Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrinsic and regulated properties of minimally edited trypanosome mRNAs

Abstract Most mitochondrial mRNAs in kinetoplastids require extensive uridine insertion/deletion editing to generate translatable open reading frames. Editing is specified by trans-acting gRNAs and involves a complex machinery including basal and accessory factors. Here, we utilize high-throughput sequencing to analyze editing progression in two minimally edited mRNAs that provide a simplified system due their requiring only two gRNAs each for complete editing. We show that CYb and MURF2 mRNAs exhibit barriers to editing progression that differ from those previously identified for pan-edited mRNAs, primarily at initial gRNA usage and gRNA exchange. We demonstrate that mis-edited junctions arise through multiple pathways including mis-alignment of cognate gRNA, incorrect and sometimes promiscuous gRNA utilization and inefficient gRNA anchoring. We then examined the roles of accessory factors RBP16 and MRP1/2 in maintaining edited CYb and MURF2 populations. RBP16 is essential for initiation of CYb and MURF2 editing, as well as MURF2 editing progression. In contrast, MRP1/2 stabilizes both edited mRNA populations, while further promoting progression of MURF2 mRNA editing. We also analyzed the effects of RNA Editing Substrate Binding Complex components, TbRGG2 and GAP1, and show that both proteins modestly impact progression of editing on minimally edited mRNAs, suggesting a novel function for GAP1.
All-cause mortality among young men 24–26 years after a lifestyle health dialogue in a Swedish primary care setting: a longitudinal follow-up register study

Objectives To compare mortality and socioeconomic status among men invited to a health dialogue with men from all of Sweden approximately 24 years after the start of the study, and to analyse the associations between lifestyle and all-cause mortality, incidence of cardiovascular disease (CVD) and cancer. Design Longitudinal follow-up register study of men 33–42 years old at baseline. Setting Primary care in a community in Sweden. Subjects All 757 men aged 33–42 years old in a community in southern Sweden, and 652 of these men who participated in a health examination between 1985 and 1987. Interventions Health examination, lifestyle-directed health dialogue and group activities in primary care in cooperation with local associations. Primary and secondary outcome measures All-cause mortality, income and educational level, and associations between lifestyle at baseline and all-cause mortality, incidence of CVD and cancer. Results At follow-up, all-cause mortality was 29% lower (OR=0.71, 95% CI 0.53 to 0.95) among all men invited to the health dialogue compared with all men from the same age cohort in all of Sweden (intention-to-treat) and 43% lower (OR=0.57, 95% CI 0.40 to 0.81) among participating men (on-treatment). A healthy lifestyle was associated with lower mortality (OR=0.16, 95% CI 0.07 to 0.36), with the strongest association for no smoking (OR=0.38, 95% CI 0.21 to 0.68) and a healthy diet (OR=0.37, 95% CI 0.20 to 0.68). A healthy lifestyle was also associated with a decreased incidence of CVD and cancer. There was a significantly higher proportion with short education among invited men compared with men from the same age cohort in all of Sweden. Conclusions This study indicates that a combination of low-risk and high-risk strategies, combining a health examination with a lifestyle-directed health dialogue conducted in an ordinary primary care setting in cooperation with local associations, may have contributed to reduced premature mortality. However, we cannot exclude that there may be other factors explaining the lower mortality.
Nutritional dual burden in Indigenous young adults: The geographical differential

