Miracle-dz/UniFAR-FTUs huggingface dataset:
Twin arginine translocation, ammonia incorporation, and polyamine biosynthesis are crucial for Proteus mirabilis fitness during bloodstream infection

The Gram-negative bacterium Proteus mirabilis is a common cause of catheter-associated urinary tract infections (CAUTI), which can progress to secondary bacteremia. While numerous studies have investigated experimental infection with P. mirabilis in the urinary tract, little is known about pathogenesis in the bloodstream. This study identifies the genes that are important for survival in the bloodstream using a whole-genome transposon insertion-site sequencing (Tn-Seq) approach. A library of 50,000 transposon mutants was utilized to assess the relative contribution of each non-essential gene in the P. mirabilis HI4320 genome to fitness in the livers and spleens of mice at 24 hours following tail vein inoculation compared to growth in RPMI, heat-inactivated (HI) naïve serum, and HI acute phase serum. 138 genes were identified as ex vivo fitness factors in serum, which were primarily involved in amino acid transport and metabolism, and 143 genes were identified as infection-specific in vivo fitness factors for both spleen and liver colonization. Infection-specific fitness factors included genes involved in twin arginine translocation, ammonia incorporation, and polyamine biosynthesis. Mutants in sixteen genes were constructed to validate both the ex vivo and in vivo results of the transposon screen, and 12/16 (75%) exhibited the predicted phenotype. Our studies indicate a role for the twin arginine translocation (tatAC) system in motility, translocation of potential virulence factors, and fitness within the bloodstream. We also demonstrate the interplay between two nitrogen assimilation pathways in the bloodstream, providing evidence that the GS-GOGAT system may be preferentially utilized. Furthermore, we show that a dual-function arginine decarboxylase (speA) is important for fitness within the bloodstream due to its role in putrescine biosynthesis rather than its contribution to maintenance of membrane potential. This study therefore provides insight into pathways needed for fitness within the bloodstream, which may guide strategies to reduce bacteremia-associated mortality.
Specific Collagen Peptides in Combination with Resistance Training Improve Body Composition and Regional Muscle Strength in Premenopausal Women: A Randomized Controlled Trial

The aim was to investigate the effects of resistance exercise combined with supplementation of specific collagen peptides (SCP) on body composition and muscle strength in premenopausal women. In a double-blind, placebo-controlled, randomized trial 77 premenopausal women completed a 12-week resistance training (3 day/week) and ingested 15 g of SCP or placebo on a daily basis. Changes in body composition were determined by bioelectrical impedance analysis (BIA) and muscular strength by isometric strength testing. The treatment group (TG) significantly increased (p < 0.001) their percentage of fat-free mass. Although the control group (CG) also showed a significant (p < 0.01) gain in fat-free mass from pre- to post-training, the increase in the TG was significantly higher in an RMANOVA analysis (p < 0.05). Regarding the change in percentage body fat, a significant decline was observed in both TG (p < 0.001) and CG (p < 0.01), with a significantly higher reduction in the TG (p < 0.05). Subjects receiving 15 g of collagen peptides daily also showed a significantly higher gain in hand-grip strength compared to those performing resistance training only (p < 0.05). In both groups, the gain in leg strength (TG = p < 0.001; CG = p < 0.01) was significant after 12 weeks with a more pronounced effect in the treatment group. In conclusion, resistance training in combination with supplementation of SCP induced a significantly higher increase in fat-free mass and hand-grip strength than resistance training and placebo supplementation. In addition, there was a significantly higher loss in fat mass and a more pronounced increase in leg strength in the treatment group compared to the control group.
Long-Term Conservation of Ohnologs Through Partial Tetrasomy Following Whole-Genome Duplication in Salmonidae

