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SUMMARY: The Local Disordered Region Sampling (LDRS, pronounced loaders) tool is a new module developed for IDPConformerGenerator, a previously validated approach to model intrinsically disordered proteins (IDPs). The IDPConformerGenerator LDRS module provides a method for generating all-atom conformations of intrinsically disordered protein regions at N- and C-termini of and in loops or linkers between folded regions of an existing protein structure. These disordered elements often lead to missing coordinates in experimental structures or low confidence in predicted structures. Requiring only a pre-existing PDB or mmCIF formatted structural template of the protein with missing coordinates or with predicted confidence scores and its full-length primary sequence, LDRS will automatically generate physically meaningful conformational ensembles of the missing flexible regions to complete the full-length protein. The capabilities of the LDRS tool of IDPConformerGenerator include modeling phosphorylation sites using enhanced Monte Carlo-Side Chain Entropy, transmembrane proteins within an all-atom bilayer, and multi-chain complexes. The modeling capacity of LDRS capitalizes on the modularity, the ability to be used as a library and via command-line, and the computational speed of the IDPConformerGenerator platform. AVAILABILITY AND IMPLEMENTATION: The LDRS module is part of the IDPConformerGenerator modeling suite, which can be downloaded from GitHub at https://github.com/julie-forman-kay-lab/IDPConformerGenerator. IDPConformerGenerator is written in Python3 and works on Linux, Microsoft Windows, and Mac OS versions that support DSSP. Users can utilize LDRSs Python API for scripting the same way they can use any part of IDPConformerGenerators API, by importing functions from the idpconfgen.ldrs_helper library. Otherwise, LDRS can be used as a command line interface application within IDPConformerGenerator. Full documentation is available within the command-line interface as well as on IDPConformerGenerators official documentation pages (https://idpconformergenerator.readthedocs.io/en/latest/).

This work investigates the conditions for net flow generation by a straight tube with a cross-sectional area harmonically varying in time that connects two tanks—a problem that is mainly found in the design of impedance pumps. By assuming a quasi-one-dimensional flow and applying continuity and momentum equations, a first-order differential equation with respect to the flow rate is derived and presented for the first time, including a nonlinear term that is responsible for net flow rate generation. Namely, the net flow rate is found to be nonzero (as is the nonlinear term) if the cross-sectional areas of the two tanks are unequal and one of them is smaller than that of the straight tube. In this case, the flow is directed from the smaller to the larger tank and the net flow rate increases with the frequency of the tube’s cross-sectional area variation. In contrast, when the tanks’ cross-sections are equal, the net flow is generated only if a valve is installed, e.g., at one end of the tube, due to the large asymmetries imposed in the hydraulic losses with respect to the tube mid-length. Compared with constant valve opening, the net flow rate is augmented significantly if the valve opening is time-dependent. By employing the same equation, the flow rate of an intra-aortic counter-pulsating balloon pump is also examined, in which the valve (representing the aortic valve) opens during the shrinkage of the tube, and it is shown that the net flow rate increases with the frequency and amplitude of the tube’s cross-sectional area. Conclusively, the harmonic oscillation in time of a tube’s wall can cause unidirectional flow only if asymmetric losses are present with respect to its mid-length.

Colostrum is essential for the survival and development of newborn mammals. This primary source of nourishment during the first days of infant life is rich in functional components conductive to the enhancement of neonate immunity and growth. Compared with mature milk, a higher protein and peptide content is observed in colostrum, whilst it is low in fat and carbohydrates. The functional properties of colostrum are closely linked to the release of bioactive peptides during the gastrointestinal digestion of colostrum proteins. Our study aimed to comprehensively analyze the whey proteome of colostrum from indigenous Greek goats and to examine the influence of bioactive peptides released during digestion on human metabolism. Colostrum and mature milk samples from healthy ewes were subjected to nanoLC-MS/MS analysis, revealing differentially expressed proteins. These proteins were functionally characterized and subjected to in silico digestion. Using machine learning models, we classified the peptide functional groups, while molecular docking assessed the binding affinity of the proposed angiotensin-converting enzyme (ACE)- and dipeptidyl peptidase IV (DPPIV)-inhibitory peptides to their target molecules. A total of 898 proteins were identified in colostrum, 40 of which were overexpressed compared with mature milk. The enzymatic cleavage of upregulated proteins by key gastrointestinal tract proteases and the downstream analysis of peptide sequences identified 117 peptides predicted (with >80% confidence) to impact metabolism, primarily through modulation of the renin–angiotensin system, insulin secretion, and redox pathways. This work advances our understanding of dietary bioactive peptides and their relevance to human metabolism, highlighting the potential health benefits of colostrum consumption.

