Miracle-dz/UniFAR-FTUs huggingface dataset:
Nanoscale Restructuring of Polymer Materials to Produce Single Polymer Composites and Miscible Blends

I summarize work conducted in our laboratories over the past 30 years using small host molecules to restructure polymer materials at the nanometer level. Certain small molecules, such as the cyclic starches cyclodextrins (CDs) and urea (U) can form non-covalent crystalline inclusion compounds (ICs) with a range of guest molecules, including many polymers. In polymer-CD- and -U-ICs, guest polymer chains reside in narrow channels created by the host molecule crystals, where they are separated and highly extended. When the host crystalline lattice is carefully removed, the guest polymer chains coalesce into a bulk sample with an organization that is distinct from that normally produced from its melt or from solution. Amorphous regions of such coalesced polymer samples have a greater density, likely with less chain entanglement and more chain alignment. As a consequence, after cooling from their melts, coalesced amorphous polymers show glass-transition temperatures (Tgs) that are elevated above those of samples prepared from their solutions or melts. Upon cooling from their melts, coalesced samples of crystallizable polymers show dramatically-increased abilities to crystallize more rapidly and much closer to their melting temperatures (Tms). These unique behaviors of polymers coalesced from their CD- and U-ICs are unexpectedly resistant to extended annealing above their Tgs and Tms. Taking advantage of this behavior permits us to create polymer materials with unique and improved properties. Among these are amorphous polymers with elevated Tgs and semi-crystalline polymers with finer more uniform morphologies. Improved mechanical properties can be achieved through self-nucleation with small amounts of the same polymer made rapidly crystallizable through coalescence from its CD- or U-IC. This can lead to single polymer composites with as-received polymer matrices and self-nucleated reinforcements. Through simultaneous formation and subsequent coalescence from their common CD–ICs, stable well-mixed blends can be achieved between any two or more polymers, despite their inherent immiscibilities. Such coalesced and well-mixed blends are also resistant to phase segregation when heated for extensive periods well above their Tgs and Tms.
Work-Related Intervention Needs and Potential Occupational Outcomes among Medical Assistants: A Cross-Sectional Study

Medical assistants’ (MAs) working conditions have been characterized as precarious, and workplace-related intervention needs have been identified. However, strategies to change the MAs adverse working conditions are mostly seen on an individual level, including leaving the employer or even the profession. Since such intentions are antecedents of actual turnover, we aimed to quantify the potential link of reported unmet intervention needs with unfavorable occupational outcomes. Data were collected by means of a nationwide survey among medical assistants (n = 994) in Germany (September 2016–April 2017). The three subscales working conditions, reward from the supervisor, and task-related independence were derived from a 12-item instrument regarding work-related interventions needs (the independent variables). We used subscale-specific z-scores and a total needs z-score. The four outcome variables (i.e., intention to leave the employer, intention to leave the MA profession, choosing MA profession again, and recommending MA profession to young people) were dichotomized, and logistic regression analyses were performed and limited to MAs in employment (n = 887). We found that increasing needs according to the categorized total needs score were associated with increasing odds of all occupational outcomes. Needs pertaining to working conditions and reward from the supervisor were the strongest determinants of MAs’ consideration of leaving their employer or profession (Odds ratios: 1.55–2.61). In summary, our study identified unmet work-related intervention needs that are associated with unfavorable occupational outcomes. In light of staffing shortage in health care, the identified needs should be addressed to ensure that sufficient recruitment of junior staff in the profession of medical assistants remains feasible and that experienced staff is retained.
Characterisation of extracellular redox enzyme concentrations in response to exercise in humans.

