Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimating Transmission Parameters for Respiratory Syncytial Virus and Predicting the Impact of Maternal and Pediatric Vaccination.

BACKGROUND Respiratory syncytial virus (RSV) is a leading cause of respiratory tract illness in young children and a major cause of hospital admissions globally. METHODS Here we fit age-structured transmission models with immunity propagation to data from the Netherlands (2012-2017). Data included nationwide hospitalizations with confirmed RSV, general practitioner (GP) data on attendance for care from acute respiratory infection, and virological testing of acute respiratory infections at the GP. The transmission models, equipped with key parameter estimates, were used to predict the impact of maternal and pediatric vaccination. RESULTS Estimates of the basic reproduction number were generally high (R0 > 10 in scenarios with high statistical support), while susceptibility was estimated to be low in nonelderly adults (<10% in persons 20-64 years) and was higher in older adults (≥65 years). Scenario analyses predicted that maternal vaccination reduces the incidence of infection in vulnerable infants (<1 year) and shifts the age of first infection from infants to young children. CONCLUSIONS Pediatric vaccination is expected to reduce the incidence of infection in infants and young children (0-5 years), slightly increase incidence in 5 to 9-year-old children, and have minor indirect benefits.
Estimating hybridization rates in the wild: Easier said than done?

Hybridization has important effects on the evolutionary trajectories of natural populations but estimates of this process in the wild and at the individual‐level are lacking. Justyn et al. attempted to fill this gap using the citizen science database eBird but there are limitations to this approach. Here, we outline and directly test these limitations using literature searches, case studies, and a comparison between eBird and Birds of North America (BNA), a database that documents hybridization using the scientific literature. We use a hybrid zone between Lazuli and Indigo buntings to highlight the importance of considering geographic range when estimating rates of hybridization and two literature searches to show the importance of considering cryptic hybrids (those that cannot be identified using phenotypic traits) when quantifying these rates. We also use BNA and a case study of hybrid White‐faced and Glossy Ibises to show that citizen scientists are underreporting hybrids compared with experts. Justyn et al. highlighted an important gap in the literature, but their results likely represent the lower limit of hybridization between birds and a more nuanced interpretation of their results (e.g., considering extrinsic postzygotic selection) is needed.
Growth performance comparison of exclusively breastfed infants with partially breastfed and formula fed infants

Background Little consensus exists for growth performance of different feeding patterns in infancy. The objective of this study is to assess the growth performance of exclusively breastfed, partially breastfed and formula fed infants in China. Methods Data from a total of 109,052 infants aged 1-<12 months were collected from the 4th and 5th China National Surveys in 2005 and 2015. Feeding patterns were classified into three types for infants under 6 months of age: exclusive breastfeeding, partial breastfeeding and formula feeding. Exclusive breastfeeding refers to feeding exclusively from the mother’s own milk (bottle-feeding included). Results 34.0% and 43.9% of infants were exclusively breastfed and 41.5% and 36.3% were partially breastfed at 4-<6 months in 2005 and 2015 respectively. Exclusively breastfed infants were generally a little heavier than partially breastfed and formula fed infants aged 1-<6 months; however, there was not a significant statistical difference between continued breastfeeding and formula feeding infants aged 6-<12 months. No significant statistical difference for length was observed among the three groups for ages 1-<6 months; however, infants who were continued to be breastfed were a little shorter compared to those who were formula fed (ages 6-<12 months). For infants aged 1-<2 months there was not a substantial difference from the 2006 WHO growth standards; however, for infants aged 2-<12 months the average weight and length of different feeding infants in China were a little heavier and longer than the 2006 WHO growth standards. Conclusions Partial breastfed and formula fed infants were a little lighter than exclusively breastfed infants in the first half of the first year. Formula fed infants were a little longer than continued breastfed infants in the second half.
Funders’ data-sharing policies in therapeutic research: A survey of commercial and non-commercial funders