Per- and polyfluoroalkyl substances (PFASs) are contaminants of great concern due to their ubiquitous environmental occurrence in the environment and their potential adverse effects on organisms. There is currently limited information regarding the occurrence of PFASs in Scopoli’s Shearwater (Calonectris diomedea). In this study, two feather samples per bird were obtained from 26 adults on Strofades colony (Ionian Sea/Greece) during the early phase of the chick-rearing period (late July 2019). The samples consisted of barbs and barbules of the primary feathers, P1 and P10, reflecting pollution pressures at the time and the place of feather growth, i.e., at the species’ breeding and wintering grounds for P1 and P10, respectively. There were 25 PFAS detected in the feathers, with detection rates ranging from 2% (perfluorododecanoic acid—PFDoDA; perfluorohexane sulfonate—PFHxS; 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate—9Cl-PF3ONS; 2,3,3,3-tetrafluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)propanoate—Gen-X) to 98% (sodium 1H,1H,2H,2H-perfluorooctane sulfonate; 6:2 FTSA). ∑PFAS ranged from 25.93 ng/g to 426.86 ng/g of feather sample. The highest mean concentration (109.10 ng/g feather) was reported for perfluorononanoic acid (PFNA). No significant differences in PFAS concentrations with high detection rate (>20%) were found according to the sex of the birds. PFAS concentrations with a detection rate > 20% in the P1 vs. P10 feathers of Scopoli’s Shearwater adults were not significantly different, reflecting the fact that breeding grounds in the Mediterranean and wintering grounds in the Atlantic seem to be contaminated with similar PFASs levels, even though some compounds showed regional trends.

Abstract Background Headaches are the most common complaints among pediatric populations. Determining the cause and appropriate treatment for headaches may be challenging and costly, and the impact of headaches on the lives of patients and their families is not well understood. Objective A systematic literature review was conducted to examine what PROMs are currently used, and to identify quality of life (QoL) concepts important to children suffering from headaches and any known determinants of QoL. Methods Embase, Medline, Web of Science, CINAHL, EBSCOhost, PsychINFO, Cochrane CENTRAL and Google Scholar were searched from their inception through to June 2021. Studies investigating QoL, using a validated outcome measure in pediatric patients with headaches, were included. Relevant studies were identified through title and abstract screening and full text review by two independent reviewers. A citation review of included studies was performed. QoL concepts were extracted from the outcome measures that were used in each study to develop a preliminary conceptual model of QoL in children suffering from headaches. Determinants of QoL were also identified and categorized. Results A total of 5421 studies were identified in the search. Title and abstract screening resulted in the exclusion of 5006 studies. Among the 415 studies included for full text review, 56 were eligible for final analysis. A citation review resulted in the addition of five studies. Most studies were conducted in high-income countries and included a patient-sample accordingly (n = 45 studies). Sixteen different PROMs were identified in the included studies, of which the PedsQL was used the most often (n = 38 studies). The most common health concepts reported were physical functioning (n = 113 items), social and psychological wellbeing (N = 117, n = 91 resp.). Twenty-five unique determinants of QoL were extracted from the included studies. Conclusion There is a need for a condition-specific PROM to facilitate the measurement of QoL outcomes in the pediatric headache population. A conceptual model was developed based on the findings from the health concepts. Findings from this review could be used for future qualitative interviews with pediatric patients with headaches to elicit and refine important QoL concepts.

