Miracle-dz/UniFAR-FTUs huggingface dataset:
Addition of Caffeine to a Carbohydrate Feeding Strategy Prior to Intermittent Exercise

Abstract The ergogenic effect of caffeine is well established, although no investigations providing a high carbohydrate feeding strategy (pre-exercise meal=2 g/kg BM) co-ingested with caffeine exist for soccer. This investigation examines the effect of caffeine in addition to a pre-exercise carbohydrate meal and drink mid-way through a soccer simulation. Eight recreational soccer players completed an 85-minute soccer simulation followed by an exercise capacity test (Yo-yo Intermittent Endurance test level 2) on two occasions. Prior to exercise participants consumed a high carbohydrate meal, with placebo or 5 mg/kg BM-1 caffeine. No significant performance effect was identified (p=0.099) despite a 12.8% (109 m) improvement in exercise capacity following caffeine. Rates of carbohydrate and fat oxidation did not differ between conditions and nor were differences apparent for plasma glucose, fatty acids, glycerol, β-hydroxybutyrate (p>0.05). However, an increase in lactate was observed for caffeine (p=0.039). A significant condition effect on rating of perceived exertion was identified (p<0.001), with the overall mean for the protocol lowered to 11.7±0.9 au for caffeine compared to 12.8±1.3 au. Caffeine supplementation with a carbohydrate feeding strategy failed to affect metabolic and metabolite responses, although reductions in perception of exercise were observed. While a 12.8% increase in exercise capacity was noted the findings were not significant, possibly due to the small sample size.
Impact of Bacterial Toxins in the Lungs

Bacterial toxins play a key role in the pathogenesis of lung disease. Based on their structural and functional properties, they employ various strategies to modulate lung barrier function and to impair host defense in order to promote infection. Although in general, these toxins target common cellular signaling pathways and host compartments, toxin- and cell-specific effects have also been reported. Toxins can affect resident pulmonary cells involved in alveolar fluid clearance (AFC) and barrier function through impairing vectorial Na+ transport and through cytoskeletal collapse, as such, destroying cell-cell adhesions. The resulting loss of alveolar-capillary barrier integrity and fluid clearance capacity will induce capillary leak and foster edema formation, which will in turn impair gas exchange and endanger the survival of the host. Toxins modulate or neutralize protective host cell mechanisms of both the innate and adaptive immunity response during chronic infection. In particular, toxins can either recruit or kill central players of the lung’s innate immune responses to pathogenic attacks, i.e., alveolar macrophages (AMs) and neutrophils. Pulmonary disorders resulting from these toxin actions include, e.g., acute lung injury (ALI), the acute respiratory syndrome (ARDS), and severe pneumonia. When acute infection converts to persistence, i.e., colonization and chronic infection, lung diseases, such as bronchitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) can arise. The aim of this review is to discuss the impact of bacterial toxins in the lungs and the resulting outcomes for pathogenesis, their roles in promoting bacterial dissemination, and bacterial survival in disease progression.
Discussion on “Assessing the goodness of fit of logistic regression models in large samples: A modification of the Hosmer‐Lemeshow test” by Giovanni Nattino, Michael L. Pennell, and Stanley Lemeshow

This work was supported by the Marsden Fund (Award Num-ber E2987-3648) administrated by the Royal Society of NewZealand and also supported by grant RTI2018-100927-J-I00 administrated by Ministerio de Ciencia e Innovacion (MCI,Spain), by the Agencia Estatal de Investigacion (AEI, Spain),and by the European Regional Development Fund FEDER(FEDER, UE). We are grateful to Dr Louise McMillan for helpful comments.
Ceftazidime-Avibactam Resistance Mediated by the N346Y Substitution in Various AmpC β-Lactamases

