Miracle-dz/UniFAR-FTUs huggingface dataset:
Avian auditory hair cell regeneration is accompanied by JAK/STAT-dependent expression of immune-related genes in supporting cells

ABSTRACT The avian hearing organ is the basilar papilla that, in sharp contrast to the mammalian cochlea, can regenerate sensory hair cells and thereby recover from deafness within weeks. The mechanisms that trigger, sustain and terminate the regenerative response in vivo are largely unknown. Here, we profile the changes in gene expression in the chicken basilar papilla after aminoglycoside antibiotic-induced hair cell loss using RNA-sequencing. We identified changes in gene expression of a group of immune-related genes and confirmed with single-cell RNA-sequencing that these changes occur in supporting cells. In situ hybridization was used to further validate these findings. We determined that the JAK/STAT signaling pathway is essential for upregulation of the damage-response genes in supporting cells during the second day after induction of hair cell loss. Four days after ototoxic damage, we identified newly regenerated, nascent auditory hair cells that express genes linked to termination of the JAK/STAT signaling response. The robust, transient expression of immune-related genes in supporting cells suggests a potential functional involvement of JAK/STAT signaling in sensory hair cell regeneration.
3D bioprinting of osteon-mimetic scaffolds with hierarchical microchannels for vascularized bone tissue regeneration

The integration of three-dimensional (3D) bioprinted scaffold’s structure and function for critical-size bone defect repair is of immense significance. Inspired by the basic component of innate cortical bone tissue—osteons, many studies focus on biomimetic strategy. However, the complexity of hierarchical microchannels in the osteon, the requirement of mechanical strength of bone, and the biological function of angiogenesis and osteogenesis remain challenges in the fabrication of osteon-mimetic scaffolds. Therefore, we successfully built mimetic scaffolds with vertically central medullary canals, peripheral Haversian canals, and transverse Volkmann canals structures simultaneously by 3D bioprinting technology using polycaprolactone and bioink loading with bone marrow mesenchymal stem cells and bone morphogenetic protein-4. Subsequently, endothelial progenitor cells were seeded into the canals to enhance angiogenesis. The porosity and compressive properties of bioprinted scaffolds could be well controlled by altering the structure and canal numbers of the scaffolds. The osteon-mimetic scaffolds showed satisfactory biocompatibility and promotion of angiogenesis and osteogenesis in vitro and prompted the new blood vessels and new bone formation in vivo. In summary, this study proposes a biomimetic strategy for fabricating structured and functionalized 3D bioprinted scaffolds for vascularized bone tissue regeneration.
Exploration of Methanomethylophilus alvus pyrrolysyl-tRNA synthetase activity in yeast

Archaeal pyrrolysyl-tRNA synthetases (PylRSs) have been used to genetically encode over 200 distinct noncanonical amino acids (ncAAs) in proteins in E. coli and mammalian cells. This vastly expands the range of chemical functionality accessible within proteins produced in these organisms. Despite these clear successes, explorations of PylRS function in yeast remains limited. In this work, we demonstrate that the Methanomethylophilus alvus PylRS (MaPylRS) and its cognate tRNACUA support the incorporation of ncAAs into proteins produced in S. cerevisiae using stop codon suppression methodologies. Additionally, we prepared three MaPylRS mutants originally engineered in E. coli and determined that all three were translationally active with one or more ncAAs, although with low efficiencies of ncAA incorporation in comparison to the parent MaPylRS. Alongside MaPylRS variants, we evaluated the translational activity of previously reported Methanosarcina mazei, Methanosarcina barkeri, and chimeric M. mazei and M. barkeri PylRSs. Using the yeast strain RJY100, and pairing these aaRSs with the M. barkeri tRNACUA, we did not observe any detectable stop codon suppression activity under the same conditions that produced moderately efficient ncAA incorporation with MaPylRS. The addition of MaPylRS to the orthogonal translation machinery toolkit in yeast potentially opens the door to hundreds of ncAAs that have not previously been genetically encodable using other aminoacyl-tRNA synthetase/tRNA pairs. Extending the scope of ncAA incorporation in yeast could powerfully advance chemical and biological research for applications ranging from basic biological discovery to enzyme engineering and therapeutic protein lead discovery.
Factors associated with left ventricular hypertrophy in children with sickle cell disease: results from the DISPLACE study