Background:. The Satisfaction with Face Overall and Psychological Function scales are the most frequently used FACE-Q Aesthetics module scales. This study aimed to extend their range of measurement by adding and testing new concepts. We aimed to create FACE-Q Aesthetics item libraries. Methods:. In-depth concept elicitation interviews were conducted. Concepts were formed into items and refined through multiple rounds of patient and expert input. The items were tested with people living in the United States, Canada, and the United Kingdom who had minimally invasive facial aesthetic treatments. Participants were recruited through an online platform (ie, Prolific). Psychometric properties were examined using Rasch measurement theory analysis, test–retest reliability, and construct validity. Results:. We conducted 26 interviews. New concepts were developed into items and refined with input from 12 experts, 11 clinic patients, and 184 Prolific participants. A sample of 1369 Prolific participants completed 52 appearance and 22 psychological items. After removing 10 and 2 items respectively, the psychometric tests provided evidence of reliability with the person separation index, Cronbach alpha, and test–retest reliability values without extremes of 0.88 or more. For validity, lower scores were associated with looking older than one’s age, being more bothered by facial skin laxity, treatment wearing off, and having deeper lines on Merz Assessment scales. Short-form scales formed from the 42 appearance items provide examples of item library application. Conclusions:. This study provides an innovative means to customize scales to measure appearance and psychological function that maximizes content validity and minimizes respondent burden in the context of minimally invasive treatments.

The increased prevalence of obesity worldwide has been implicated in the alarming rise of the incidence of gestational diabetes and preeclampsia, which are both considered threatening conditions for both mother and fetus. We studied gene polymorphisms of the proinflammatory cytokine Interleukin 6 (IL-6) and the gene expression levels of VEGF (vascular endothelial growth factor) and VEGF-R (endothelial growth factor receptor), all known to be involved in pregnancy complications, aiming to identify possible predisposing risk factors in pregnancies with obesity. The G allele of IL-6 was found to correspond with an increased risk for gestational diabetes and preeclampsia occurrence. Furthermore, in obese pregnant mothers with either gestational diabetes or pre-existing type 2 diabetes and those who developed preeclampsia, it was confirmed that gene expression levels of VEGF were reduced while they were increased for VEGF receptors. We conclude that the genetic profile of an obese pregnant woman shares a common background with that of a patient with pre-existing type 2 diabetes mellitus, and therefore predisposes them to complications in pregnancy.

Alpha-synuclein (SNCA) accumulation plays a central role in the pathogenesis of Parkinson's disease. Determining and interfering with the mechanisms that control SNCA expression is one approach to limiting disease progression. Currently, most of our understanding of SNCA regulation is protein-based. Post-transcriptional mechanisms directly regulating SNCA mRNA expression via its 3′ untranslated region (3′UTR) were investigated here. Mass spectrometry of proteins pulled down from murine brain lysates using a biotinylated SNCA 3′UTR revealed multiple RNA-binding proteins, of which HNRNPD/AUF1 was chosen for further analysis. AUF1 bound both proximal and distal regions of the SNCA 3′UTR, but not the 5′UTR or CDS. In the nucleus, AUF1 attenuated SNCA pre-mRNA maturation and was indispensable for the export of SNCA transcripts. AUF1 destabilized SNCA transcripts in the cytosol, primarily those with shorter 3′UTRs, independently of microRNAs by recruiting the CNOT1-CNOT7 deadenylase complex to trim the polyA tail. Furthermore, AUF1 inhibited SNCA mRNA binding to ribosomes. These data identify AUF1 as a multi-tasking protein regulating maturation, nucleocytoplasmic shuttling, stability and translation of SNCA transcripts.

