Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of a Moderate Exercise Program on Serum Markers of Bone Metabolism in Dogs

Simple Summary In this article, we investigate the long-term (four months) effects of a 25 min moderate-intensity treadmill exercise, three times per week, on serum markers of bone metabolism (bone alkaline phosphatase and osteocalcin as bone formation markers and C-terminal telopeptide as bone resorption marker) in dogs. Twenty healthy dogs (Labrador and Golden Retrievers), median age 16.2 (11.7–24.4) months underwent the exercise program. Blood samples were collected as a baseline, mid-term (after two months) and at the end of the study. The values of bone formation markers significantly decreased following two months of exercise program; after which, bone alkaline phosphatase increased while osteocalcin concentration continued to decrease towards the end of the study. Bone resorption marker did not significantly change through the exercise duration. In overall, moderate exercise resulted in no change in bone resorption, and a mild bone formation in young developing dogs. Abstract The beneficial effect of physical activity on the musculoskeletal health in dogs is well recognized, but the level of intensity, duration, and frequency of exercise is not fully described. Measurement of serum markers of bone metabolism (bone alkaline phosphatase and osteocalcin as bone formation markers and C-terminal telopeptide as bone resorption marker) during four months of organized moderate-intensity physical training in Labrador retriever and Golden retriever dogs aged between 11.7–24.4 months, showed variations of bone metabolism. Dogs were included in treadmill running sessions for 25 min, three times per week. Blood samples were taken at the beginning of the program (baseline), after two months (mid-term) and at the end of the study after four months. The values of bone alkaline phosphatase and osteocalcin significantly decreased following two months of exercise program. Bone alkaline phosphatase increased by the end of four-month training cycle, but did not reach baseline value. Osteocalcin levels continued to decrease towards the end of the study. C-terminal telopeptide concentrations did not significantly change throughout the study duration. The results of this study show that aerobic exercise of moderate-intensity caused an initial decrease in bone formation followed by an increase of bone alkaline phosphatase and a further decrease of osteocalcin concentration. The response of two formation markers can be explained by the different stage of osteoblast activity that they express. In summary, moderate exercise resulted in no change in bone resorption, and a mild bone formation in young developing dogs.
Efficient genome editing in filamentous fungi via an improved CRISPR‐Cas9 ribonucleoprotein method facilitated by chemical reagents

DNA double‐strand break (DSB) repair induced by the RNA‐programmed nuclease Cas9 has become a popular method for genome editing. Direct genome editing via Cas9‐CRISPR gRNA (guide RNA) ribonucleoprotein (RNP) complexes assembled in vitro has also been successful in some fungi. However, the efficiency of direct RNP transformation into fungal protoplasts is currently too low. Here, we report an optimized genome editing approach for filamentous fungi based on RNPs facilitated by adding chemical reagents. We increased the transformation efficiency of RNPs significantly by adding Triton X‐100 and prolonging the incubation time, and the editing efficiency reached 100% in Trichoderma reesei and Cordyceps militaris. The optimized RNP‐based method also achieved efficient (56.52%) homologous recombination integration with short homology arms (20 bp) and gene disruption (7.37%) that excludes any foreign DNA (selection marker) in T. reesei. In particular, after adding reagents related to mitosis and cell division, the further optimized protocol showed an increased ratio of edited homokaryotic transformants (from 0% to 40.0% for inositol and 71.43% for benomyl) from Aspergillus oryzae, which contains multinucleate spores and protoplasts. Furthermore, the multi‐target engineering efficiency of the optimized RNP transformation method was similar to those of methods based on in vivo expression of Cas9. This newly established genome editing system based on RNPs may be widely applicable to construction of genome‐edited fungi for the food and medical industries, and has good prospects for commercialization.
Evaluation of a successful fluoroquinolone restriction intervention among high-risk patients: A mixed-methods study