Chromosomal and plasmid-borne AmpC cephalosporinases are a major resistance mechanism to β-lactams in Enterobacteriaceae and Pseudomonas aeruginosa. The new β-lactamase inhibitor avibactam effectively inhibits class C enzymes and can fully restore ceftazidime susceptibility. The conserved amino acid residue Asn346 of AmpC cephalosporinases directly interacts with the avibactam sulfonate. Disruption of this interaction caused by the N346Y amino acid substitution in Citrobacter freundii AmpC was previously shown to confer resistance to the ceftazidime-avibactam combination (CAZ-AVI). ABSTRACT Chromosomal and plasmid-borne AmpC cephalosporinases are a major resistance mechanism to β-lactams in Enterobacteriaceae and Pseudomonas aeruginosa. The new β-lactamase inhibitor avibactam effectively inhibits class C enzymes and can fully restore ceftazidime susceptibility. The conserved amino acid residue Asn346 of AmpC cephalosporinases directly interacts with the avibactam sulfonate. Disruption of this interaction caused by the N346Y amino acid substitution in Citrobacter freundii AmpC was previously shown to confer resistance to the ceftazidime-avibactam combination (CAZ-AVI). The aim of this study was to phenotypically and biochemically characterize the consequences of the N346Y substitution in various AmpC backgrounds. Introduction of N346Y into Enterobacter cloacae AmpC (AmpCcloacae), plasmid-mediated DHA-1, and P. aeruginosa PDC-5 led to 270-, 12,000-, and 79-fold decreases in the inhibitory efficacy (k2/Ki) of avibactam, respectively. The kinetic parameters of AmpCcloacae and DHA-1 for ceftazidime hydrolysis were moderately affected by the substitution. Accordingly, AmpCcloacae and DHA-1 harboring N346Y conferred CAZ-AVI resistance (MIC of ceftazidime of 16 μg/ml in the presence of 4 μg/ml of avibactam). In contrast, production of PDC-5 N346Y was associated with a lower MIC (4 μg/ml) since this β-lactamase retained a higher inactivation efficacy by avibactam in comparison to AmpCcloacae N346Y. For FOX-3, the I346Y substitution did not reduce the inactivation efficacy of avibactam and the substitution was highly deleterious for β-lactam hydrolysis, including ceftazidime, preventing CAZ-AVI resistance. Since AmpCcloacae and DHA-1 display substantial sequence diversity, our results suggest that loss of hydrogen interaction between Asn346 and avibactam could be a common mechanism of acquisition of CAZ-AVI resistance.
The role of organizational learning and resilience for change in building quality improvement capacity in primary care.

BACKGROUND The extent that organizational learning and resilience for the change process, that is, adaptive reserve (AR), is a component of building practice capacity for continuous quality improvement (QI) is unknown. PURPOSE The aim of the study was to examine the association of AR and development of QI capacity. METHODOLOGY One hundred forty-two primary care practices were evaluated at baseline and 12 months in a randomized trial to improve care quality. Practice AR was measured by staff survey along with a validated QI capacity assessment (QICA). We assessed the association of baseline QICA with baseline AR and both baseline and change in AR with change in QICA from 0 to 12 months. Effect modification by presence of QI infrastructure in parent organizations and trial arm was examined. RESULTS Mean QICA increased from 6.5 to 8.1 (p < .001), and mean AR increased from 71.8 to 73.9 points (p < .001). At baseline, there was a significant association between AR and QICA scores: The QICA averaged 0.34 points higher (95% CI [0.04, 0.64], p = .03) per 10-point difference in AR. There was a significant association between baseline AR and 12-month QICA-which averaged 0.30 points higher (95% CI [0.02, 0.57], p = .04) per 10 points in baseline AR. There was no association between changes in AR and the QICA from 0 to 12 months and no effect modification by trial arm or external QI infrastructure. CONCLUSIONS Baseline AR was positively associated with both baseline and follow-up QI capacity, but there was no association between change in AR and change in the QICA, suggesting AR may be a precondition to growth in QI capacity. PRACTICE IMPLICATIONS Findings suggest that developing AR may be a valuable step prior to undertaking QI-oriented growth, with implications for sequencing of development strategies, including added gain in QI capacity development from building AR prior to engaging in transformation efforts.
Facile Fabrication of High Performance Pen-Ink Decorated Textile Strain Sensor for Human Motion Detection.