Whole-genome duplications (WGDs) have occurred repeatedly and broadly throughout the evolutionary history of eukaryotes. However, the effects of WGD on genome function and evolution remain unclear. The salmonid WGD that occurred approximately 88 million years ago presents an excellent opportunity for studying the effects of WGD as ∼10–15% of each salmonid genome still exhibits tetrasomic inheritance. Herein, we utilized the rainbow trout (Oncorhynchus mykiss) genome assembly and brain transcriptome data to examine the fate of gene pairs (ohnologs) following the salmonid whole-genome duplication. We find higher sequence identity between ohnologs located within known tetrasomic regions than between ohnologs found in disomic regions, and that tetrasomically inherited ohnologs showed greater similarity in patterns of gene expression and per ohnolog were lower expressed, than disomically inherited ohnologs. Enrichment testing for Gene Ontology terms identified 49 over-represented terms in tetrasomically inherited ohnologs compared to disomic ohnologs. However, why these ohnologs are retained as tetrasomic is difficult to answer. It could be that we have identified salmonid specific “dangerous duplicates”, that is, genes that cannot take on new roles following WGD. Alternatively, there may be adaptive advantages for retaining genes as functional duplicates in tetrasomic regions, as presumably, movement of these genes into disomic regions would affect both their sequence identity and their gene expression patterns.
Vagus nerve stimulation reverses the extinction impairments in a model of PTSD with prolonged and repeated trauma

Abstract We have shown that vagus nerve stimulation (VNS) enhances extinction of conditioned fear and reduces anxiety in rat models of PTSD using moderate stress. However, it is still unclear if VNS can be effective in enhancing extinction of severe fear after prolonged and repeated trauma. Severe fear was induced in adult male rats by combining single prolonged stress (SPS) and protracted aversive conditioning (PAC). After SPS and PAC procedures, rats were implanted with stimulating cuff electrodes, exposed to five days of extinction training with or without VNS, and then tested for extinction retention, return of fear in a new context and reinstatement. The elevated plus maze, open field and startle were used to test anxiety. Sham rats showed no reduction of fear during extensive extinction training. VNS-paired with extinction training reduced freezing at the last extinction session by 70% compared to sham rats. VNS rats exhibited half as much fear as shams, as well as less fear renewal. Sham rats exhibited significantly more anxiety than naive controls, whereas VNS rats did not. These results demonstrate that VNS enhances extinction and reduces anxiety in a severe model of PTSD that combined SPS and a conditioning procedure that is 30 times more intense than the conditioning procedures in previous VNS studies. The broad utility of VNS in enhancing extinction learning in rats and the strong clinical safety record of VNS suggest that VNS holds promise as an adjuvant to exposure-based therapy in people with PTSD and other complex forms of this condition.
The use of anthropometric measures in the prediction of incident gout: results from a Swedish community-based cohort study

Objectives: To study associations between different anthropometric measures and incident gout, and to find the best predictive measure. Method: We used the baseline investigation from the Malmö Diet and Cancer study, excluding cases of prevalent gout (n = 28 081). Cox regression for each anthropometric measurement was calculated per standard deviation increment for men and women, with hazard ratios (HRs) and 95% confidence intervals (CIs), using a hospital diagnosis of incident gout (M10) during follow-up as the outcome. Incremental C-statistics for each anthropometric measure were used to determine the measure with the best predictive capacity, in models adjusted for age, socio-economic data, lifestyle factors, comorbidities, and antihypertensive medications. Results: The study population included 11 049 men and 17 032 women, with 633 incident gout cases, 393 in men (3.6%) and 240 in women (1.4%). For both men and women, the five anthropometric measurements with highest C-statistics were weight, body mass index (BMI), waist circumference (WC), hip circumference, and waist-to-height ratio; in men, the measurement with the highest C-statistic was BMI (0.7361; fully adjusted HR 1.52, 95% CI 1.39–1.68), and in women WC (0.8085; fully adjusted HR 1.62, 95% CI 1.46–1.81). The increment in C-statistic with anthropometric measures was good, around 0.035. Waist-to-hip ratio, waist-to-hip-to-height ratio, body fat percentages, and especially A Body Shape Index had lower C-statistics. Conclusions: Both BMI and WC showed good predictive ability for incident gout. The clinically used cut-offs for BMI and WC appeared to be relevant in the assessment of increased risk of gout.
The role of hip abductor strength on the frontal plane of gait in subjects with medial knee osteoarthritis.

