Miracle-dz/UniFAR-FTUs huggingface dataset:
Ribodysgenesis: sudden genome instability in the yeast Saccharomyces cerevisiae arising from RNase H2 cleavage at genomic-embedded ribonucleotides

Abstract Ribonucleotides can be incorporated into DNA during replication by the replicative DNA polymerases. These aberrant DNA subunits are efficiently recognized and removed by Ribonucleotide Excision Repair, which is initiated by the heterotrimeric enzyme RNase H2. While RNase H2 is essential in higher eukaryotes, the yeast Saccharomyces cerevisiae can survive without RNase H2 enzyme, although the genome undergoes mutation, recombination and other genome instability events at an increased rate. Although RNase H2 can be considered as a protector of the genome from the deleterious events that can ensue from recognition and removal of embedded ribonucleotides, under conditions of high ribonucleotide incorporation and retention in the genome in a RNase H2-negative strain, sudden introduction of active RNase H2 causes massive DNA breaks and genome instability in a condition which we term ‘ribodysgenesis’. The DNA breaks and genome instability arise solely from RNase H2 cleavage directed to the ribonucleotide-containing genome. Survivors of ribodysgenesis have massive loss of heterozygosity events stemming from recombinogenic lesions on the ribonucleotide-containing DNA, with increases of over 1000X from wild-type. DNA breaks are produced over one to two divisions and subsequently cells adapt to RNase H2 and ribonucleotides in the genome and grow with normal levels of genome instability.
A pilot study of a single intermittent arm cycling exercise programme on people affected by Facioscapulohumeral dystrophy (FSHD)

For patients affected by Facioscapulohumeral dystrophy (FSHD), alternate methods for increasing physical activity engagement that may benefit shoulder function and wider health are needed. Arm cycling has been proposed as a potential method for achieving this although dosage parameters and evidence is limited. The aim of this study was to conduct a pilot study evaluating the effect of a single intermittent arm cycling exercise programme on people affected by FSHD. People with confirmed genetic diagnosis of FSHD between the ages 18–60 years were recruited to attend a single session for the exercise intervention (5 exercise efforts lasting 2 minutes each with 30 seconds of rest between each effort). Prior to exercise, measures of shoulder function (Oxford shoulder score), strength and range of movement were recorded. During the exercise participants were video recorded to quantify range of movement and extract movement profile features. Participants comments were recorded and followed up four days later to check for adverse events. Fifteen participants, (6F:9M) were recruited with median (IQR) Oxford Shoulder Scores of 25 (18 to 39). All participants successfully completed the exercise intervention with only transient symptoms consistent with exercise being reported and achieving a median (IQR) rate of perceived exertion scores of 13 (12 to 13). Movement profile data was available for 12 out of 15 participants and suggests that exercise intensity did not compromise movement. An association between strength and shoulder function (R2 = 0.5147), Rate of perceived exertion (RPE) of the final effort against shoulder function and strength (R2 = 0.2344 and 0.1743 respectively) was identified. Participant comments were positive regarding the exercise intervention. Our study demonstrates that an intermittent arm cycling programme is feasible for people affected by FSHD. Further work is needed to evaluate physiological responses to exercise across variations in programme variables and equipment set up in a larger sample of people affected by FSHD.
Safety and Effectiveness of COVID-19 Vaccines: Results from a Cross-Sectional Survey among Staff, Workers and Students at an Egyptian University