Recently, wearable strain sensors have increasingly attracted much attention due to their potential applications in human motion detection and personal health monitoring. To date, it is still a challenge to fabricate flexible strain sensor with both comfort and high performance. In this study, we dip the commercially available spandex/polyamide fabric into common pen ink to prepare a textile strain sensor with good skin affinity. The textile strain sensor exhibits a high gauge factor (~ 62.9) and an excellent linearity (R2 ~ 0.99) in the strain range of 0 to 30%. Before and after washing, the sensor both exhibits high stability in more than 5000 cycles. Owing to the facile integration of the ink-decorated fabric on clothes, the sensor can be conveniently attached to the human body to monitor human motions, thus showing great potential in practical applications.
Rejoinder to “Assessing the goodness of fit of logistic regression models in large samples: A modification of the Hosmer‐Lemeshow test”

Rejoinder to “Assessing the goodness of fit of logistic regression models in large samples: A modification of the Hosmer-Lemeshow test” Giovanni Nattino1 Michael L. Pennell2 Stanley Lemeshow2 Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Ranica, Bergamo, Italy Division of Biostatistics, College of Public Health, Ohio State University, Columbus, Ohio Correspondence Giovanni Nattino, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Ranica, Bergamo, Italy. Email:giovanni.nattino@marionegri.it
Lunar cycle and psychiatric hospital admissions for schizophrenia: new findings from Henan province, China

ABSTRACT Objective: Findings on the effect of the lunar cycle on mental illness are conflicting. We investigated the association between the lunar cycle and a number of psychiatric presentations of schizophrenia and determined which subtypes were susceptible to lunar phases. Methods: We evaluated 13,067 patients admitted to Zhumadian Psychiatric Hospital between January 1, 2012, and December 31, 2017 (73 lunar cycles). Patients were retrospectively assigned to lunar phase based on their admission date: new moon +/− 1 day, first quarter +/− 1 day, full moon +/− 1 day, and third quarter +/− 1 day. The International Statistical Classification of Diseases, 10th revision (ICD-10), was used for diagnosis. We used a Chi-squared goodness of fit test to evaluate the distribution of admissions across the lunar phase and R*C Chi-squared tests to compare age, sex, birth season, and clinical subtype distributions by phase. We used multiple logistic regression to further identify the relationship between clinical subtype and lunar phase. Results: Psychiatric admissions for schizophrenia varied significantly across the lunar cycle (χ2 = 36.400, p< .0001), peaking in the first quarter, followed by the full moon, and lowest at the new moon. Using unspecified schizophrenia (F20.9) as reference, people with paranoid schizophrenia (F20.0) were more likely to be admitted in the full moon than in other phases (odds ratio: 1.157, 95% confidence interval: 1.040–1.286) (p < .05); other subtypes showed no admission differences during the four lunar phases (p > .05). Conclusions: Psychiatric admissions for schizophrenia show lunar periodicities. People with schizophrenia tend to be stable in the new moon, but their condition is easily aggravated during the first quarter and full moon. Patients with paranoid schizophrenia are more susceptible to deterioration at the full moon, so merit more attention and care from communities, families, and hospitals.
Effects of Boric Acid Ester Modified Magnesium Borate Whisker on the Mechanical Properties and Crystallization Kinetics of Polypropylene Composites

Polypropylene (PP) is notch sensitive and brittle under severe conditions of deformation, limiting wider range of its usage as a structural load-bearing polymer. Hence, in this work the magnesium borate whisker (MBw), with similar mechanical properties to carbon fiber but much less expensive than polycrystalline silicon carbide, was modified by boric acid ester (BAE) and then used to fabricate PP composites. The mechanical properties, morphology, and non-isothermal crystallization property of virgin PP, PP/MBw, and PP/BAE-MBw composites were studied through mechanical testing, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC), respectively. The non-isothermal crystallization data was analyzed via Mo, Kissinger, and Dobreva methods. The results reveal that the incorporation of BAE-MBw into PP matrix results in higher tensile strength and impact strength than those of virgin PP and PP/MBw composite. The activation energies based on Kissinger were 190.20 kJ/mol for virgin PP, 206.59 kJ/mol for PP/MBw, and 218.98 kJ/mol for PP/BAE-MBw. The nucleation activities of whiskers determined by the Dobreva model were 0.86 for PP/MBw and 0.75 for PP/BAE-MBw. As a result, the whiskers, especially the modified whiskers, act as active substrates to facilitate heterogeneous nucleation, which leads to an increase in crystallization rate.
A Phase 1 Study of SLC-0111, a Novel Inhibitor of Carbonic Anhydrase IX, in Patients With Advanced Solid Tumors