OBJECTIVE This study aimed to investigate the relationship of hip abductor strength with external hip and knee adduction moments, pain and physical function, and trunk, pelvis, and hip kinematics in the frontal plane during walking in subjects with medial knee osteoarthritis. METHODS Twenty-five subjects with medial knee osteoarthritis were evaluated through an isokinetic strength test for hip abductor, three-dimensional gait analysis (kinetics and kinematics), and pain and physical function scores. Regression models were used to control the influence of other parameters such as pain, age, gender, severity, walking speed, mass, and height. RESULTS No relationship was found of hip abductor strength with peak of external knee adduction moment and knee adduction angular impulse. Hip abductor strength explained 17% of contralateral pelvic drop and 21% of hip adduction angle. In addition, hip abductor strength explained 4% and 1% of the variance in the WOMAC physical function score and 40-m fast paced walk test, respectively. CONCLUSION Considering the relationship of hip abductor strength with contralateral pelvic drop and hip adduction angle, specific exercises might improve physical function and lower limb dynamic alignment during gait.
Managerial Ability and Dividend Payout Policy during Global Financial Crisis: Evidence from Emerging Market of China

In this paper, we examine the impact of pre-crisis managerial ability (MA) on firms' dividend policy during period of global financial crisis. By using data for 1640 non-financial listed firms of China, we document a strong positive relation between pre-crisis MA, dividend initiation decision (Di), and a negative relation between pre-crisis MA and dividend termination decision (Dt), that remains robust in the presence of corporate governance and CEO level control variables. We also analyze the impact of MA on dividend payout decisions (Dt, Di) by varying the construction of sample firms in two different ways, and find that relationship between MA and dividend payout decisions (Dt, Di) are 1) more prevalent for financially unconstrained firms and firms with strong balance sheet, 2) more pronounced under high marketized groups as compare to low marketized groups. Further, study confirms that di(dt) decision during crisis period increases(decreases) firm value. This study further employs propensity score matching (PSM) method to control possible endogeneity, and produce similar results.
Compensatory Growth of Scots Pine Seedlings Mitigates Impacts of Multiple Droughts Within and Across Years

Tree seedling resistance to and recovery from abiotic stressors such as drought and warming are crucial for forest regeneration and persistence. Selection of more resilient provenances and their use in forest management programs might alleviate pressures of climate change on forest ecosystems. Scots pine forests in particular have suffered frequent drought-induced mortality, suggesting high vulnerability to extreme events. Here, we conducted an experiment using potted Scots pine seedlings from ten provenances of its south-western distribution range to investigate provenance-specific impacts of multiple drought events. Seedlings were grown under ambient and elevated temperatures for 1.5 years and were subjected to consecutive droughts during spring and summer. Growth (height, diameter, and needle) and spring phenology were monitored during the whole study period and complemented by biomass assessments (bud, needle, wood, and needle/wood ratio) as well as measurements of chlorophyll fluorescence and of needle stable carbon isotope ratio. Phenology, growth and biomass parameters as well as carbon isotope ratio and their (direct) responses to reoccurring droughts differed between provenances, indicating genotypic adaptation. Seedling growth was plastic during drought with intra- and inter-annual compensatory growth after drought stress release (carryover effects), however, not fully compensating the initial impact. For (smaller) seedlings from southern/drier origins, sometimes greater drought resistance was observed which diminished under warmer conditions in the greenhouse. Warming increased diameter growth and advanced phenological development, which was (partly) delayed by drought in 2013, but advanced in 2014. Earlier phenology was linked to higher growth in 2013, but interestingly later phenology had positive effects on wood and needle biomass when subjected to drought. Lastly, stable carbon isotope ratios indicated a clear drought response of carbon assimilation. Drought-induced reduction of the photosystem II efficiency was only observed under warmer conditions but showed compensation under ambient temperatures. Besides these direct drought impacts, also interactive effects of previous drought events were shown, either reinforcing or sometimes attenuating the actual impact. Thus, depending on amount and timing of events, Scots pine seedlings, particularly from southern origins, might be well adapted and resilient to drought stress and should be considered when discussing assisted migration under changing climatic conditions.
Attitudes and Perceptions Toward Authorized Deception: A Pilot Comparison of Healthy Controls and Fibromyalgia Patients