OBJECTIVE Nutritional dual burden is defined as the coexistence of underweight and overweight in the same population. We report the rates of nutritional dual burden in Indigenous young men and women in the Northern Territory. Additionally, we examine the impact geographical area has on these rates. DESIGN Cross-sectional data obtained from the longitudinal Aboriginal Birth Cohort Study. SETTING Participants residing in over 40 urban and remote communities across the Top End of the Northern Territory. PARTICIPANTS Young adults aged 23-28 years; urban (n = 99) and remote (n = 316). MAIN OUTCOME MEASURE(S) Anthropometric data was directly collected using standardised methods. Underweight was defined as BMI ≤ 18.5 kg/m2 and overweight/obese as body mass index ≥ 25 kg/m2 . Remote residency was categorised by established shires/regions (Vic/Daly, Arnhem and Tiwi). RESULTS Significantly higher levels of underweight were seen in remote participants, compared to urban participants, irrespective of sex. Further differences were seen by regions, with the highest rates seen in Vic/Daly, compared to Arnhem and Tiwi. Higher rates of overweight/obesity were found in urban participants, compared to remote. The levels of overweight/obesity varied, depending on region of residence. CONCLUSION Underweight and overweight patterns coexist in Indigenous young adults, with variation across geographical regions. Health programs need to take this dual nutritional burden into consideration to avoid worsening the severity of underweight, whilst reducing levels of overweight.
Association of Surgical Intervention for Adhesive Small-Bowel Obstruction With the Risk of Recurrence.

Importance Adhesive small-bowel obstruction (aSBO) is a potentially chronic, recurring surgical illness. Although guidelines suggest trials of nonoperative management, the long-term association of this approach with recurrence is poorly understood. Objective To compare the incidence of recurrence of aSBO in patients undergoing operative management at their first admission compared with nonoperative management. Design, Setting, and Participants This longitudinal, propensity-matched, retrospective cohort study used health administrative data for the province of Ontario, Canada, for patients treated from April 1, 2005, through March 31, 2014. The study population included adults aged 18 to 80 years who were admitted for their first episode of aSBO. Patients with nonadhesive causes of SBO were excluded. A total of 27 904 patients were included and matched 1:1 by their propensity to undergo surgery. Factors used to calculate propensity included patient age, sex, comorbidity burden, socioeconomic status, and rurality of home residence. Data were analyzed from September 10, 2017, through October 4, 2018. Exposures Operative vs nonoperative management for aSBO. Main Outcomes and Measures The primary outcome was the rate of recurrence of aSBO among those with operative vs nonoperative management. Time-to-event analyses were used to estimate hazard ratios of recurrence while accounting for the competing risk of death. Results Of 27 904 patients admitted with their first episode of aSBO, 6186 (22.2%) underwent operative management. Mean (SD) patient age was 61.2 (13.6) years, and 51.1% (14 228 of 27 904) were female. Patients undergoing operative management were younger (mean [SD] age, 60.2 [14.3] vs 61.5 [13.4] years) with fewer comorbidities (low burden, 382 [6.2%] vs 912 [4.2%]). After matching, those with operative management had a lower risk of recurrence (13.0% vs 21.3%; hazard ratio, 0.62; 95% CI, 0.56-0.68; P < .001). The 5-year probability of experiencing another recurrence increased with each episode until surgical intervention, at which point the risk of subsequent recurrence decreased by approximately 50%. Conclusions and Relevance According to this study, operative management of the first episode of aSBO is associated with significantly reduced risk of recurrence. Guidelines advocating trials of nonoperative management for aSBO may assume that surgery increases the risk of recurrence putatively through the formation of additional adhesions. The long-term risk of recurrence of aSBO should be considered in the management of this patient population.
Facial distribution of squamous cell carcinoma in Japanese

Squamous cell carcinoma (SCC) is a malignant tumor of the skin. SCC is frequently distributed on highly exposed areas such as the face and dorsal surface of the hands because it is closely related to ultraviolet damage. We retrospectively analyzed 106 cases of SCC treated at Nagoya City University Hospital from April 2004 to October 2015 and examined regional features based on modified facial aesthetic units. SCC occurred more frequently on the cheek and forehead on the right side. The site of the tumor (nose and eyelid) was the only factor affecting tumor diameter.
Inquiry into short-term learning on Japanese rural islands: a qualitative study