Mass vaccination is the most effective strategy against the spread of the COVID-19 pandemic. However, concerns about the vaccine’s safety and effectiveness remain a huge obstacle to vaccine acceptance. The aim of the present study was to explore different COVID-19 vaccine outcomes, including the development of adverse events and/or COVID-19 infection following COVID-19 vaccination. A cross-sectional study was conducted by distributing an online survey targeting staff and students at the British university in Egypt. A total of 637 participants fully completed the survey. Of these, 609 (95.6%) participants received the COVID-19 vaccine. Only 12.6% of the total vaccinated participants reported COVID-19 infection after vaccination. Of these, only 2.8% reported having severe symptoms while 9.9% reported having no or mild symptoms. The most common side effects reported after the first vs. second dose were headache (36.3% vs. 14.6%), tiredness and fatigue (26.9% vs. 10.7), and fever (25.6% vs. 6.7%). In conclusion, the present study explored different COVID-19 vaccine outcomes where the overall incidence of side effects is higher after the first dose than after the second dose. There is a relationship between COVID-19 vaccines’ side effects and gastrointestinal disorders, gender, and the type of COVID-19 vaccine. Post-vaccination symptoms were more frequently reported in women compared to men and more frequent with viral vector vaccines compared to other types. The effectiveness of different types of COVID-19 vaccines was confirmed by the lower incidence rate of post-vaccination COVID-19 infection.
Combining refutations and social norms increases belief change

Misinformed beliefs are difficult to change. Refutations that target false claims typically reduce false beliefs, but tend to be only partially effective. In this study, a social norming approach was explored to test whether provision of peer norms could provide an alternative or complementary approach to refutation. Three experiments investigated whether a descriptive norm—by itself or in combination with a refutation—could reduce the endorsement of worldview-congruent claims. Experiment 1 found that using a single-point estimate to communicate a norm affected belief but had less impact than a refutation. Experiment 2 used a verbally presented distribution of four values to communicate a norm, which was largely ineffective. Experiment 3 used a graphically presented social norm with 25 values, which was found to be as effective at reducing claim belief as a refutation, with the combination of both interventions being most impactful. These results provide a proof of concept that normative information can aid in the debunking of false or equivocal claims, and suggests that theories of misinformation processing should take social factors into account.
Network analysis of pig movements in Ecuador: Strengthening surveillance of classical swine fever.

The analysis of domestic pig movements has become useful to understand the disease spread patterns and epidemiology, which facilitates the development of more effective animal diseases control strategies. The aim of this work was to analyse the static and spatial characteristics of the pig network, to identify its trading communities and to study the contribution of the network to the transmission of classical swine fever. In this regard, we used the pig movement records from the National veterinary service of Ecuador (2017-2019), using social network analysis and spatial analysis to construct a network with registered premises as nodes and their movements as edges. Furthermore, we also created a network of parishes as its nodes by aggregating their premises movements as edges. The annual network metrics showed an average diameter of 20.33, a number of neighbours of 2.61, a shortest path length of 4.39 and a clustering coefficient of 0.38 (small-world structure). The most frequent movements were to or from markets (55%). Backyard producers made up 89% of the network premises, and the top 2% of parishes (highest degree) contributed to 50% of the movements. The highest frequencies of movements between parishes were in the centre of the country, while the highest frequency of movements to abattoirs was in the south-west. Finally, the pattern of CSF disease outbreaks within the Ecuador network was likely the result of network transmission processes. In conclusion, our results represented the first exploratory analysis of domestic pig movements at premise and parish levels. The surveillance system could consider these results to improve its procedures and update the disease control and management policy, and allow the implementation of targeted or risk-based surveillance. This article is protected by copyright. All rights reserved.
The portal vein in patients with cirrhosis is not an excessively inflammatory or hypercoagulable vascular bed, a prospective cohort study

A hypercoagulable state is not associated with development of portal vein thrombosis in cirrhosis, as we previously demonstrated. However, some groups demonstrated elevated levels of inflammatory markers and activation of hemostasis in the portal vein (PV) compared to posthepatic veins, but because the liver is involved in clearance of these markers, we hypothesize that interpretation of these data is not straightforward.
Epidemiological features and sociodemographic factors associated with mumps in mainland China from 2004 to 2018