Background Funders are key players in supporting randomized controlled trial (RCT) data-sharing. This research aimed to describe commercial and non-commercial funders' data-sharing policies and to assess the compliance of funded RCTs with the existing data-sharing policies. Methods and findings Funders of clinical research having funded at least one RCT in the years 2016 to 2018 were surveyed. All 78 eligible non-commercial funders retrieved from the Sherpa/Juliet Initiative website and a random sample of 100 commercial funders selected from pharmaceutical association member lists (LEEM, IFPMA, EFPIA) and the top 100 pharmaceutical companies in terms of drug sales were included. Thirty (out of 78; 38%) non-commercial funders had a data-sharing policy with eighteen (out of 30, 60%) making data-sharing mandatory and twelve (40%) encouraging data-sharing. Forty-one (out of 100; 41%) of commercial funders had a data-sharing policy. Among funders with a data-sharing policy, a survey of two random samples of 100 RCTs registered on Clinicaltrial.gov, data-sharing statements were present for seventy-seven (77%, 95% IC [67%-84%]) and eighty-one (81% [72% - 88%]) of RCTs funded by non-commercial and commercial funders respectively. Intention to share data was expressed in 12% [7%-20%] and 59% [49%– 69%] of RCTs funded by non-commercial and commercial funders respectively. Conclusions This survey identified suboptimal performances of funders in setting up data-sharing policies. For those with a data-sharing policy, the implementation of the policy in study registration was limited for commercial funders and of concern for non-commercial funders. The limitations of the present study include its cross-sectional nature, since data-sharing policies are continuously changing. We call for a standardization of policies with a strong evaluation component to make sure that, when in place, these policies are effective.
Altered mastication adversely impacts morpho-functional features of the hippocampus: A systematic review on animal studies in three different experimental conditions involving the masticatory function

Recent results have established that masticatory function plays a role not only in the balance of the stomatognathic system and in the central motor control, but also in the trophism of the hippocampus and in the cognitive activity. These implications have been shown in clinical studies and in animal researches as well, by means of histological, biochemical and behavioural techniques. This systematic review describes the effects of three forms of experimentally altered mastication, namely soft-diet feeding, molar extraction and bite-raising, on the trophism and function of the hippocampus in animal models. Through a systematic search of PubMed, Embase, Web of Science, Scopus, OpenGray and GrayMatters, 645 articles were identified, 33 full text articles were assessed for eligibility and 28 articles were included in the review process. The comprehensiveness of reporting was evaluated with the ARRIVE guidelines and the risk of bias with the SYRCLE RoB tool. The literature reviewed agrees that a disturbed mastication is significantly associated with a reduced number of hippocampal pyramidal neurons in Cornu Ammonis (CA)1 and CA3, downregulation of Brain Derived Neurotrophic Factor (BDNF), reduced synaptic activity, reduced neurogenesis in the Dentate Gyrus (DG), glial proliferation, and reduced performances in behavioural tests, indicating memory impairment and reduced spatial orientation. Moreover, while the bite-raised condition, characterized by occlusal instability, is known to be a source of stress, soft-diet feeding and molar extractions were not consistently associated with a stress response. More research is needed to clarify this topic. The emerging role of chewing in the preservation of hippocampal trophism, neurogenesis and synaptic activity is worthy of interest and may contribute to the study of neurodegenerative diseases in new and potentially relevant ways.
Epigenetic Changes in Islets of Langerhans Preceding the Onset of Diabetes