Redox enzymes are ubiquitous proteins that modulate intracellular redox balance and can be secreted in response to cellular oxidative stress, potentially modulating systemic inflammation. Both aerobic and resistance exercise are known to cause acute systemic oxidative stress and inflammation; however, how redox enzyme concentrations alter in extracellular fluids following bouts of either type of exercise is unknown. Recreationally active males (n=26, age 28 ± 8 years) took part in either: 1) two separate energy-matched cycling bouts: one of moderate intensity (MOD) and a bout of high intensity interval exercise (HIIE) or 2) a resistance exercise protocol. Alterations in plasma (study 1) and serum (study 2) peroxiredoxin (PRDX)-2, PRDX-4, superoxide dismutase-3 (SOD3), thioredoxin (TRX-1), TRX-reductase and Interleukin (IL)-6 were assessed before and at various timepoints after exercise. There was a significant increase in SOD3 (+1.5 ng/mL) and PRDX-4 (+5.9 ng/mL) concentration following HIIE only, peaking at 30- and 60-min post-exercise respectively. TRX-R decreased immediately and 60-min following HIIE (-7.3 ng/mL) and MOD (-8.6 ng/mL) respectively. In non-resistance trained males, no significant changes in redox enzyme concentrations were observed up to 48 hours following resistance exercise, despite significant muscle damage. IL-6 concentration increased in response to all trials, however there was no significant relationship between absolute or exercise-induced changes in redox enzyme concentrations. These results collectively suggest that HIIE, but not MOD or eccentric exercise increase the extracellular concentration of PRDX-4 and SOD3. Exercise-induced changes in redox enzyme concentration do not appear to directly relate to systemic changes in IL-6 concentration.
Individual-level antibody dynamics reveal potential drivers of influenza A seasonality in wild pig populations.

Swine are important in the ecology of influenza A viruses (IAV) globally. Understanding the ecological role of wild pigs in IAV ecology has been limited because surveillance in wild pigs is often for antibodies (serosurveillance) rather than IAVs, as in humans and domestic swine. As IAV antibodies can persist long after an infection, serosurveillance data are not necessarily indicative of current infection risk. However, antibody responses to IAV infections cause a predictable antibody response, thus time of infection can be inferred from antibody levels in serological samples, enabling identification of risk factors of infection at estimated times of infection. Recent work demonstrates that these quantitative antibody methods (QAM) can accurately recover infection dates, even when individual-level variation in antibody curves is moderately high. Also, the methodology can be implemented in a survival analysis (SA) framework to reduce bias from opportunistic sampling. Here we integrated QAM and SA and applied this novel QAM-SA framework to understand the dynamics of IAV infection risk in wild pigs seasonally and spatially, and identify risk factors. We used national-scale IAV serosurveillance data from 15 U.S. states. We found that infection risk was highest Jan.-Mar. (54% of 61 estimated peaks), with 24% of estimated peaks occurring from May-Jul., and some low-level of infection risk occurring year-round. Time-varying IAV infection risk in wild pigs was positively correlated with humidity and IAV infection trends in domestic swine and humans, and did not show wave-like spatial spread of infection among states, nor more similar levels of infection risk among states with more similar meteorological conditions. Effects of host sex on IAV infection risk in wild pigs were generally not significant. Because most of the variation in infection risk was explained by state-level factors or infection risk at long-distances, our results suggested that predicting IAV infection risk in wild pigs is complicated by local ecological factors and potentially long-distance translocation of infection. In addition to revealing factors of IAV infection risk in wild pigs, our framework is broadly applicable for quantifying risk factors of disease transmission using opportunistic serosurveillance sampling, a common methodology in wildlife disease surveillance. Future research on the factors that determine individual-level antibody kinetics will facilitate the design of serosurveillance systems that can extract more accurate estimates of time-varying disease risk from quantitative antibody data.
Haemotherapy with Fibrinogen for Perioperative Bleeding Prevention—A View on Arterial Thrombogenesis and Myocardial Infarction in the Rat In Vivo