Cardiopulmonary complications remain a leading cause of morbidity and mortality in sickle cell disease (SCD). The overall goals of this study were to evaluate the relationship between left ventricular hypertrophy (LVH) and laboratory markers of hemolysis and determine the association between LVH and SCD-specific therapies (hydroxyurea and chronic red cell transfusion). Data from the DISPLACE (Dissemination and Implementation of Stroke Prevention Looking at the Care Environment) study cohort was used. LVH was defined based on the left ventricular mass indexed to the body surface area as left ventricular mass index >103.0 g/m2 for males and >84.2 g/m2 for females. There were 1,409 children included in the analysis and 20.3% had LVH. Results of multivariable analysis of LVH showed baseline hemoglobin levels were associated with the lower odds of having LVH (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.60– 0.84). The odds of LVH increases for every 1-year increase in age (OR: 1.07, 95% CI: 1.02-1.13). Similarly, the odds of LVH were lower among males than females (OR: 0.59, 95% CI: 0.38-0.93). The odds of LVH were higher among those on hydroxyurea compared to no therapy (OR: 1.83, 95% CI: 1.41–2.37). Overall results of the study showed that LVH occurs early in children with SCD and the risk increases with increasing age and with lower hemoglobin. Further, we found higher use of hydroxyurea among those with LVH, suggesting that the need for hydroxyurea conveys a risk of cardiovascular remodeling.
Effectiveness of miniscrew assisted rapid palatal expansion using cone beam computed tomography: A systematic review and meta-analysis

Objective This study aims to examine the effectiveness of miniscrew assisted rapid palatal expansion (MARPE) treatment in late adolescents and adult patients using cone-beam computed tomography (CBCT). Methods Literature search was conducted in five electronic databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) based on the PICOS keyword design focusing on MARPE. Out of the 18 CBCT screened outcomes, only nine parameters were sufficient for the quantitative meta-analysis. The parameters were classified into three main groups 1) skeletal changes, 2) alveolar change, and 3) dental changes. Heterogeneity test, estimation of pooled means, publication bias, sensitivity analysis and risk of bias assessment were also performed. Results Upon database searching, only 14 full-text articles were qualified from the 364 obtained results. Heterogeneity test indicated the use of the random-effects model. The pooled mean estimate were as follows 1) Skeletal expansion zygomatic width, 2.39 mm; nasal width, 2.68 mm; jugular width, 3.12 mm; and midpalatal suture at the posterior nasal spine and anterior nasal spine, 3.34 mm and 4.56 mm, respectively; 2) Alveolar molar width expansion, 4.80 mm; and 3) Dental expansion inter-canine width, 3.96 mm; inter-premolar width, 4.99 mm and inter-molar width, 5.99 mm. The percentage of expansion demonstrated a skeletal expansion (PNS) of 55.76%, alveolar molar width expansion of 24.37% and dental expansion of 19.87%. Conclusions In the coronal view, the skeletal and dental expansion created by MARPE was of the pyramidal pattern. MARPE could successfully expand the constricted maxilla in late adolescents and adult patients.
Optimising the management of childhood acute diarrhoeal disease using a rapid test-and- treat strategy and/or Lactobacillus reuteri DSM 17938: a multicentre, randomised, controlled, factorial trial in Botswana