The identification of individuals with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention. Here, we used a translational approach and prediction criteria to identify changes in DNA methylation visible before the development of T2D. Islets of Langerhans were isolated from genetically identical 10-week-old female New Zealand Obese mice, which differ in their degree of hyperglycemia and in liver fat content. The application of a semiexplorative approach identified 497 differentially expressed and methylated genes (P = 6.42e-09, hypergeometric test) enriched in pathways linked to insulin secretion and extracellular matrix-receptor interaction. The comparison of mouse data with DNA methylation levels of incident T2D cases from the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort, revealed 105 genes with altered DNA methylation at 605 cytosine-phosphate-guanine (CpG) sites, which were associated with future T2D. AKAP13, TENM2, CTDSPL, PTPRN2, and PTPRS showed the strongest predictive potential (area under the receiver operating characteristic curve values 0.62–0.73). Among the new candidates identified in blood cells, 655 CpG sites, located in 99 genes, were differentially methylated in islets of humans with T2D. Using correction for multiple testing detected 236 genes with an altered DNA methylation in blood cells and 201 genes in diabetic islets. Thus, the introduced translational approach identified novel putative biomarkers for early pancreatic islet aberrations preceding T2D.
Current status of oxacillin-susceptible mecA-positive Staphylococcus aureus infection in Shanghai, China: A multicenter study.

BACKGROUND Oxacillin-susceptible mecA-positive Staphylococcus aureus (OS-MRSA) represents an important issue, as its oxacillin susceptibility has contributed to misidentification by conventional susceptibility tests and consequently potential therapeutic failure, but limited data on the current status of OS-MRSA infection in Chinese hospitals are available. METHODS This multicenter study performed a battery of susceptibility tests and diagnostic tests for 956 S. aureus isolates from 10 hospitals, including automated susceptibility testing on VITEK 2, broth microdilution, disk diffusion, and detection of PBB2a, mecA gene and mecC gene. For all identified OS-MRSA, multi-locus sequence typing (MLST), together with spa typing, SCCmec typing and PVL detecting, was carried out. RESULTS OS-MRSA, most of which were from pediatric inpatients, represented 1.8% (17/956) of total isolates. Of these 17 OS-MRSA, 10 were ST59, followed by ST965 (3/17), and 11 carried SCCmec type IV, while 5 carried SCCmec type V, but only one was Panton-Valentine leucocidin (PVL)-positive, also, 16 had one or two point mutations within mecA promoter. OS-MRSA had inducible oxacillin resistance and significantly lower MDR (Multi-Drug Resistant) rate. We observed that the VITEK 2 system exhibited some deficiency in OS-MRSA detection, whereas cefoxitin disk diffusion was shown to be a reliable and cost-saving alternative and should be supplemented in detecting S. aureus with borderline oxacillin susceptible MICs. CONCLUSION This study has characterized phenotypically and molecularly OS-MRSA in China, and provided insights into more effective management of OS-MRSA.
Effects of a virtual group cycling experience on people living with dementia: A mixed method pilot study

Social isolation and sedentary behaviour are common in residential aged care facilities (also known as nursing homes or long-term care). Use of new technologies such as virtual and augmented reality are currently under investigation for their potential to provide exciting and engaging activities for older people in residential aged care facilities. However, there is limited evidence on whether these technologies can promote physical activity in a small group setting for people with cognitive impairment. Using mixed methods, we examined the use of a virtual cycling experience in a sample of 10 participants with cognitive impairment living in residential aged care facilities. In a randomised crossover design, participants engaged in a 25-minute, self-paced, facilitated seated virtual cycling experience and a time-matched seated physical activity session in groups of five. All participants completed a brief pre- and post-intervention mood questionnaire. Video analysis was used for both conditions to compare levels of environmental stimulation, apathy and engagement using both the Person–Environment Apathy Rating Scale and the Engagement of a Person with Dementia Scale. A thematic analysis of semi-structured interviews following the virtual cycling experience was also performed. No differences were observed between conditions for all outcomes except for environmental stimulation, where there was a lower response in the intervention than the control condition (p = 0.032). This was primarily driven by lower scores for the virtual cycling experience than control in physical accessibility (p = 0.012). Participants reported the virtual cycling experience to be immersive and challenging and reminisced about cycling earlier in life. The activity manager observed that the virtual cycling experience was an overall positive experience and emphasised benefits of safety screening and preparation prior to the activities. The findings of this study support the use of the virtual cycling experience as an immersive and engaging alternative to usual activities, which might encourage higher levels of physical activity in residential aged care facilities.
Alternative N-terminal regions of Drosophila myosin heavy chain II regulate communication of the purine binding loop with the essential light chain