Major blood loss during cardiac surgery is associated with increased morbidity and mortality. Clinical pilot studies indicated that preoperative fibrinogen supplementation reduces postoperative blood loss without increasing thrombotic complications. However, an increase in fibrinogen concentration might rather aggravate pre-existing thrombosis than increase the incidence of thrombotic events. Therefore, we investigated, in the present study, whether fibrinogen supplementation influences (1) arterial thrombus formation, (2) the extent of myocardial infarction and (3) the cardioprotective effect of ischaemic preconditioning. Arterial thrombogenesis of the femoral artery was induced by topic FeCl3 treatment in anaesthetised Wistar rats after pretreatment with 60 mg/kg (Fiblow), 120 mg/kg (Fibhigh) or vehicle (Con). Vessel blood flow was monitored, and time to vessel occlusion was analysed as a marker for arterial thrombogenesis. In addition, regional myocardial I/R injury was induced by temporary left coronary artery occlusion in rats pretreated with or without fibrinogen supplementation. In additional groups, ischaemic preconditioning (IPC) was induced by 3 cycles of 5 min of ischaemia/reperfusion. In all groups, myocardial infarct size was determined by triphenyltetrazoliumchlorid staining. Arterial thrombogenesis was not affected by fibrinogen pretreatment. No differences in time until vessel occlusion between Con, Fiblow and Fibhigh groups were observed. In addition, fibrinogen supplementation in low and high concentrations had no effect on infarct size after regional myocardial ischaemia and reperfusion (Fiblow: 66 ± 10%, Fibhigh: 62 ± 9%; each ns vs. Con). IPC reduced infarct size from 62 ± 14% to 34 ± 12% (p < 0.05 vs. Con). Furthermore, both fibrinogen concentrations did not affect cardioprotection by ischaemic preconditioning (Fiblow + IPC: 34 ± 11%, Fibhigh + IPC: 31 ± 13%; each ns vs. IPC). Haemotherapy with fibrinogen did not affect arterial thrombogenesis, myocardial infarction and the cardioprotective effect of ischaemic preconditioning.
Role of rapid diagnostics for viral respiratory infections in antibiotic prescribing decision in the emergency department

Abstract Objective: To describe the frequency of antibiotic prescriptions in patients with known viral respiratory infections (VRIs) diagnosed by polymerase chain reaction (PCR) in 3 emergency departments (EDs) and to identify patient characteristics that influence the prescribing of antibiotics by ED physicians despite PCR confirmation of viral cause. Design: Retrospective, observational analysis of patients with PCR-diagnosed VRI discharged from 3 acute-care hospital EDs within 1 health system. Results: In total, 323 patients were discharged from the ED with a VRI diagnosis, of whom 68 were prescribed antibiotics (21.1%). These patients were older (median, 59.5 vs 43 years; P = .04), experienced symptoms longer (median, 4 vs 2 days; P = .002), were more likely to have received antibiotics in the preceding 7 days (27.9% vs 9.8%; P < .001), and had higher proportions of abnormal chest X-rays (64.5% vs 28.4%; P < .001). Patients were more likely to receive antibiotics for a diagnosis of pneumonia (39.7% vs 1.6%; P < .001) or otitis media (7.4% vs 0.4%; P = .002), and were less likely with diagnosis of upper respiratory infection (2.9% vs 13.7%; P = .02) or influenza (20.6% vs 44.3%; P < .001). Conclusions: Despite a diagnosis of VRI, one-fifth of ED patients were prescribed antibiotics. Patient characteristics including age, duration of symptoms, abnormal chest X-rays, and specific diagnosis may increase provider concern for concurrent bacterial infections. Opportunities exist for antimicrobial stewardship strategies to incorporate rapid diagnostics in promoting judicious antibiotic usage in the ED.
Negative CD19 expression is associated with inferior relapse‐free survival in children with RUNX1‐RUNX1T1–positive acute myeloid leukaemia: results from the Japanese Paediatric Leukaemia/Lymphoma Study Group AML‐05 study

We performed a retrospective analysis of leukaemic surface antigen expression and genomic data from a total of 100 RUNX1‐RUNX1T1–positive paediatric acute myeloid leukaemia (AML) patients enrolled in the Japanese Paediatric Leukaemia/Lymphoma Study Group (JPLSG) AML‐05 protocol to determine risk factors for relapse. In univariate analysis, the KIT exon 17 mutation (n = 21) and CD19 negativity (n = 59) were significant risk factors for relapse (P = 0·01). In multivariate analysis, CD19 negativity was the sole significant risk factor for relapse (hazard ratio, 3·09; 95% confidence interval, 1·26–7·59; P < 0·01), suggesting that biological differences between CD19‐positive and CD19‐negative RUNX1‐RUNX1T1 AML patients should be investigated.
Cytokine and Sclerostin Response to High-Intensity Interval Running versus Cycling.

