was detected by dual luciferase report assay. The HCC cells were treated with cycloheximide to detect the effect of UPK1A-AS1 overexpression on the stability of HIF-1α protein. Immunoprecipitation assay was used to analyze the changes in ubiquitin modification of HIF-1α protein in response to UPK1A-AS1 overexpression. The effects of UPK1A-AS1 overexpression and RNA interference of HIF-1α expression on glucose consumption, lactate production and expressions of HRE activity and glycolysis-related genes (HK1, HK2 and PGK1) were examined in the HCC cells. OBJECTIVE Compared with the control group, overexpression of UPK1A-AS1 significantly promoted glucose consumption and lactate production in HCC cells under both normoxic and hypoxic conditions (P < 0.05). Overexpression of UPK1A-AS1 significantly increased the expression of glycolysis-related genes including HIF1A, GLUT1, HK1, HK2 and PGK1. Upregulation of UPK1A-AS1 obviously promoted the transcriptional activity of HRE (P < 0.05). Western blotting showed that UPK1A-AS1 overexpression obviously increased the stability of HIF-1α protein and significantly reduced ubiquitin modification of HIF-1α. Downregulation of HIF-1α obviously reversed the effect of UPK1A-AS1 overexpression in promoting glucose consumption, lactate production and HRE luciferase activity. Silencing HIF-1α also suppressed the upregulation of glycolysis-related gene expressions induced by UPK1A-AS1 overexpression (P < 0.05). OBJECTIVE The long noncoding RNA UPK1A-AS1 upregulates the expression of glycolysis-related genes by stabilizing the expression of HIF-1α, thereby promoting glycolysis level in HCC cells.
Contributions of mass spectrometry in the Australian Wine Research Institute to advances in knowledge of grape and wine constituents

Since 1971 mass spectrometry (MS) has made a significant contribution to wine research at the Australian Wine Research Institute (AWRI). In the past decade (1995‐2004), MS has been involved in an expanded range of studies and now accounts for approximately 40% of AWRI publications appearing in peerreviewed scientific journals. Studies involving MS include the analysis of grape-derived and fermentationderived volatiles, oak volatiles, taint compounds, proteins, pigments and tannins. We discuss the contribution MS has made to wine research at the AWRI and the significant advances made by key scientists in this area. In particular, this review focuses on three main areas of analysis of compounds important to wine quality ‐ volatile aroma and off-flavour compounds, involatile larger molecules such as proteins and tannins, and investigations into taint problems. Abbreviations 4-EP 4-ethylphenol; APCI atmospheric pressure chemical ionisation; CI chemical ionisation; ECD electron capture detector; EI electron impact ionisation; ESI electrospray ionisation; ESI-MS electrospray ionisation mass spectrometry; FID flame ionisation detector; GC gas chromatography; GC-MS gas chromatography-mass spectrometry; GC-sniff GC-olfactory detection; HPLC high performance liquid chromatography; LC-MS high performance liquid chromatography-electrospray ionisation-mass spectrometry; LC liquid chromatography; MALDI matrix assisted laser desorption ionisation; MLCCC multi layer coil countercurrent chromatography; MS mass spectrometry; MSD mass selective detector; MS/MS tandem mass spectrometry; PDA photo-diode array detector; PDMS polydimethylsiloxane; PR pathogenesis related; SBSE stir bar sorptive extraction; SIDA stable isotope dilution analysis; SPME solid-phase microextraction; TCA 2,4,6-trichloroanisole; TDN 1,1,6-trimethyl-1,2-dihydronaphthalene; TPB (E)-1-(2,3,6-trimethylphenyl) buta-1,3-diene; Trap-MS protein trap-mass spectrometry
The Computer Will See You Now: Overcoming Barriers to Adoption of Computer-Assisted History Taking (CAHT) in Primary Care

Patient health information is increasingly collected through multiple modalities, including electronic health records, wearables, and connected devices. Computer-assisted history taking could provide an additional channel to collect highly relevant, comprehensive, and accurate patient information while reducing the burden on clinicians and face-to-face consultation time. Considering restrictions to consultation time and the associated negative health outcomes, patient-provided health data outside of consultation can prove invaluable in health care delivery. Over the years, research has highlighted the numerous benefits of computer-assisted history taking; however, the limitations have proved an obstacle to adoption. In this viewpoint, we review these limitations under 4 main categories (accessibility, affordability, accuracy, and acceptability) and discuss how advances in technology, computing power, and ubiquity of personal devices offer solutions to overcoming these.
Conserved dual-mode gene regulation programs in higher eukaryotes

Abstract Recent genomic data analyses have revealed important underlying logics in eukaryotic gene regulation, such as CpG islands (CGIs)-dependent dual-mode gene regulation. In mammals, genes lacking CGIs at their promoters are generally regulated by interconversion between euchromatin and heterochromatin, while genes associated with CGIs constitutively remain as euchromatin. Whether a similar mode of gene regulation exists in non-mammalian species has been unknown. Here, through comparative epigenomic analyses, we demonstrate that the dual-mode gene regulation program is common in various eukaryotes, even in the species lacking CGIs. In cases of vertebrates or plants, we find that genes associated with high methylation level promoters are inactivated by forming heterochromatin and expressed in a context-dependent manner. In contrast, the genes with low methylation level promoters are broadly expressed and remain as euchromatin even when repressed by Polycomb proteins. Furthermore, we show that invertebrate animals lacking DNA methylation, such as fruit flies and nematodes, also have divergence in gene types: some genes are regulated by Polycomb proteins, while others are regulated by heterochromatin formation. Altogether, our study establishes gene type divergence and the resulting dual-mode gene regulation as fundamental features shared in a broad range of higher eukaryotic species.