Objective We conducted a quality improvement initiative to restrict fluoroquinolone prescribing on two inpatient units housing high-risk patients and applied a human factors approach to understanding the barriers and facilitators to success of this intervention by front-line providers. Methods This was a mixed-methods, quasi-experimental study. This study was conducted on two inpatient units at a tertiary care academic medical center: the medical-surgical intensive care and abdominal solid organ transplant units. Unit-level data were collected retrospectively for 24 months pre- and post- fluoroquinolone restriction intervention, implemented in July 2016, for all admissions to the study units. Our restriction intervention required antimicrobial stewardship pre-approval for fluoroquinolone prescribing. We explored barriers and facilitators to optimal fluoroquinolone prescribing using semi-structured interviews attending, fellow and resident physicians, advanced practice providers and pharmacists on these units. Results Hospital-onset C. difficile infection did not decrease significantly, but fluoroquinolone use declined significantly from 111.6 to 19.8 days of therapy per 1000 patient-days without negatively impacting length of stay, readmissions or mortality. Third generation cephalosporin and aminoglycoside use increased post-restriction. Providers identified our institution’s strong antimicrobial stewardship program and pharmacy involvement in antimicrobial decision making as key facilitators of fluoroquinolone optimization and patient complexity, lack of provider education and organizational culture as barriers to optimal prescribing. Conclusions Fluoroquinolones can be safely restricted even among high-risk patients without negatively impacting length of stay, readmissions or mortality. Our study provides a framework for successful antimicrobial stewardship interventions informed by perceptions of front line providers.
Prepartum Fat Mobilization in Dairy Cows with Equal Body Condition and Its Impact on Health, Behavior, Milk Production and Fertility during Lactation

Simple Summary An excess of lipolysis and subsequent increase on non-esterified fatty acids concentrations may impair animal health, welfare, and productivity after calving. In this study, we evaluated the effect of fat mobilization in dairy cows with a recommended body condition score at the beginning of the close-up period on blood indicators of health, incidence of diseases, behavior, milk production, and fertility during postpartum. An increased fat mobilization in dairy cows with an equal body condition score modified the inflammatory and oxidative stress responses during the early postpartum without impairing their health status and fertility. Moreover, behavior and milk production were sensitive indicators that reflected the negative effects of the excess of prepartum fat mobilization through lactation. Abstract The objective of this study was to evaluate the effect of two levels of fat mobilization at the close-up period in dairy cows with an equal body condition score (BCS = 3.0) on the circulating concentrations of metabolic, inflammatory, and oxidative stress biomarkers, incidence of diseases, behavior, milk production, and fertility during the postpartum. Late-gestation multiparous Holstein cows (n = 59) with a body condition score of 3.0 (5-point scale) were enrolled at the beginning of the close-up period and then were followed during the entire lactation. Cows were retrospectively allocated into two groups: animals with prepartum non-esterified fatty acids concentration over 0.3 mmol/L were categorized as high fat mobilization (HFM) (n = 26), and below this threshold as low fat mobilization (LFM) (n = 33). Blood samples were collected 21 d before expected calving and once weekly for 3 wk postpartum in order to analyze β-hydroxybutirate, haptoglobin, fibrinogen, total proteins, and malondialdehyde. Health was observed daily for 21 d postpartum. Behavioral data was collected with an accelerometer and milk production and fertility were obtained from the farm records. An increased fat mobilization in dairy cows with equal BCS modified the inflammatory and oxidative stress responses during the early postpartum without impairing their health status and fertility. Moreover, milk production and behavior were markedly affected by excessive prepartum fat mobilization through lactation.
Paraspeckle components NONO and PSPC1 are not mislocalized from motor neuron nuclei in sporadic ALS

1 The Francis Crick Institute, London NW1 1AT, UK 2 Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, Queen Square, London, UK 3 NeuroResource, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, London, UK 4 UCL Genetics Institute, University College London, London WC1E 6BT, UK 5 Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan 6 Idiap Research Institute, Centre du Parc, Office 206, PO Box 592, CH-1920 Martigny, Switzerland
Prevalence and risk factors of Schistosoma mansoni infection among children under two years of age in Mbita, Western Kenya