PURPOSE This study examined whether the exercise-induced changes in inflammatory cytokines differ between impact and no-impact high intensity interval exercise, and whether they are associated with post-exercise changes in sclerostin. METHODS Thirty-eight females (n=19, 22.6±2.7 years) and males (n=19, 22.3±2.4 years) performed two high-intensity interval exercise trials in random order (cross-over design): running on a treadmill and cycling on a cycle ergometer. Trials consisted of eight repetitions of 1 min running or cycling at ≥90% maximal heart rate, separated by 1 min passive recovery intervals. Blood was collected pre-exercise, and 5 min, 1h, 24h and 48h post-exercise, and was analyzed for serum levels of interleukins (IL-1β, IL-6, IL-10), tumor necrosis factor alpha (TNF-α) and sclerostin. RESULTS Inflammatory cytokines significantly increased over time in both sexes with some differences between trials. Specifically, IL-1β significantly increased from pre- to 5 min after both trials (23%, p<0.05), IL-6 increased 1h following both trials (39%, p<0.05), IL-10 was elevated 5 min after running (20%, p<0.05) and 1h after both running and cycling (41% and 64%, respectively, p<0.05), and TNF-α increased 5 min after running (10%, p<0.05). Sclerostin increased 5 min following both trials, with a greater increase in males than in females (62 vs 32 pg/ml in running, p=0.018; 63 vs 30 pg/ml in cycling, p=0.004). In addition, sclerostin was significantly correlated with the corresponding changes in inflammatory cytokines and 34% of the variance in its post-exercise gain score (Δ) was explained by sex and the corresponding gain scores in TNF-α, which was the strongest predictor. CONCLUSION A single bout of either impact or no-impact high-intensity exercise induces changes in inflammatory cytokines, which are associated with the post-exercise increase in sclerostin.
Application of qualitative and quantitative uncertainty assessment tools in developing ranges of plausible toxicity values for 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin

Increasing interest in characterizing risk assessment uncertainty is highlighted by recent recommendations from the National Academy of Sciences. In this paper we demonstrate the utility of applying qualitative and quantitative methods for assessing uncertainty to enhance risk‐based decision‐making for 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin. The approach involved deconstructing the reference dose (RfD) via evaluation of the different assumptions, options, models and methods associated with derivation of the value, culminating in the development of a plausible range of potential values based on such areas of uncertainty. The results demonstrate that overall RfD uncertainty was high based on limitations in the process for selection (e.g., compliance with inclusion criteria related to internal validity of the co‐critical studies, consistency with other studies), external validity (e.g., generalizing findings of acute, high‐dose exposure scenarios to the general population), and selection and classification of the point of departure using data from the individual studies (e.g., lack of statistical and clinical significance). Building on sensitivity analyses conducted by the US Environmental Protection Agency in 2012, the resulting estimates of RfD values that account for the uncertainties ranged from ~1.5 to 179 pg/kg/day. It is anticipated that the range of RfDs presented herein, along with the characterization of uncertainties, will improve risk assessments of dioxins and provide important information to risk managers, because reliance on a single toxicity value limits the information needed for making decisions and gives a false sense of precision and accuracy.
Cross-sectional analysis of pulsatile hemodynamics across the adult life span: reference values, healthy and early vascular aging: the Heinz Nixdorf Recall and the MultiGeneration Study.

BACKGROUND Pulsatile hemodynamics predict major cardiovascular events. We aimed to provide comprehensive population-based reference values and to compare different measures of pulsatile hemodynamics to define early vascular aging (EVA) as well as healthy vascular aging (HVA). METHODS In 2721 participants from the population-based Heinz Nixdorf Recall Study and the associated MultiGeneration Study, free from diabetes, cardiovascular disease, and antihypertensive drugs, we performed high-fidelity radial tonometry, calibrated waveforms with brachial blood pressures and processed them with a validated transfer function, pulse wave analysis, and wave separation analysis. Aortic pulse wave velocity (aoPWV) was estimated with a validated regression formula. HVA was defined as the lowest, EVA as the highest age-specific decile of central pulse pressure (cPP), backward wave amplitude, and aoPWV. RESULTS Overall, 56.4% of participants were female, age range 18-90 years. Brachial PP increased from middle age, whereas cPP increased across the entire adult life span. Wave reflections increased across all age groups, apart from a plateau in older male participants. Indices of wave reflection were higher in women than in men. AoPWV showed the most prominent rise with age in both sexes. EVA and HVA, defined by cPP and backward wave amplitude, differed mainly by hemodynamic variables. In contrast, EVA participants were characterized by a worse hemodynamic, anthropometric, metabolic, and inflammatory profile, if aoPWV was used to discriminate EVA and HVA. CONCLUSION Age-specific and sex-specific reference values for central pulsatile hemodynamics in a general white population cohort are provided and may be utilized to define HVA and EVA.
The lysosomal aminopeptidase tripeptidyl peptidase 1 displays increased activity in malignant pancreatic cysts