Supplemental Digital Content is available in the text. Objectives: SLC-0111 is an ureido-substituted benzenesulfonamide small molecule inhibitor of carbonic anhydrase IX. The objectives of this first-in-human Phase 1 study were to determine the safety and tolerability of SLC-0111 in patients with advanced solid tumors and to establish the recommended Phase 2 dose for future clinical investigations. Materials and Methods: Using a 3+3 design, dose escalation started at 500 mg oral daily dosing of SLC-0111 in cohort 1 and increased to 1000 and 2000 mg in cohorts 2 and 3. Drug-related adverse events (AEs) were monitored to determine safety and tolerability. Pharmacokinetic analyses assessed plasma concentrations of single and repeated doses of SLC-0111. RECIST 1.1 criteria were used to assess disease progression. Results: No dose-limiting toxicities were reported and patients dosed at ≤1000 mg exhibited fewer drug-related AEs ≥ grade 3 and fewer AEs such as nausea and vomiting, compared with the 2000-mg cohort. Forty-one percent of patients experienced dose interruptions or discontinuation and the majority (71%) of these occurred in the 2000-mg cohort. Mean Cmax and AUC(0-24) values for single doses were similar at the 1000-mg and 2000-mg dose levels. Mean Tmax and T1/2 values of SLC-0111 were similar after single and repeated dosing. Power-law analysis of Cmax and AUC0-24 showed that exposure to SLC-0111 was generally dose proportional. No objective responses were observed, but stable disease >24 weeks was observed in 2 patients. Conclusions: SLC-0111 was safe in patients with previously treated, advanced solid tumors. The safety and pharmacokinetic data support 1000 mg/d as the recommended phase 2 dose for SLC-0111.
Probing lasting cryoinjuries to oocyte-embryo transcriptome

Clinical applications of oocytes cryopreservation include preservation of future fertility of young cancer patients, substitution of embryo freezing to avoid associated legal and ethical issues, and delaying childbearing years. While the outcome of oocyte cryopreservation has recently been improved, currently used vitrification method still suffer from increased biosafety risk and handling issues while slow freezing techniques yield overall low success. Understanding better the mechanism of cryopreservation-induced injuries may lead to development of more reliable and safe methods for oocyte cryopreservation. Using the mouse model, a microarray study was conducted on oocyte cryopreservation to identify cryoinjuries to transcriptionally active genome. To this end, metaphase II (MII) oocytes were subjected to standard slow freezing, and then analyzed at the four-cell stage after embryonic genome activation. Non-frozen four-cell embryos served as controls. Differentially expressed genes were identified and validated using RT-PCR. Embryos produced from the cryopreserved oocytes displayed 200 upregulated and 105 downregulated genes, associated with the regulation of mitochondrial function, protein ubiquitination and maintenance, cellular response to stress and oxidative states, fatty acid and lipid regulation/metabolism, and cell cycle maintenance. These findings reveal previously unrecognized effects of standard slow oocyte freezing on embryonic gene expression, which can be used to guide improvement of oocyte cryopreservation methods.
Utilizing Osteocyte Derived Factors to Enhance Cell Viability and Osteogenic Matrix Deposition within IPN Hydrogels

Many bone defects arising due to traumatic injury, disease, or surgery are unable to regenerate, requiring intervention. More than four million graft procedures are performed each year to treat these defects making bone the second most commonly transplanted tissue worldwide. However, these types of graft suffer from a limited supply, a second surgical site, donor site morbidity, and pain. Due to the unmet clinical need for new materials to promote skeletal repair, this study aimed to produce novel biomimetic materials to enhance stem/stromal cell osteogenesis and bone repair by recapitulating aspects of the biophysical and biochemical cues found within the bone microenvironment. Utilizing a collagen type I–alginate interpenetrating polymer network we fabricated a material which mirrors the mechanical and structural properties of unmineralized bone, consisting of a porous fibrous matrix with a young’s modulus of 64 kPa, both of which have been shown to enhance mesenchymal stromal/stem cell (MSC) osteogenesis. Moreover, by combining this material with biochemical paracrine factors released by statically cultured and mechanically stimulated osteocytes, we further mirrored the biochemical environment of the bone niche, enhancing stromal/stem cell viability, differentiation, and matrix deposition. Therefore, this biomimetic material represents a novel approach to promote skeletal repair.
Vibrio fischeri siderophore production drives competitive exclusion during dual-species growth.