Abstract Objective Little is known about the perceptions and attitudes of participants who volunteer in studies involving authorized deception. Thus, this cross-sectional pilot study measured, for the first time, the perceptions about participation in an authorized-deception placebo analgesia study in chronic pain patients with fibromyalgia and assessed whether their perceptions differed from healthy controls. Methods An anonymous survey with questions about trust in research and willingness to participate in future research involving deception was mailed to participants in both groups after completion of the parent study. Statistical analyses were performed using the Mann-Whitney U and chi-square tests (31 controls and 16 fibromyalgia patients were included in the analyses). Results The majority of participants expressed little or no concern about the deception, still trusted the scientific process, and found the debriefing procedure helpful and worthwhile. Group differences were found in willingness to 1) participate in the parent study had the deceptive element been disclosed in advance (controls = definitely, fibromyalgia patients = probably, U = 341.5, P = 0.01) and 2) participate in future studies (controls = definitely, fibromyalgia patients = probably, U = 373, P < 0.001). Conclusions Despite slightly less favorable responses of fibromyalgia patients and the relatively small size of the study, these findings suggest that attitudes and perceptions about participating in an authorized placebo study remain positive in both healthy and chronic pain populations.
An intervention including the national early warning score improves patient monitoring practice and reduces mortality: A cluster randomized controlled trial.

AIMS To investigate the impact of the national early warning score on the frequency and the quality of vital sign registration and to study the association between protocol compliance and patient mortality. DESIGN We conducted a post hoc data analysis of a stepped wedge cluster randomized controlled trial (RCT) in six hospitals. METHODS All adult, non-pregnant patients admitted to 24 wards were included. The intervention comprised an observation protocol using the national early warning score combined with a pragmatic medical response strategy. Data collection lasted from October 2013-May 2015. Patient comorbidity scores and vital signs were sampled every 4 months on each ward. All vital signs in the 24 hr before a serious adverse event were collected. RESULTS Patients (N = 60,956) were included of which 32,722 in the intervention group. Comorbidity scores were sampled in 3,600 patients and vital signs in 2,951 patients. In 668 patients, vital signs were collected before a serious adverse event. The mean number of vital signs per observation increased significantly in the intervention group. The observation frequency increased in patients with a serious adverse event and decreased in patients without a serious adverse event. Protocol compliance was negatively associated with patient mortality adjusted for comorbidity and age. CONCLUSION Our intervention improved patient monitoring practice and reduced mortality. IMPACT The impact of early warning scores on patient monitoring practice and patient outcomes remains unclear. Our intervention improved the observation of patients and reduced patient mortality. These results could support hospitals in their decision to implement rapid response systems. TRIAL REGISTRATION We have registered this study in the clinicaltrials.gov database (identifier: NCT01949025).
Associating Vehicles Automation With Drivers Functional State Assessment Systems: A Challenge for Road Safety in the Future