Mumps is an acute infectious disease that spreads widely around the world. The aim of this study was to investigate the epidemiological features and sociodemographic factors associated with mumps in mainland China from 2004 to 2018. Incidence data for mumps during the period 2004–2018 were collected from the Public Health Sciences Data Center of China. Joinpoint regression analysis was performed to explore the trends of mumps. Space–time clustering analysis was conducted to spatial and temporal aggregation areas of mumps. A generalized linear model was used to explore sociodemographic factors associated with the incidence of mumps. The average annual incidence of mumps was 21.44/100 000 in mainland China. It was increased dramatically during 2004–2012 (annual percentage change [APC] = 7.51, 95% confidence interval [CI]: 2.28–13.00). After 2012, it remained stable, however, significantly increased in intermediately developed regions from 2015 to 2018 (APC = 25.84, 95% CI: 3.59–52.86). The first‐level spatial and temporal aggregation areas were distributed in Xinjiang, Gansu, Qinghai, Ningxia and Shaanxi, Tibet, Sichuan, Yunnan, Chongqing, Guizhou, and Guangxi, with gathering times from January 1, 2006 to December 31, 2012 (relative risk [RR] = 1.87, p < 0.001). The percentage of the population aged 0–14 years, number of health workers per capital, and number of passengers were found to be positively associated with the incidence of mumps. Overall, after 2012, the incidence of mumps in mainland China remained stable. High‐risk periods, clusters of regions, and sociodemographic factors for mumps were identified, which will help the government develop the disease‐ and location‐specific interventive measures.
Effect of Dietary Addition of Curcumin and Nano-Curcumin on Carcass Traits, Blood Haematology and Caecal Activity of Growing Rabbits Reared Under Heat Stress Conditions

The present study investigated the effects of dietary curcumin or nano-curcumin on carcass traits, caecum activity, caecum microbial count and haematological parameters of growing rabbits reared under heat stress conditions. APRI line growing rabbits (n=100, 5-wk of age) were distributed to five equal groups (n=20/group). Rabbits in the 1 st group were fed a control diet without any additives, whereas 2 nd , 3 rd , 4 th and 5 th groups were fed control diet supplemented with curcumin (25 or 50 mg), and nano-curcumin (2.5 or 5 mg)/kg diet up to 13-wk of age. Carcass traits, meat chemical composition, pH values of gastro-intestinal tract contents, caecum activity, caecum microbial counts, and haematological parameters were determined at 13-wk of age. The mean temperature-humidity index during the experimental period was 29.54. Results showed curcumin or nano-curcumin levels increased (P<0.05) count of red blood cell and platelets, and caecum activity parameters (ammonia nitrogen and volatile fatty acids), while reduced (P<0.05) white blood cells, total microbial and E. coli counts in the caecal content. Haematocrit value increased (P<0.05) only by nano-curcumin groups (2.5 or 5 mg/kg diet). Carcass traits, chemical composition of meat and pH values of gastro-intestinal tract contents were not significant among groups. Dietary curcumin or nano-curcumin levels, as natural antioxidants and growth promoters, can alleviate adverse impacts due to heat stress on caecal activity and health status without affecting the carcass traits of growing rabbits. Generally, the dietary addition of curcumin in nano-particles form could contribute to produce healthy and high-quality rabbit's meat for human consumption.
Epidemiology and estimated economic impact of musculoskeletal injuries in polytrauma patients in a level one trauma centre in Singapore