We investigated the biochemical and biophysical properties of one of the four alternative exon-encoded regions within the Drosophila myosin catalytic domain. This region is encoded by alternative exons 3a and 3b and includes part of the N-terminal β-barrel. Chimeric myosin constructs (IFI-3a and EMB-3b) were generated by exchanging the exon 3–encoded areas between native slow embryonic body wall (EMB) and fast indirect flight muscle myosin isoforms (IFI). We found that this exchange alters the kinetic properties of the myosin S1 head. The ADP release rate (k-D) in the absence of actin is completely reversed for each chimera compared with the native isoforms. Steady-state data also suggest a reciprocal shift, with basal and actin-activated ATPase activity of IFI-3a showing reduced values compared with wild-type (WT) IFI, whereas for EMB-3b these values are increased compared with wild-type (WT) EMB. In the presence of actin, ADP affinity (KAD) is unchanged for IFI-3a, compared with IFI, but ADP affinity for EMB-3b is increased, compared with EMB, and shifted toward IFI values. ATP-induced dissociation of acto-S1 (K1k+2) is reduced for both exon 3 chimeras. Homology modeling, combined with a recently reported crystal structure for Drosophila EMB, indicates that the exon 3–encoded region in the myosin head is part of the communication pathway between the nucleotide binding pocket (purine binding loop) and the essential light chain, emphasizing an important role for this variable N-terminal domain in regulating actomyosin crossbridge kinetics, in particular with respect to the force-sensing properties of myosin isoforms.
Mechanical feedback-loop regulation of morphogenesis in plants

ABSTRACT Morphogenesis is a highly controlled biological process that is crucial for organisms to develop cells and organs of a particular shape. Plants have the remarkable ability to adapt to changing environmental conditions, despite being sessile organisms with their cells affixed to each other by their cell wall. It is therefore evident that morphogenesis in plants requires the existence of robust sensing machineries at different scales. In this Review, I provide an overview on how mechanical forces are generated, sensed and transduced in plant cells. I then focus on how such forces regulate growth and form of plant cells and tissues. Summary: This Review provides crucial insight into the recent mechanical models of morphogenesis, and the approaches used to predict and measure mechanical properties of the plant cell wall.
Efficacy, safety and immunological profile of combining rituximab with belimumab for adults with persistent or chronic immune thrombocytopenia: results from a prospective phase IIb trial

B-cell activating factor may be involved in the failure of B-cell depleting therapy with rituximab in immune thrombocytopenia (ITP) by promoting the emergence of splenic long-lived plasma cells. From results obtained in mouse models, we hypothesized that combining rituximab with sequential injections of belimumab could increase the rate of response at 1 year in patients with persistent or chronic ITP by preventing the emergence of these long-lived plasma cells. The study was a single-center, single-arm, prospective phase IIb trial investigating the safety and efficacy of rituximab given at a fixed dose of 1,000 mg, 2 weeks apart, combined with five infusions of belimumab, 10 mg/kg at week 0 (W0)+2 days, W2+2 days, W4, W8 and W12 for adults with primary persistent or chronic ITP. The primary endpoint was the total number of patients achieving an overall response (complete response + response) at W52 according to a standard definition. In total, 15 non-splenectomized adults, nine (60%) with persistent IPT and six (40%) with chronic ITP, were included. No severe adverse event, infection, or severe hypogammaglobulinemia was observed. Thirteen patients achieved an initial overall response. At W52, 12 (80%) patients achieved an overall response, including ten (66.7%) with complete response. When compared with a cohort of patients receiving rituximab alone, the kinetics of B-cell repopulation appeared similar, but the number of circulating T-follicular helper cells was significantly decreased with belimumab combination therapy. Combining rituximab and belimumab seems a promising strategy in ITP, with high efficacy and acceptable safety (clinicaltrials gov. Identifier: NCT03154385).
Root angle modifications by the DRO1 homolog improve rice yields in saline paddy fields