Abstract Incidental detection of pancreatic cysts has increased dramatically over the last decade, but risk stratification and clinical management remain a challenge. Mucinous cysts are precursor lesions to pancreatic cancer, however, the majority are indolent. Current diagnostics cannot identify mucinous cysts that harbor cancer or reliably differentiate these lesions from nonmucinous cysts, which present minimal risk of malignant progression. We previously determined that activity of two aspartyl proteases was increased in mucinous cysts. Using a global protease activity profiling technology, termed multiplex substrate profiling by mass spectrometry (MSP-MS), we now show that aminopeptidase activity is also elevated in mucinous cysts. The serine aminopeptidase, tripeptidyl peptidase 1 (TPP1), was detected by proteomic analysis of cyst fluid samples and quantitation using targeted MS demonstrated that this protease was significantly more abundant in mucinous cysts. In a cohort of 110 cyst fluid samples, TPP1 activity was increased more than 3-fold in mucinous cysts relative to nonmucinous cysts. Moreover, TPP1 activity is primarily associated with mucinous cysts that harbor high-grade dysplasia or invasive carcinoma. Although only 59% accurate for differentiating these lesions, measurement of TPP1 activity may improve early detection and treatment of high-risk pancreatic cysts when used in conjunction with other promising biomarkers.
The dromedary camel displays annual variation in hypothalamic kisspeptin and Arg–Phe‐amide‐related peptide‐3 according to sex, season, and breeding activity

The dromedary camel (Camelus dromedarius) is a desert mammal whose cycles in reproductive activity ensure that the offspring's birth and weaning coincide with periods of abundant food resources and favorable climate conditions. In this study, we assessed whether kisspeptin (Kp) and arginine–phenylalanine (RF)‐amide related peptide‐3 (RFRP‐3), two hypothalamic peptides known to regulate the mammalian hypothalamo‐pituitary gonadal axis, may be involved in the seasonal control of camel's reproduction. Using specific antibodies and riboprobes, we found that Kp neurons are present in the preoptic area (POA), suprachiasmatic (SCN), and arcuate (ARC) nuclei, and that RFRP‐3 neurons are present in the paraventricular (PVN), dorsomedial (DMH), and ventromedial (VMH) hypothalamic nuclei. Kp fibers are found in various hypothalamic areas, notably the POA, SCN, PVN, DMH, VMH, supraoptic nucleus, and the ventral and dorsal premammillary nucleus. RFRP‐3 fibers are found in the POA, SCN, PVN, DMH, VMH, and ARC. POA and ARC Kp neurons and DMH RFRP‐3 neurons display sexual dimorphism with more neurons in female than in male. Both neuronal populations display opposed seasonal variations with more Kp neurons and less RFRP‐3 neurons during the breeding (December–January) than the nonbreeding (July–August) season. This study is the first describing Kp and RFRP‐3 in the camel's brain with, during the winter period lower RFRP‐3 expression and higher Kp expression possibly responsible for the HPG axis activation. Altogether, our data indicate the involvement of both Kp and RFRP‐3 in the seasonal control of the dromedary camel's breeding activity.
Interactions between a subset of substrate side chains and AAA+ motor pore loops determine grip during protein unfolding

Most AAA+ remodeling motors denature proteins by pulling on the peptide termini of folded substrates, but it is not well-understood how motors produce grip when resisting a folded domain. Here, at single amino-acid resolution, we identify the determinants of grip by measuring how substrate tail sequences alter the unfolding activity of the unfoldase-protease ClpXP. The seven amino acids abutting a stable substrate domain are key, with residues 2–6 forming a core that contributes most significantly to grip. ClpX grips large hydrophobic and aromatic side chains strongly and small, polar, or charged side chains weakly. Multiple side chains interact with pore loops synergistically to strengthen grip. In combination with recent structures, our results support a mechanism in which unfolding grip is primarily mediated by non-specific van der Waal’s interactions between core side chains of the substrate tail and a subset of YVG loops at the top of the ClpX axial pore.