Despite growing evidence that infants and very young children can be infected with schistosomes, the epidemiological features and risk factors are not well described in this age group. We aimed to assess the prevalence of S. mansoni infection in children under two years of age from a population with a known high burden of infection in school-aged children and adults and thus inform the need for interventions in this potentially vulnerable age group. In a cross-sectional study in Mbita Sub-county, along the east coast of Lake Victoria, Western Kenya, we enrolled 361 children aged 6–23 months. The prevalence of S. mansoni infection was detected using the Kato-Katz stool examination and a point-of-care test for urinary circulating cathodic antigen (POC-CCA) (Rapid Medical Diagnostics, Pretoria, South Africa). Three-hundred and five (305) children had complete data of whom 276 (90.5%, 95%CI: 86.6–93.5) children were positive for S. mansoni by the POC-CCA test, while 11 (3.6%, 95%CI: 1.8–6.4) were positive by the Kato-Katz method. All Kato-Katz positive cases were also positive by the POC-CCA test. In multivariable analysis, only geographical area, Rusinga West (AOR = 7.1, 95%CI: 1.4–35.2, P = 0.02), was associated with S. mansoni infection using Kato-Katz test. Independent associations for POC-CCA positivity included age, (12–17 months vs 6–11 months; AOR = 7.8, 95%CI: 1.8–32.6, P = 0.002) and breastfeeding in the previous 24 hours (AOR = 3.4, 95%CI: 1.3–9.0, P = 0.009). We found a potentially very high prevalence of S. mansoni infection among children under two years of age based on POC-CCA test results in Mbita Sub-county, Kenya, which if confirmed strongly supports the need to include infants in public health strategies providing universal prophylactic treatment in high burden settings. Further research is required to determine the accuracy of diagnostic tools to detect light infection among very young children and possible long-term health impacts.
Neural dynamics of cue reliability in perceptual decisions

To extract meaningful information from scenes, the visual system must combine local cues that can vary greatly in their degree of reliability. Here, we asked whether cue reliability mostly affects visual or decision-related processes, using visual evoked potentials (VEPs) and a model-based approach to identify when and where stimulus-evoked brain activity reflects cue reliability. Participants performed a shape discrimination task on Gaborized ellipses, while we parametrically and independently, varied the reliability of contour or surface cues. We modeled the expected behavioral performance as a linear function of cue reliability and established at what latencies and electrodes VEP activity reflected behavioral sensitivity to cue reliability. We found that VEPs were linearly related to the individual behavioral predictors at around 400 ms post-stimulus, at electrodes over parietal and lateral temporal cortex. The observed cue reliability effects were similar for variations in contour and surface cues. Notably, effects of cue reliability were absent at earlier latencies where visual shape information is typically reported, and also in data time-locked to the behavioral response, suggesting the effects are not decision-related. These results indicate that reliability of visual cues is reflected in late distributed perceptual processes.
Coevolution between Parasocial Interaction in Digital Media and Social Contact with LGBT People

ABSTRACT Using a mixed methods approach, this research focuses on the association between exposure to online LGBT-related content and direct contact with LGBT people. We found that online parasocial contact facilitates both offline and online social interaction with members of the LGBT community. Consistent with parasocial contact theory, we found a positive association between exposure to LGBT-related content in online news and on social media and attitudes toward LGBT people. Moreover, these attitudes partly mediated the association between parasocial contact in digital media and social contact. Such mediation was found for all types of parasocial contact (online news and social media) and all types of direct social contact (offline and online). We also found that uncertainty reduction, humanization, and crowdsourcing can be important facilitators for effective parasocial contact with minorities through digital media.
Pelvic ring reconstruction with segmental spinal instrumentation after complete type I pelvic resection

Internal hemipelvectomy is a complex procedure used to treat malignancy that involves the pelvis. Reconstruction of the pelvis after type I or type I/IV resection remains controversial due to high complication rates and debatable functional benefit. Modern reconstruction options may provide a rapid, intuitive, and reliable way to reconstitute the pelvic ring.
A rare bacterial RNA motif is implicated in the regulation of the purF gene whose encoded enzyme synthesizes phosphoribosylamine