Introduction: Musculoskeletal injuries are the most common reason for surgical intervention in polytrauma patients. Methods: This is a retrospective cohort study of 560 polytrauma patients (injury severity score [ISS] >17) who suffered musculoskeletal injuries (ISS >2) from 2011 to 2015 in National University Hospital, Singapore. Results: 560 patients (444 [79.3%] male and 116 [20.7%] female) were identified. The mean age was 44 (range 3–90) years, with 45.4% aged 21–40 years. 39.3% of the patients were foreign migrant workers. Motorcyclists were involved in 63% of road traffic accidents. The mean length of hospital stay was 18.8 (range 0–273) days and the mean duration of intensive care unit (ICU) stay was 5.7 (range 0–253) days. Patient mortality rate was 19.8%. A Glasgow Coma Scale (GCS) score <12 and need for blood transfusion were predictive of patient mortality (p < 0.05); lower limb injuries, road traffic accidents, GCS score <8 and need for transfusion were predictive of extended hospital stay (p < 0.05); and reduced GCS score, need for blood transfusion and upper limb musculoskeletal injuries were predictive of extended ICU stay. Inpatient costs were significantly higher for foreign workers and greatly exceeded the minimum insurance coverage currently required. Conclusion: Musculoskeletal injuries in polytrauma remain a significant cause of morbidity and mortality, and occur predominantly in economically productive male patients injured in road traffic accidents and falls from height. Increasing insurance coverage for foreign workers in high-risk jobs should be evaluated.
Longitudinal Follow-Up of Gross Motor Function in Children with Congenital Zika Virus Syndrome from a Cohort in Rio de Janeiro, Brazil

Knowledge of how congenital Zika syndrome (CZS) impacts motor development of children longitudinally is important to guide management. The objective of the present study was to describe the evolution of gross motor function in children with CZS in a Rio de Janeiro hospital. In children with CZS without arthrogryposis or other congenital osteoarticular malformations who were followed in a prospective cohort study, motor performance was evaluated at two timepoints using the Gross Motor Function Classification System (GMFCS) and the Gross Motor Function Measurement test (GMFM-88). Among 74 children, at the baseline evaluation, the median age was 13 (8–24) months, and on follow-up, 28 (24–48) months. According to GMFCS at the second timepoint, 6 children were classified as mild, 11 as moderate, and 57 as severe. In the GMFM-88 assessment, children in the severe group had a median score of 10.05 in the baseline evaluation and a follow-up score of 12.40, the moderate group had median scores of 25.60 and 29.60, and the mild group had median scores of 82.60 and 91.00, respectively. Although a small developmental improvement was observed, the motor impairment of children was mainly consistent with severe cerebral palsy. Baseline motor function assessments were predictive of prognosis.
Cost‐effectiveness of three internet‐based interventions for eating disorders: A randomized controlled trial

Abstract Objective The primary aim was assessing the cost‐effectiveness of an internet‐based self‐help program, expert‐patient support, and the combination of both compared to a care‐as‐usual condition. Method An economic evaluation from a societal perspective was conducted alongside a randomized controlled trial. Participants aged 16 or older with at least mild eating disorder symptoms were randomly assigned to four conditions: (1) Featback, an online unguided self‐help program, (2) chat or e‐mail support from a recovered expert patient, (3) Featback with expert‐patient support, and (4) care‐as‐usual. After a baseline assessment and intervention period of 8 weeks, five online assessments were conducted over 12 months of follow‐up. The main result constituted cost‐utility acceptability curves with quality‐of‐life adjusted life years (QALYs) and societal costs over the entire study duration. Results No significant differences between the conditions were found regarding QALYs, health care costs and societal costs. Nonsignificant differences in QALYs were in favor of the Featback conditions and the lowest societal costs per participant were observed in the Featback only condition (€16,741) while the highest costs were seen in the care‐as‐usual condition (€28,479). The Featback only condition had the highest probability of being efficient compared to the alternatives for all acceptable willingness‐to‐pay values. Discussion Featback, an internet‐based unguided self‐help intervention, was likely to be efficient compared to Featback with guidance from an expert patient, guidance alone and a care‐as‐usual condition. Results suggest that scalable interventions such as Featback may reduce health care costs and help individuals with eating disorders that are currently not reached by other forms of treatment. Public significance statement Internet‐based interventions for eating disorders might reach individuals in society who currently do not receive appropriate treatment at low costs. Featback, an online automated self‐help program for eating disorders, was found to improve quality of life slightly while reducing costs for society, compared to a do‐nothing approach. Consequently, implementing internet‐based interventions such as Featback likely benefits both individuals suffering from an eating disorder and society as a whole.
Differential perivascular microglial activation in the deep white matter in vascular dementia developed post‐stroke