Significance Genetically improving the root system architectures of plants is an effective strategy for developing climate-resilient crops. In this study, we revealed that a cloned rice quantitative trait locus associated with root growth angle, qSOR1, is a DRO1 homolog involved in root gravitropic responses. The loss-of-function allele qsor1 resulted in roots that developed on the soil surface and enabled plants to avoid the reducing stress found in saline paddy soils and, consequently, increased yields. We show that the DRO1 homologs could be useful for the controlled breeding of root system architectures that are adapted to the abiotic stress conditions caused by global climate change. The root system architecture (RSA) of crops can affect their production, particularly in abiotic stress conditions, such as with drought, waterlogging, and salinity. Salinity is a growing problem worldwide that negatively impacts on crop productivity, and it is believed that yields could be improved if RSAs that enabled plants to avoid saline conditions were identified. Here, we have demonstrated, through the cloning and characterization of qSOR1 (quantitative trait locus for SOIL SURFACE ROOTING 1), that a shallower root growth angle (RGA) could enhance rice yields in saline paddies. qSOR1 is negatively regulated by auxin, predominantly expressed in root columella cells, and involved in the gravitropic responses of roots. qSOR1 was found to be a homolog of DRO1 (DEEPER ROOTING 1), which is known to control RGA. CRISPR-Cas9 assays revealed that other DRO1 homologs were also involved in RGA. Introgression lines with combinations of gain-of-function and loss-of-function alleles in qSOR1 and DRO1 demonstrated four different RSAs (ultra-shallow, shallow, intermediate, and deep rooting), suggesting that natural alleles of the DRO1 homologs could be utilized to control RSA variations in rice. In saline paddies, near-isogenic lines carrying the qSOR1 loss-of-function allele had soil-surface roots (SOR) that enabled rice to avoid the reducing stresses of saline soils, resulting in increased yields compared to the parental cultivars without SOR. Our findings suggest that DRO1 homologs are valuable targets for RSA breeding and could lead to improved rice production in environments characterized by abiotic stress.
Retinal Ganglion Cell Topography and Spatial Resolving Power in Echolocating and Non-Echolocating Bats

Bats are nocturnal mammals known for their ability to echolocate, yet all bats can see, and most bats of the family Pteropodidae (fruit bats) do not echolocate – instead they rely mainly on vision and olfaction to forage. We investigated whether echolocating bats, given their limited reliance on vision, have poorer spatial resolving power (SRP) than pteropodids and whether tongue click echolocating fruit bats differ from non-echolocating fruit bats in terms of visual performance. We compared the number and distribution of retinal ganglion cells (RGCs) as well as the maximum anatomical SRP derived from these distributions in 4 species of bats: Myotis daubentonii, a laryngeal echolocating bat from the family Vespertilionidae, Rousettus aegyptiacus, a tongue clicking echolocating bat from the family Pteropodidae, and Pteropus alecto and P. poliocephalus, 2 non-echolocating bats (also from the Pteropodidae). We find that all 3 pteropodids have a similar number (≈200,000 cells) and distribution of RGCs and a similar maximum SRP (≈4 cycles/degree). M. daubentonii has fewer (∼6,000 cells) and sparser RGCs than the pteropodids and thus a significantly lower SRP (0.6 cycles/degree). M. daubentonii also differs in terms of the distribution of RGCs by having a unique dorsal area of specialization in the retina. Our findings are consistent with the existing literature and suggest that M. daubentonii likely only uses vision for orientation, while for pteropodids vision is also important for foraging.