The Fibro-purF motif is a putative structured noncoding RNA domain that was discovered previously in species of Fibrobacter by using comparative sequence analysis methods. An updated bioinformatics search yielded a total of only 30 unique-sequence representatives, exclusively found upstream of the purF gene that codes for the enzyme amidophosphoribosyltransferase. This enzyme synthesizes the compound 5-phospho-D-ribosylamine (PRA), which is the first committed step in purine biosynthesis. The consensus model for Fibro-purF motif RNAs includes a predicted three-stem junction that carries numerous conserved nucleotide positions within the regions joining the stems. This architecture appears to be of sufficient size and complexity for the formation of the ligand-binding aptamer portion of a riboswitch. In this study, we conducted biochemical analyses of a representative Fibro-purF motif RNA to confirm that the RNA generally folds according to the predicted consensus model. However, due to the instability of PRA, binding of this ligand candidate by the RNA could not be directly assessed. Genetic analyses were used to demonstrate that Fibro-purF motif RNAs regulate gene expression in accordance with predicted PRA concentrations. These findings indicate that Fibro-purF motif RNAs are genetic regulation elements that likely suppress PRA biosynthesis when sufficient levels of this purine precursor are present.
Assessing performance of pathogenicity predictors using clinically relevant variant datasets

Background Pathogenicity predictors are integral to genomic variant interpretation but, despite their widespread usage, an independent validation of performance using a clinically relevant dataset has not been undertaken. Methods We derive two validation datasets: an ‘open’ dataset containing variants extracted from publicly available databases, similar to those commonly applied in previous benchmarking exercises, and a ‘clinically representative’ dataset containing variants identified through research/diagnostic exome and panel sequencing. Using these datasets, we evaluate the performance of three recent meta-predictors, REVEL, GAVIN and ClinPred, and compare their performance against two commonly used in silico tools, SIFT and PolyPhen-2. Results Although the newer meta-predictors outperform the older tools, the performance of all pathogenicity predictors is substantially lower in the clinically representative dataset. Using our clinically relevant dataset, REVEL performed best with an area under the receiver operating characteristic curve of 0.82. Using a concordance-based approach based on a consensus of multiple tools reduces the performance due to both discordance between tools and false concordance where tools make common misclassification. Analysis of tool feature usage may give an insight into the tool performance and misclassification. Conclusion Our results support the adoption of meta-predictors over traditional in silico tools, but do not support a consensus-based approach as in current practice.
Evaluation of cytomegalovirus IgG avidity index in differentiation of primary infection from reactivation

Objective To distinguish primary infection of human cytomegalovirus(HCMV) from reinfection or reactivation by evaluation of IgG avidity index.Methods Anti-HCMV IgM and IgG were detected by ELISA and anti-HCMV IgG avidity index(AI) was determined by an incubation assay from plasma of 50 patients(including longitudinal specimens from 8 patients). HCMV DNA was detected by nested PCR after total DNA was extracted from leukocytes.Results High concentration of anti-HCMV IgG influenced the measurement of AI.Three out of the 4 cases with high IgM titer showed AI30%,and 15 out of 17(88.2%) cases negative for HCMV DNA and anti-HCMV IgM showed intermediate or high avidity.Two out of 8 cases were diagnosed to be primary infection based on the AI determined in the serial samples.Conclusions Anti-HCMV IgG AI determined based on the incubation assay can be used to distinguish primary infection of HCMV from reinfection or reactivation.
Is it Safe for Patients with Left Ventricular Assist Devices to Undergo Non-Cardiac Surgery?