With the hypothesis that perivascular microglia are involved as neuroinflammatory components of the gliovascular unit contributing to white matter hyperintensities on MRI and pathophysiology, we assessed their status in stroke survivors who develop dementia. Immunohistochemical and immunofluorescent methods were used to assess the distribution and quantification of total and perivascular microglial cell densities in 68 brains focusing on the frontal lobe WM and overlying neocortex in post‐stroke dementia (PSD), post‐stroke non‐dementia (PSND) and similar age control subjects. We primarily used CD68 as a marker of phagocytic microglia, as well as other markers of microglia including Iba‐1 and TMEM119, and the myeloid cell marker TREM2 to assess dementia‐specific changes. We first noted greater total densities of CD68+ and TREM2+ cells per mm2 in the frontal WM compared to the overlying cortex across the stroke cases and controls (p = 0.001). PSD subjects showed increased percentage of activated perivascular CD68+ cells distinct from ramified or primed microglia in the WM (p < 0.05). However, there was no apparent change in perivascular TREM2+ cells. Total densities of TREM2+ cells were only ~10% of CD68+ cells but there was high degree of overlap (>70%) between them in both the WM and the cortex. CD68 and Iba‐1 or CD68 and TMEM119 markers were colocalised by ~55%. Within the deep WM, ~30% of CD68+ cells were co‐localised with fragments of degraded myelin basic protein. Among fragmented CD68+ cells in adjacent WM of PSD subjects, >80% of the cells expressed cleaved caspase‐3. Our observations suggest although the overall repertoire of perivascular microglial cells is not changed in the parenchyma, PSD subjects accrue more perivascular‐activated CD68+ microglia rather than TREM2+ cells. This implies there is a subset of CD68+ cells, which are responsible for the differential response in perivascular inflammation within the gliovascular unit of the deep WM.
Broad Cross-Reactive IgA and IgG against Human Coronaviruses in Milk Induced by COVID-19 Vaccination and Infection

It is currently unclear if SARS-CoV-2 infection or mRNA vaccination can also induce IgG and IgA against common human coronaviruses (HCoVs) in lactating parents. Here we prospectively analyzed human milk (HM) and blood samples from lactating parents to measure the temporal patterns of anti-SARS-CoV-2 specific and anti-HCoV cross-reactive IgA and IgG responses. Two cohorts were analyzed: a vaccination cohort (n = 30) who received mRNA-based vaccines for COVID-19 (mRNA-1273 or BNT162b2), and an infection cohort (n = 45) with COVID-19 disease. Longitudinal HM and fingerstick blood samples were collected pre- and post-vaccination or, for infected subjects, at 5 time-points 14–28 days after confirmed diagnosis. The anti-spike(S) and anti-nucleocapsid(N) IgA and IgG antibody levels against SARS-CoV-2 and HCoVs were measured by multiplex immunoassay (mPlex-CoV). We found that vaccination significantly increased the anti-S IgA and IgG levels in HM. In contrast, while IgG levels increased after a second vaccine dose, blood and HM IgA started to decrease. Moreover, HM and blood anti-S IgG levels were significantly correlated, but anti-S IgA levels were not. SARS2 acute infection elicited anti-S IgG and IgA that showed much higher correlations between HM and blood compared to vaccination. Vaccination and infection were able to significantly increase the broadly cross-reactive IgG recognizing HCoVs in HM and blood than the IgA antibodies in HM and blood. In addition, the broader cross-reactivity of IgG in HM versus blood indicates that COVID-19 vaccination and infection might provide passive immunity through HM for the breastfed infants not only against SARS-CoV-2 but also against common cold coronaviruses.