ABSTRACT Background: Community-based medical education (CBME) improves the learning of medical students. The outcomes depend on the circumstances in which students learn. So far, there has been no study on the short-term learning experienced by medical students on rural islands in Japan; hence, we specifically explored this in the case of islands in Okinawa. Methods: We conducted one-on-one semi-structured interviews with seven medical students and three focus groups, each comprising three medical students. All subjects underwent a three-day clinical training on the rural islands of Okinawa, Japan. All sessions were audio-recorded and transcribed verbatim. We analysed the contents of the interview using the Steps for Coding and Theorisation. Results: Ten concepts were extracted and four themes generated: 1) rural resources and environments, 2) interaction with inhabitants, 3) rural physicians’ skills, and 4) proposed revisions. These themes and concepts provide valuable insights into the dynamics of medical care on rural islands as well as the benefit of this experience for students trained in urban contexts. The participants learned the importance of collaborating with multiple professionals in ways specific to each rural context. By interacting with various islanders, they developed an understanding of the different cultural backgrounds in which rural physicians work and their ability to adapt to each. This experience motivated them to pursue studies on rural medicine upon return to the mainland. Conclusion: This study shows that a short-term learning experience on rural islands in Japan may help medical students understand specific rural resources and their importance, the interconnections among the inhabitants, and the competency of primary care physicians.
Evolutionary and functional analyses of the interaction between the Bombyx mori inhibitor of apoptosis (IAP) and nucleopolyhedrovirus IAPs

As an important insect immune response, apoptosis plays a critical role in the interaction between baculoviruses and insect hosts. Previous reports have identified inhibitor of apoptosis (IAP) proteins in both insects and baculoviruses, but the relationship between these proteins is still not clearly understood. Here, we found that insect IAP proteins were clustered with baculovirus IAP3, suggesting that the baculovirus iap3 gene might be derived from the Lepidoptera or Diptera. We demonstrated that Bombyx mori inhibitor of apoptosis (Bmiap) gene had an inhibitory effect on apoptosis in silkworm cells. Further analysis of the effects of Bmiap genes on the proliferation of B. mori nucleopolyhedrovirus (BmNPV) showed that both the Bmiap and BmNPV iap genes increased BmNPV proliferation after BmNPV infected silkworm cells. Our results also indicated that BmNPV IAP1 and IAP2 directly interacted with BmIAP in silkworm cells, implying that the Bmiap gene might be hijacked by BmNPV iap genes during BmNPV infection. Taken together, our results provide important insights into the functional relationships of iap genes, and improve our knowledge of apoptosis in baculoviruses and insect hosts.
Differential gene expression analysis of sickle cell anemia in steady and crisis state

Sickle cell anemia is one of the most prevalent genetic diseases worldwide, showing great clinical heterogeneity. This study compared the gene expression patterns between sickle cell anemia pediatric patients in steady state and in crisis state, as compared to age‐paired, healthy individuals. RNA sequencing was performed from these groups of patients/controls using Illumina HiSeq 2500 equipment. The resulting differentially expressed genes were loaded into QIAGEN's ingenuity pathway analysis. The results showed that EIF2 pathway and NRF2‐mediated oxidative stress‐response pathways were more highly activated both in steady state and in crisis patients, as compared to healthy individuals. In addition, we found increased activation of eIF4 and p70S6K signaling pathways in crisis state compared to healthy individuals. The transcription factor GATA‐1 was found exclusively in steady state while SPI was found exclusively in crisis state. IL6 and VEGFA were found only in crisis state, while IL‐1B was found exclusively in steady state. The regulator effects analysis revealed IgG1 as an upstream regulator in steady state compared to healthy individuals, resulting in invasion of prostate cancer cell lines as the disease/function outcome. For crisis‐state patients versus healthy individuals, two networks of regulator effects revealed STAT1, CD40LG, TGM2, IRF7, IRF4, and IRF1 acting as upstream regulators, resulting in disease/function outcomes, including engulfment of cells and aggregation of blood cells and inflammation of joints. Our results indicated genes and pathways that can provide clues on the molecular events involved in the severity of sickle cell disease.
Enhancing Motor Competence and Physical Activity in Kindergarten.