Introduction The study aim was to determine if rapid enteric diagnostics followed by the provision of targeted antibiotic therapy (‘test-and-treat’) and/or Lactobacillus reuteri DSM 17938 would improve outcomes in children hospitalised in Botswana with acute gastroenteritis. Methods This was a multicentre, randomised, factorial, controlled, trial. Children aged 2–60 months admitted for acute non-bloody diarrhoea to four hospitals in southern Botswana were eligible. Participants were assigned to treatment groups by web-based block randomisation. Test-and-treat results were not blinded, but participants and research staff were blinded to L. reuteri/placebo assignment; this was dosed as 1×108 cfu/mL by mouth daily and continued for 60 days. The primary outcome was 60-day age-standardised height (HAZ) adjusted for baseline HAZ. All analyses were by intention to treat. The trial was registered at Clinicaltrials.gov. Results Recruitment began on 12 June 2016 and continued until 24 October 2018. There were 66 participants randomised to the test-and-treat plus L. reuteri group, 68 randomised to the test-and-treat plus placebo group, 69 to the standard care plus L. reuteri group and 69 to the standard care plus placebo group. There was no demonstrable impact of the test-and-treat intervention (mean increase of 0.01 SD, 95% CI −0.14 to 0.16 SD) or the L. reuteri intervention (mean decrease of 0.07 SD, 95% CI −0.22 to 0.08 SD) on adjusted HAZ at 60 days. Conclusions In children hospitalised for acute gastroenteritis in Botswana, neither a test-and-treat algorithm targeting enteropathogens, nor a 60-day course of L. reuteri DSM 17938, were found to markedly impact linear growth or other important outcomes. We cannot exclude the possibility that test-and-treat will improve the care of children with significant enteropathogens (such as Shigella) in their stool. Trial registration number NCT02803827.
The Multi-Caregiver Role and Its Relationship to Behavioral Adherence and Weight Among Treatment Engaged Black Women

Purpose To examine the relationship between the multiple caregiver role and its perceived barriers to self-care on behavioral adherence in a weight loss intervention. Design A secondary analysis of data from a behavioral weight loss intervention. Setting The study was conducted in two cohorts from March 2016 to February 2017 at the University of North Carolina at Chapel Hill. Subjects Eighty-one Black women with overweight/obesity (age = 48.4 ± 10.9 years [M ± SD], BMI = 36.4 ± 4.5 kg/m2 [M ± SD]). Measures Identification with the multiple caregiver role and barriers was assessed with the Multiple Caregiving Measurement Instrument. Weight was measured with a digital scale and height with a stadiometer. The Block food frequency questionnaire evaluated dietary intake. Moderate-to-vigorous physical activity (MVPA) was measured objectively with an accelerometer. Study adherence was measured by session attendance, self-weighing, and self-monitoring (diet and physical activity) frequency. Analysis Generalized linear models were used to examine the relationship between the multiple caregiver scales and the outcomes of interest, controlling for study arm, cohort, and income. Chi-square tests tested correlations. Results Greater identification with the multiple caregiver role was associated with decreased session attendance (β = −.56 [SE = .27], P < .05) and a trend towards weight gain (β = .36, [SE = .19], P = .07). Greater multiple caregiver barriers score predicted a decrease in fruit/vegetable intake (β = −.17 [SE = .07], P < .05). All regression results are unstandardized. Negative correlations between multiple caregiver barriers and MVPA (r = −.24, P = .06) and daily self-weighing (r = −.19, P = .10) approached significance. Conclusions Participants’ identification with multiple caregiving role and barriers can reduce adherence, behavior and weight change. Interventions to address Black women’s multiple roles and barriers during weight loss are needed to maximize outcomes.
Diminished Cellular Immunity and Executive Cognitive Functioning Among Middle-Aged and Elderly Adults