Background and Objectives: Since the first use of ventricular assist devices (VADs) as bridge to recovery and bridge to cardiac transplantation in the early 1990s, significant technological advances have transformed VAD implantation into a routine destination therapy. With improved survival, many patients present for cardiac surgery for conditions not directly related to their permanent mechanical circulatory support. The aim of this study was to analyze the indications and outcomes of non-cardiac surgeries (NCSs) of left ventricular assist device (LVAD) patients in tertiary center. Material and Methods: We present a single-center experience after 151 LVAD implantations in 138 consecutive patients between 2012–2019 who had to undergo NCS during a follow-up period of 37 +/− 23.4 months on left ventricular assist device (LVAD). Results: A total of 105 procedures was performed in 63 LVAD recipients, resulting in peri-operative mortality of 3.8%. Twenty-five (39.7%) of patients underwent multiple surgeries. We found no significant difference in cumulative survival associated with the performed surgical interventions (p = 0.469). Conclusion: We demonstrated good overall clinical outcomes in LVAD patients undergoing NCS. With acceptable peri-operative mortality, NCS can be safely performed in LVAD patients on long-term support.
Molecular algorithms accurately predict decreased susceptibility to ceftriaxone in Neisseria gonorrhoeae.

Dear Editor, W e read with great interest the report by Pinto et al., detailing the first multidrug ceftriaxone-resistant Neisseria gonorrhoeae isolate in Portugal. Antimicrobial resistance in N. gonorrhoeae is a global health threat, as the pathogen has developed resistance to every class of antibiotic available. Currently, dual therapy with ceftriaxone and azithromycin is recommended by the World Health Organization, although ceftriaxone or cefixime monotherapy is used in some countries. We recently analyzed a global series of publicly available genetic data of N. gonorrhoeae isolates through October 15, 2019, and analyzed mutations in genes associated with ceftriaxone resistance. From that analysis, we proposed 4molecular algorithms to predict decreased susceptibility to ceftriaxone using a cut-point minimum inhibitory concentration (MIC) of 0.064 mg/L. An MIC breakpoint of 0.06 mg/L has been used previously to define decreased susceptibility to ceftriaxone, a midpoint between susceptibility and resistance. The proposed algorithms differ in whether they (1) include penA or non-penA genes (penB, ponA, mtrR) and (2) include penA mosaicism. Each was estimated to result in either high sensitivity or specificity with moderate complementary specificity and sensitivity. Antimicrobial susceptibility testing of the strain reported by Pinto et al. showed resistance to ceftriaxone (MIC, 0.19 mg/L) and is therefore considered decreased susceptible according to our breakpoint. Genetic characterization data provided in the report include G542S in a nonmosaic penA allele, G120K and A121D in penB, and L421P in ponA. Based on those results, 2 of our proposed algorithms are applicable. First, using our algorithm including penA and mosaicism (Fig. 1), we estimated that for nonmosaic penA strains with no alteration at L447 and at least 1 of G542S, P551L/S, or A501V/T, the sensitivity and
Self-Efficacy and Clinical Characteristics in Casual Gamers Compared to Excessive Gaming Users and Non-Gamers in Young Adults

This study investigated differences in the self-efficacy and clinical characteristics which were found relevant to addictive behaviors in young adults according to time spent gaming. To our knowledge, this is the first study to explore self-efficacy in casual gamers relative to patients with internet gaming disorder (IGD) and non-gamers. In total, 158 young adults participated in this study and were divided into three groups: excessive gamers, who were diagnosed with IGD based on the Diagnostic and Statistical Manual of Mental Disorder-fifth edition (DSM-5, n = 71); casual gamers, who played games regularly but did not meet the criteria for IGD (n = 37); and non-gamers/controls, who did not engage in gaming (n = 50). All participants completed self-administered questionnaires, including measures of self-efficacy and clinical features such as the Barratt Impulsiveness Scale, Beck Depression Inventory, Beck Anxiety Inventory, Behavioral Activation/Inhibition Systems, aggression, and psychosocial well-being. There were significant differences in the self-efficacy according to the extent of gaming (excessive gamers < casual gamers < non-gamers). In addition, aggression, impulsivity, depression, anxiety, level of stress, and behavioral inhibition system scores were significantly higher in excessive gamers than in casual gamers and non-gamers. These findings showed that individuals who spend more time playing games tend to have lower self-efficacy. Our study suggests that self-efficacy may protect against or constitute a risk of excessive gaming, particularly among casual gamers. It is necessary to pay attention to enhancing psychological well-being through self-efficacy to prevent addiction in young adult gamers.