The objective of this study was the presentation of quantitative characteristics regarding the scientific content and bibliometric details of the relevant publications. In total, 156 papers were considered. Most papers presented original studies (n = 135), and fewer were reviews (n = 21). Most original articles (n = 101) referred to work involving cattle. Most original articles described work related to the diagnosis (n = 72) or pathogenesis (n = 62) of mastitis. Most original articles included field work (n = 75), whilst fewer included experimental (n = 31) or laboratory (n = 30) work. The tissue assessed most frequently in the studies was milk (n = 59). Milk was assessed more frequently in studies on the diagnosis (61.1% of relevant studies) or pathogenesis (30.6%) of the infection, but mammary tissue was assessed more frequently in studies on the treatment (31.0%). In total, 47 pathogens were included in the studies described; most were Gram-positive bacteria (n = 34). The three bacteria most frequently included in the studies were Staphylococcus aureus (n = 55 articles), Escherichia coli (n = 31) and Streptococcus uberis (n = 19). The proteomics technology employed more often in the respective studies was liquid chromatography-tandem mass spectrometry (LC-MS/MS), either on its own (n = 56) or in combination with other technologies (n = 40). The median year of publication of articles involving bioinformatics or LC-MS/MS and bioinformatics was the most recent: 2022. The 156 papers were published in 78 different journals, most frequently in the Journal of Proteomics (n = 16 papers) and the Journal of Dairy Science (n = 12). The median number of cited references in the papers was 48. In the papers, there were 1143 co-authors (mean: 7.3 ± 0.3 co-authors per paper, median: 7, min.–max.: 1–19) and 742 individual authors. Among them, 15 authors had published at least seven papers (max.: 10). Further, there were 218 individual authors who were the first or last authors in the papers. Most papers were submitted for open access (n = 79). The median number of citations received by the 156 papers was 12 (min.–max.: 0–339), and the median yearly number of citations was 2.0 (min.–max.: 0.0–29.5). The h-index of the papers was 33, and the m-index was 2. The increased number of cited references in papers and international collaboration in the respective study were the variables associated with most citations to published papers. This is the first ever scientometrics evaluation of proteomics studies, the results of which highlighted the characteristics of published papers on mastitis and proteomics. The use of proteomics in mastitis research has focused on the elucidation of pathogenesis and diagnosis of the infection; LC-MS/MS has been established as the most frequently used proteomics technology, although the use of bioinformatics has also emerged recently as a useful tool.

Peristaltic flow in a straight rectangular duct is examined imposed by contraction pulses implemented by pairs of horizontal cylindrical segments with their axes perpendicular to the flow direction. The wave propagation speed is considered in such a range that triggers a laminar fluid motion. The setting is analyzed over a set of variables which includes the propagation speed, the relative occlusion, the modality of the squeezing pulse profile and the Carreau power index. The numerical solution of the equations of motion on Cartesian meshes is grounded in the immersed boundary method. An increase in the peristaltic pulse modality leads to the reduction in the shear rate levels on the central tube axis and to the movement of the peristaltic characteristics to higher pressure values. The effect of the no slip side walls (NSSWs) is elucidated by the collation with relevant results for the flow field produced under the same assumptions though with slip side walls (SSWs). Shear thinning behavior exhibits a significantly larger effect on transport efficiency for the NSSWs duct than on the SSWs duct.

Abstract Purpose The impact of the COVID-19 pandemic on psychological well-being will likely be long-lasting. Efforts directed towards monitoring the onset and progression of distress and mental health disorders are needed to identify and prioritize at-risk populations. This study assesses the psychological well-being of the United States (US) general population during the early phase of the COVID-19 COVID-19 pandemic using validated patient-reported outcome measures (PROMs). Methods A cross-sectional study design was used. Adults (18 years or older) who could read and write in English were recruited through Prolific in May 2020. Participants completed a REDCap survey including demographic and health-related questions and three PROMs measuring global health (PROMIS-10 Global Health), anxiety [Generalized Anxiety Disorder Scale-7 (GAD-7)], and depression [Patient Health Questionnaire-9 (PHQ-9)]. A multivariable linear regression was used to identify key factors associated with worse psychological well-being. Results Mean age of the 2023 participants was 31.92 ± 11.57 years (range, 18–82). Participants were mainly White (64.7%, n = 1309), female (52.2%, n = 1057), working full-time before the pandemic (43.5%, n = 879), and completed a college, trade, or university degree (40.7%, n = 823). Most participants reported mild to severe anxiety (57.3%, n = 1158) and depression (60%, n = 1276) on the GAD-7 and PHQ-9, respectively. Patient characteristics associated with worse psychological well-being included: age ≤ 39 years, non-White, female or gender diverse, BMI ≥ 30, uninsured, annual income ≤ $49,999 (USD), lower educational attainment, and belief that COVID-19 is deadlier than flu. Conclusion PROMs can be used to assess and monitor psychological well-being during the COVID-19 pandemic and to inform the planning and delivery of targeted public health interventions to support at-risk populations.

Abstract Background Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. Methods We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. Results Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) − 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35–3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06–0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. Conclusions Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55.

The study presents a generalized analytical solution of the laminar, oscillatory, creeping flow of an incompressible Newtonian fluid in a porous circular pipe with spatiotemporally periodic suction/injection at the wall. The analytical solution is examined for a variety of values of the dimensionless parameters, namely the Womersley number and the dimensionless suction/injection number.