BACKGROUND This study aimed at evaluating the effect of the "Walk," an 8-month physical activity (PA) program led by classroom and physical education teachers, on the motor competence (MC) and PA of 5- to 6-year-old children. METHODS A total of 143 children (mean age = 61.51 [1.85] mo) participated in the study and were randomly assigned to the experimental and control groups. Children's MC was assessed by the Körperkoordination Test für Kinder (KTK), and PA was objectively measured by Omron HJ-720IT-E2 pedometers. Measurements were performed at baseline, midintervention, and postintervention. A 1-sample t test computed at baseline step counts revealed that children presented significantly lower PA than recommended for their age (P < .001). To examine the effect of the intervention on children's MC and PA, several repeated-measures analyses of variance were utilized on (1) KTK item scores and (2) pedometer data. RESULTS The results revealed that the Walk project led to practically significant changes in the experimental group compared with the control group in both MC (P < .001, η2 > .14 for all KTK items) and PA (P < .001, η2 = .23). CONCLUSIONS This study highlights the efficacy of a PA project, involving both classroom and physical education teachers, for the enhancement of children's MC and PA.
Associations of the Mediterranean diet with cognitive and neuroimaging phenotypes of dementia in healthy older adults.

Background Accumulating evidence suggests that higher Mediterranean diet (MedDiet) adherence is associated with higher global cognitive performance and brain structural integrity as well as decreased risk of Alzheimer disease (AD) and vascular dementia (VaD). Objectives We directly examined cross-sectional associations between the MedDiet and cognitive and neuroimaging phenotypes associated with AD and VaD (separately) in a cohort of nondemented, nondepressed older adults. Methods Community-dwelling older adults (n = 82; aged ∼68.8 y; 50% female, 50% minority) underwent dietary (Block Food Frequency Questionnaire 2005) and neuropsychological assessments and neuroimaging. MedDiet scores were quantified with the use of published criteria, and participants were divided into High and Low (median split) adherence groups. We focused our neuropsychological investigation on cognitive phenotypes primarily associated with AD [i.e., learning and memory (L&M)] and VaD (i.e., information processing and executive functioning). AD neuroimaging phenotypes consisted of hippocampal and dentate gyrus volumes quantified using T1-weighted images and the FreeSurfer 6.0 segmentation pipeline (http://surfer.nmr.mgh.harvard.edu). The VaD neuroimaging phenotype consisted of total white matter hyperintensity (WMH) volumes quantified using combined T1-weighted and T2-fluid-attenuated inversion recovery images. Neuroimaging metrics were adjusted for total intracranial volume. Separate multivariable linear regression models controlling for age, sex, education, body mass index, and caloric intake examined the associations between MedDiet groups (High compared with Low) and cognitive and neuroimaging outcomes. Results When compared with the Low MedDiet group, the High MedDiet group was associated with better L&M performance and larger dentate gyri. MedDiet adherence was not associated with information processing, executive functioning, or WMH. Conclusion Results highlight the association between increasing MedDiet adherence and specific cognitive and neuroimaging phenotypes that, when altered, are associated with AD.
Chromium and cadmium removal from wastewater using duckweed - Lemna gibba L. and ultrastructural deformation due to metal toxicity

Abstract Phytoremediation potential of Lemna gibba was evaluated for chromium (Cr) and cadmium (Cd) under laboratory conditions for variable metal load of 1 mg/l, 3 mg/l, 5mgl, 7 mg/l and 9 mg/l, respectively, for 7 and 15 days of treatment period. Effects of both metals on structural attributes of L. gibba were also analyzed by Scanning Electron Microscopic (SEM) study. The metal removal percentage by L. gibba for Cr metal was found in the range of 37.3% to 98.6% and for cadmium it was found within the range of 81.6% to 94.6%. Bio concentration factor (BCF) of L . gibba was observed within the range of 37 to 295 for Cr metal and for Cd metal it ranged from 237 to 1144, which shows that the plant is a hyper accumulator for Cd metal and moderate accumulator for Cr metal. Statistical analysis (Two-way ANOVA) was performed on experimental results to confirm the individual effect of metal concentration and treatment period as well as cumulative effect of both factors together on percentage metal removal and on BCF. Research studies indicated that with the progress of treatment period metal removal percentage increases but increasing metal load during experiment negatively co-relates the metal removal percentage and BCF.
Effectiveness of interventions involving pharmacists on antibiotic prescribing by general practitioners: a systematic review and meta-analysis