When two or more bacterial species inhabit a shared niche, often, they must compete for limited nutrients. Iron is an essential nutrient that is especially scarce in the marine environment. Bacteria can use the production, release, and re-uptake of siderophores, small molecule iron chelators, to scavenge iron. Siderophores provide fitness advantages to species that employ them by enhancing iron acquisition, and moreover, by denying iron to competitors incapable of using the siderophore-iron complex. Here, we show that cell-free culture fluids from the marine bacterium Vibrio fischeri ES114 prevent growth of other vibrio species. Mutagenesis reveals the aerobactin siderophore as the inhibitor. Our analysis reveals a gene, that we name aerE, encodes the aerobactin exporter, and LuxT is a transcriptional activator of aerobactin production. In co-culture, under iron-limiting conditions, aerobactin production allows V. fischeri ES114 to competitively exclude Vibrio harveyi, which does not possess aerobactin production and uptake genes. By contrast, V. fischeri ES114 mutants incapable of aerobactin production lose in competition with V. harveyi. Introduction of iutA, encoding the aerobactin receptor, together with fhuCDB, encoding the aerobactin importer are sufficient to convert V. harveyi into an "aerobactin cheater".
Vestibulo-ocular reflex gain and compensatory saccades in three semicircular canals by video head impulse test

Background and Aim: One of the tools for ass­essing the vestibulo-ocular reflex (VOR) is using video head impulse test (vHIT). In this test by placing the head at different angles and shaking the head, three semicircular canals of the vestibular system in each ear can be exami­ned separately. The purpose of this study was to investigate the relationship between the low and high velocities of the vHIT test with VOR and its compensatory saccades. Methods: The vHIT test was performed by an examiner in 49 normal individuals aged 23–39 at low and high velocities. All participants had normal hearing, visual, and vestibular systems. Results: Mean gains in the horizontal, anterior and posterior semicircular canals in the right ear respectively were 0.92, 1 and 0.90 and in the left ear 0.93, 0.99 and 0.95 for low velocity and 0.78, 0.92 and 0.79 in the right ear and 0.80, 0.85 and 0.86 in the left ear for high velocity. Also, the number of compensatory saccade at high velocity was higher than those at the low velocity and the latency of compensatory sacc­ade was lower at the higher velocity. Conclusion: In the vHIT test, VOR gain decreases at high velocity that is statistically significant. Also, compensatory saccades are more likely to occur at high velocity with sma­ller delay. Therefore, high-velocity vHIT test is not recommended for the purpose of examining the VOR gain and compensatory saccade.
Factor Structure and Measurement Invariance of the Alcohol Use Disorders Identification Test (AUDIT) in a Sample of Military Veterans with and without PTSD

Abstract Background: The Alcohol Use Disorders Identification Test (AUDIT) was developed as a screening tool for problematic alcohol use and an intervention framework to aid those who drink excessively. While the AUDIT is widely used with at-risk populations, such as military veterans, major gaps exist in the research literature regarding the construct validity of the AUDIT in military samples. Objectives: This study assessed the factor structure and measurement invariance of the AUDIT in a large sample of Canadian military veterans (N = 1669; 94.94% male). Methods: Exploratory factor analysis (EFA) was conducted using a random subsample (n = 825) to assess the underlying factor structure of the AUDIT. Confirmatory factor analysis (CFA), using the second subsample (n = 844), was used to cross-validate the factor structure revealed by EFA and compare it to other model variants. Finally, multigroup CFAs were conducted using the whole sample to further cross-validate the factor structure and examine measurement invariance in military veterans with and without clinical elevations in posttraumatic stress disorder (PTSD) symptoms. Results: Factor analyses revealed that a modified two-factor model provided a statistically better fit to the data compared to all other model variants; yet, the results did not confirm measurement invariance across military veterans with and without clinically significant symptoms of PTSD. Conclusions/Importance: The findings are in line with increasing evidence suggesting that two subscale scores should be calculated for the AUDIT. Results further suggest that care should be taken in interpreting AUDIT scores when PTSD symptoms are present for military veterans.