ABSTRACT Objective Within the field of psychoneuroimmunology, much attention has been given to immune dysregulation and its impact on cognitive functioning. Some of this work has focused on the association between high levels of basal proinflammatory cytokines and poorer performance on measures of executive functioning; however, effect sizes have been quite small in human studies. Methods We investigated whether Epstein-Barr virus (EBV) antibody titers, a marker of immune dysregulation related to cellular immunity, may be associated with executive functioning while also attempting to replicate prior studies using two markers of proinflammatory cytokine production (i.e., circulating and lipopolysaccharide [LPS]-stimulated cytokines [interleukin 6, interleukin 1β, interferon-γ]). A total of 71 community-dwelling adults (mean [standard deviation] age = 60.87 [6.26] years) who were seropositive for EBV infection participated in the study. Results Findings indicated that greater EBV antibody titers were associated with poorer performance on measures of the executive functions of inhibition (B = −2.36, standard error = 1.06, p = .028) and cognitive flexibility (B = −2.89, standard error = 1.13, p = .013) when including circulating and LPS-stimulated cytokines and other relevant covariates (i.e., age, sex, and body mass index) in linear regression analyses. Neither circulating nor LPS-stimulated cytokines were associated with performance on the cognitive tasks in the regression analyses. Conclusions These results suggest that EBV antibody titers may be an indicator of immune dysregulation that is more relevant to executive functioning performance than either circulating or stimulated proinflammatory cytokines among community-dwelling adults.
Fourth Dose of BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting

Abstract Background With large waves of infection driven by the B.1. 1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alongside evidence of waning immunity after the booster dose of coronavirus disease 2019 (Covid-19) vaccine, several countries have begun giving at-risk persons a fourth vaccine dose. Methods To evaluate the early effectiveness of a fourth dose of the BNT162b2 vaccine for the prevention of Covid-19–related outcomes, we analyzed data recorded by the largest health care organization in Israel from January 3 to February 18, 2022. We evaluated the relative effectiveness of a fourth vaccine dose as compared with that of a third dose given at least 4 months earlier among persons 60 years of age or older. We compared outcomes in persons who had received a fourth dose with those in persons who had not, individually matching persons from these two groups with respect to multiple sociodemographic and clinical variables. A sensitivity analysis was performed with the use of parametric Poisson regression. Results The primary analysis included 182,122 matched pairs. Relative vaccine effectiveness in days 7 to 30 after the fourth dose was estimated to be 45% (95% confidence interval [CI], 44 to 47) against polymerase-chain-reaction–confirmed SARS-CoV-2 infection, 55% (95% CI, 53 to 58) against symptomatic Covid-19, 68% (95% CI, 59 to 74) against Covid-19–related hospitalization, 62% (95% CI, 50 to 74) against severe Covid-19, and 74% (95% CI, 50 to 90) against Covid-19–related death. The corresponding estimates in days 14 to 30 after the fourth dose were 52% (95% CI, 49 to 54), 61% (95% CI, 58 to 64), 72% (95% CI, 63 to 79), 64% (95% CI, 48 to 77), and 76% (95% CI, 48 to 91). In days 7 to 30 after a fourth vaccine dose, the difference in the absolute risk (three doses vs. four doses) was 180.1 cases per 100,000 persons (95% CI, 142.8 to 211.9) for Covid-19–related hospitalization and 68.8 cases per 100,000 persons (95% CI, 48.5 to 91.9) for severe Covid-19. In sensitivity analyses, estimates of relative effectiveness against documented infection were similar to those in the primary analysis. Conclusions A fourth dose of the BNT162b2 vaccine was effective in reducing the short-term risk of Covid-19–related outcomes among persons who had received a third dose at least 4 months earlier. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.)
Microbial diversity and composition in acidic sediments of freshwater finfish culture ponds fed with two types of feed: a metagenomic approach

Microbial community profile associated with acidic pond sediments (APS) (pH = 3·0–4·5) of freshwater finfish aquaculture ponds (n = 8) was investigated. Sediment DNA extracted from the eight APS were subjected to high‐throughput sequencing of V3 and V4 regions which yielded 7236 operational taxonomic units (OTUs) at a similarity of 97%. Overall results showed higher proportion of bacterial OTUs than archaeal OTUs in all the APS. Euryarchaeota (23%), Proteobacteria (19%), Chloroflexi (17%), Crenarchaeota (5·3%), Bacteroidetes (4·8%), Nitrospirae (3·2%), Nanoarchaeaeota (3%) which together constituted 75% of the microbial diversity. At the genus level, there was high preponderance of methanogens namely Methanolinea (5·4%), Methanosaeta (4·5%) and methanotrops, Bathyarchaeota (5%) in APS. Moreover, the abundant phyla in the APS were not drastically affected by the administration of chicken slaughter waste (R‐group ponds) and commercial fish feed (C‐group ponds), since 67% of the OTUs generated remained common in the APS of both the groups of ponds. There was a minimal difference of 24–26% of OTUs between C‐group and R‐group ponds, suggesting the existence of a core microbial community in these ponds driven by acidic pH over the years. This study concludes that microbial diversity in pond sediment was influenced to a lesser extent by the addition of chicken slaughter waste but was majorly driven by acidic nature of the pond.
Lumbar malignant peripheral nerve sheath tumor: a rare case in a young patient

Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma that originates from peripheral nerves or from cells associated with the nerve sheath. We report the case of a 30yearold male patient with a history of neurofibromatosis type I (NF-1) and a MPNST located in the lumbar region. The mass was resecated but surgical margins weren’t clear. Recurrence of disease was observed after a few months. A close monitoring of subjects with NF-1 is crucial to diagnose MPNST at an earlier stage and allow a complete surgical resection (www.actabiomedica.it).
Deep learning – promises for 3D nuclear imaging: a guide for biologists

ABSTRACT For the past century, the nucleus has been the focus of extensive investigations in cell biology. However, many questions remain about how its shape and size are regulated during development, in different tissues, or during disease and aging. To track these changes, microscopy has long been the tool of choice. Image analysis has revolutionized this field of research by providing computational tools that can be used to translate qualitative images into quantitative parameters. Many tools have been designed to delimit objects in 2D and, eventually, in 3D in order to define their shapes, their number or their position in nuclear space. Today, the field is driven by deep-learning methods, most of which take advantage of convolutional neural networks. These techniques are remarkably adapted to biomedical images when trained using large datasets and powerful computer graphics cards. To promote these innovative and promising methods to cell biologists, this Review summarizes the main concepts and terminologies of deep learning. Special emphasis is placed on the availability of these methods. We highlight why the quality and characteristics of training image datasets are important and where to find them, as well as how to create, store and share image datasets. Finally, we describe deep-learning methods well-suited for 3D analysis of nuclei and classify them according to their level of usability for biologists. Out of more than 150 published methods, we identify fewer than 12 that biologists can use, and we explain why this is the case. Based on this experience, we propose best practices to share deep-learning methods with biologists.
Validity Evidence of Brazilian Portuguese Version of the Professional Fulfillment Index

Purpose The questionnaire “Professional Fulfillment Index” (PFI) was validated to assess emotional exhaustion, interpersonal disengagement, and professional achievement among physicians. This study presents the process of cross-cultural adaptation of the PFI to the Brazilian context. Design Analytical cross-sectional study carried out between July and October 2020. Settings: For conceptual equivalence, a panel of experts was constituted who conducted analyzes on the translation and back-translation processes from English to Brazilian Portuguese. Subjects For the operational equivalence, 432 physicians in the field of Occupational Medicine were invited. Measures They answered the PFI in an online platform. Analysis: Both exploratory and confirmatory factor analysis were performed to seek evidence of the hypothesized structure of PFI item responses. Reliability was assessed using three indicators. Results The Brazilian version can be considered similar to the original. Most of participants were female (57.6%) and mean age 49.6 years—SD 14.0. The mean time since graduation was 18.5 years—SD 9.67. Most of them had a full-time job (88.0%) and were trained through post-graduation courses 83.8%. The most frequent job task was to perform worker´s clinical evaluations (84.9%). Exploratory and confirmatory analyzes showed the adequacy of the items in measuring the instrument’s construct, with stability for use in other populations and samples. Conclusion The PFI was developed to evaluate positive and negative aspects of physicians’ role and performance. The process described in this article was the first cross-cultural adaptation of the questionnaire. The PFI can help in mapping potential risk situations for negative impacts on physicians’ occupational well-being and performance at work, in order to propose interventions that reduce exhaustion and expand professional fulfillment.