Background The use of community antibiotic stewardship programmes (ASPs) is rising; however, their effectiveness when pharmacists are involved is uncertain. Objectives To assess the effectiveness of ASPs involving pharmacists at improving antibiotic prescribing by general practitioners (GPs). Methods Medline, Embase, Emcare, PubMed, PsycINFO, Cochrane CENTRAL, CINAHL Plus and Web of Science databases were searched to February 2018. Randomized and non-randomized studies of ASPs involving pharmacists as interventionists to GPs were included. Primary outcomes were absolute changes in GPs' antibiotic prescribing rate (APR) and antibiotic prescribing adherence rate (APAR) according to recommendations/guidelines. Meta-analysis used random effects models. Results Fifteen studies reporting 18 trials were included in the meta-analysis: 8 assessed the APR and 10 the APAR. APR reductions (OR 0.86, 95% CI 0.78-0.95, moderate-certainty evidence) and APAR improvements (OR 1.96, 95% CI 1.56-2.45, high-certainty evidence) were observed at 6 months median intervention follow-up. High-quality randomized trials reduced the APR (OR 0.92, 95% CI 0.90-0.94) and increased the APAR (OR 2.55, 95% CI 2.16-3.01). Interventions were successful in decreasing the APR (OR 0.93, 95% CI 0.90-0.95) and increasing the APAR (OR 1.72, 95% CI 1.04-2.84) when implemented by a pharmacist-GP team. Interventions involving pharmacist-infectious disease professional teams also decreased the APR (OR 0.81, 95% CI 0.66-1.0) and increased the APAR (OR 2.36, 95% CI 1.87-2.96). GP education plus prescribing feedback, and group meetings were effective in both outcomes, whereas GP education, academic detailing and workshop training were effective in APAR outcome. However, substantial heterogeneity was demonstrated. Conclusions ASPs involving pharmacists are effective in decreasing antibiotic prescribing and increasing guideline-adherent antibiotic prescribing by GPs.
Slow breathing improves cardiovascular reactivity to mental stress and health-related quality of life in heart failure patients with reduced ejection fraction.

BACKGROUND Previous studies have demonstrated therapeutic benefits of slow breathing (SLOWB) in chronic heart failure (HF) but its impact on cardiovascular reactivity in response to laboratory stressors remains unknown. METHODS Using device-guided breathing this study explored the acute and long-term effects of SLOWB on hemodynamic responses to handgrip, mental and cold pressor tests, and health-related quality of life (QoL) in stable HF patients with reduced ejection fraction (HFrEF) who had received all available optimal drug and device therapies. Blood pressure (BP) and heart rate (HR) were measured in 21 patients with HFrEF (23.9 ± 5.9%) at rest, during laboratory stressors, before and after acute SLOWB, and 12 weeks after SLOWB home training (30 min daily). Health-related QoL (MacNew questionaries) was assessed before and 12 weeks after SLOWB home training. RESULTS Resting BP significantly increased in response to three laboratory stressors. Pressor and cardiac changes during mental stress were greater than responses to the handgrip test (p < 0.05). Mental stress also produced a greater HR change than cold pressor test (p < 0.05). Both acute and long-term SLOWB significantly reduced BP and HR responses to mental stress (p < 0.05), but not to isometric and cold pressor tests. SLOWB improved scores of all domains of QoL (p < 0.05) at 12 week follow-up. CONCLUSIONS These findings demonstrate that SLOWB reduces acute and chronic effects of cardiovascular reactivity to mental stress and improves various aspects of health-related QoL in patients with severe HFrEF. Whether stress reduction and psychological changes achieved with SLOWB may translate to improved outcomes in HFrEF warrants further exploration.