In the near future, vehicles will gradually gain more autonomous functionalities. Drivers’ activity will be less about driving than about monitoring intelligent systems to which driving action will be delegated. Road safety, therefore, remains dependent on the human factor and we should identify the limits beyond which driver’s functional state (DFS) may no longer be able to ensure safety. Depending on the level of automation, estimating the DFS may have different targets, e.g., assessing driver’s situation awareness in lower levels of automation and his ability to respond to emerging hazard or assessing driver’s ability to monitor the vehicle performing operational tasks in higher levels of automation. Unfitted DFS (e.g., drowsiness) may impact the driver ability respond to taking over abilities. This paper reviews the most appropriate psychophysiological indices in naturalistic driving while considering the DFS through exogenous sensors, providing the more efficient trade-off between reliability and intrusiveness. The DFS also originates from kinematic data of the vehicle, thus providing information that indirectly relates to drivers behavior. The whole data should be synchronously processed, providing a diagnosis on the DFS, and bringing it to the attention of the decision maker in real time. Next, making the information available can be permanent or intermittent (or even undelivered), and may also depend on the automation level. Such interface can include recommendations for decision support or simply give neutral instruction. Mapping of relevant psychophysiological and behavioral indicators for DFS will enable practitioners and researchers provide reliable estimates, fitted to the level of automation.
Periplasmic Nanobody-APEX2 Fusions Enable Facile Visualization of Ebola, Marburg, and Mĕnglà virus Nucleoproteins, Alluding to Similar Antigenic Landscapes among Marburgvirus and Dianlovirus

We explore evolved soybean ascorbate peroxidase (APEX2) as a reporter when fused to the C-termini of llama nanobodies (single-domain antibodies, sdAb; variable domains of heavy chain-only antibodies, VHH) targeted to the E. coli periplasm. Periplasmic expression preserves authentic antibody N-termini, intra-domain disulphide bond(s), and capitalizes on efficient haem loading through the porous E. coli outer membrane. Using monomeric and dimeric anti-nucleoprotein (NP) sdAb cross-reactive within the Marburgvirus genus and cross-reactive within the Ebolavirus genus, we show that periplasmic sdAb–APEX2 fusion proteins are easily purified at multi-mg amounts. The fusions were used in Western blotting, ELISA, and microscopy to visualize NPs using colorimetric and fluorescent imaging. Dimeric sdAb–APEX2 fusions were superior at binding NPs from viruses that were evolutionarily distant to that originally used to select the sdAb. Partial conservation of the anti-Marburgvirus sdAb epitope enabled the recognition of a novel NP encoded by the recently discovered Mĕnglà virus genome. Antibody–antigen interactions were rationalized using monovalent nanoluciferase titrations and contact mapping analysis of existing crystal structures, while molecular modelling was used to reveal the potential landscape of the Mĕnglà NP C-terminal domain. The sdAb–APEX2 fusions also enabled live Marburgvirus and Ebolavirus detection 24 h post-infection of Vero E6 cells within a BSL-4 laboratory setting. The simple and inexpensive mining of large amounts of periplasmic sdAb–APEX2 fusion proteins should help advance studies of past, contemporary, and perhaps Filovirus species yet to be discovered.
Sedentary Behaviour and 12 Sleep Problem Indicators among Middle-Aged and Elderly Adults in South Africa

The aim of this investigation was to assess the association of sedentary behaviour with 12 different sleep problem indicators among rural middle-aged and elderly adults in South Africa. Cross-sectional data were analysed from the “Health and Aging in Africa: A Longitudinal Study of an INDEPTH community in South Africa” (HAALSI) baseline survey. Participants responded to a questionnaire, including sociodemographic, health, anthropometric measures, sedentary behaviour and 12 different sleep problem indicators. The sample included 4782 individuals 40 years and older (median 61 years, interquartile range = 20 years). Overall, participants engaged <4 h (55.9%), 4–<8 h (34.1%), 8 or more hours a day (9.9%) sedentary time a day. In adjusted multinomial logistic regression, 8 h of more sedentary time was associated with short and long sleep. In adjusted logistic regression analysis, high sedentary time was positively associated with snoring, gasping, breathing stops and restless sleep and negatively associated with insufficient sleep and sleep problems due to a traumatic event. In combined analysis, compared to persons with low or moderate sedentary behaviour and moderate or high physical activity, persons with high sedentary behaviour and low physical activity were more likely to have long sleep, insufficient sleep, snoring, gasping, breathing stops, and restless sleep and less likely to have sleep problems due to traumatic events. Findings show an association between sedentary behaviour and/or combined sedentary behaviour and low physical activity with seven of 12 sleep problem indicators (short sleep, long sleep, insufficient sleep, snoring, gasping, breathing stops, and restless sleep).