Miracle-dz/UniFAR-FTUs huggingface dataset:
Single-cell RNA sequencing reveals transcriptional changes of human choroidal and retinal pigment epithelium cells during fetal development, in healthy adult and intermediate age-related macular degeneration

Abstract Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the developed world. Vision loss in the advanced stages of the disease is caused by atrophy of retinal photoreceptors, overlying retinal pigment epithelium (RPE) and choroidal endothelial cells. The molecular events that underline the development of these cell types from in utero to adult as well as the progression to intermediate and advanced stages AMD are not yet fully understood. We performed single-cell RNA-sequencing (RNA-Seq) of human fetal and adult RPE–choroidal tissues, profiling in detail all the cell types and elucidating cell type-specific proliferation, differentiation and immunomodulation events that occur up to midgestation. Our data demonstrate that progression from the fetal to adult state is characterized by an increase in expression of genes involved in the oxidative stress response and detoxification from heavy metals, suggesting a better defence against oxidative stress in the adult RPE–choroid tissue. Single-cell comparative transcriptional analysis between a patient with intermediate AMD and an unaffected subject revealed a reduction in the number of RPE cells and melanocytes in the macular region of the AMD patient. Together these findings may suggest a macular loss of RPE cells and melanocytes in the AMD patients, but given the complex processing of tissues required for single-cell RNA-Seq that is prone to technical artefacts, these findings need to be validated by additional techniques in a larger number of AMD patients and controls.
Mitochondrial stress and mitokines in aging

Mitokines are signaling molecules that enable communication of local mitochondrial stress to other mitochondria in distant cells and tissues. Among those molecules are FGF21, GDF15 (both expressed in the nucleus) and several mitochondrial‐derived peptides, including humanin. Their responsiveness to mitochondrial stress induces mitokine‐signaling in response for example to exercise, following mitochondrial challenges in skeletal muscle. Such signaling is emerging as an important mediator of exercise‐derived and dietary strategy‐related molecular and systemic health benefits, including healthy aging. A compensatory increase in mitokine synthesis and secretion could preserve mitochondrial function and overall cellular vitality. Conversely, resistance against mitokine actions may also develop. Alterations of mitokine‐levels, and therefore of mitokine‐related inter‐tissue cross talk, are associated with general aging processes and could influence the development of age‐related chronic metabolic, cardiovascular and neurological diseases; whether these changes contribute to aging or represent “rescue factors” remains to be conclusively shown. The aim of the present review is to summarize the expanding knowledge on mitokines, the potential to modulate them by lifestyle and their involvement in aging and age‐related diseases. We highlight the importance of well‐balanced mitokine‐levels, the preventive and therapeutic properties of maintaining mitokine homeostasis and sensitivity of mitokine signaling but also the risks arising from the dysregulation of mitokines. While reduced mitokine levels may impair inter‐organ crosstalk, also excessive mitokine concentrations can have deleterious consequences and are associated with conditions such as cancer and heart failure. Preservation of healthy mitokine signaling levels can be achieved by regular exercise and is associated with an increased lifespan.
DNA Methylation and RNA-DNA Hybrids Regulate the Single-Molecule Localization of a DNA Methyltransferase on the Bacterial Nucleoid

DNA methyltransferases (MTases) influence gene expression, cell cycle control, and host defense through DNA modification. Predicted MTases are pervasive across bacterial genomes, but the vast majority remain uncharacterized. ABSTRACT Bacterial DNA methyltransferases (MTases) function in restriction modification systems, cell cycle control, and the regulation of gene expression. DnmA is a recently described DNA MTase that forms N6-methyladenosine at nonpalindromic 5′-GACGAG-3′ sites in Bacillus subtilis, yet how DnmA activity is regulated is unknown. To address DnmA regulation, we tested substrate binding in vitro and found that DnmA binds poorly to methylated DNA and to an RNA-DNA hybrid with the DNA recognition sequence. Further, DnmA variants with amino acid substitutions that disrupt cognate sequence recognition or catalysis also bind poorly to DNA. Using superresolution fluorescence microscopy and single-molecule tracking of DnmA-PAmCherry, we characterized the subcellular DnmA diffusion and detected its preferential localization to the replisome region and the nucleoid. Under conditions where the chromosome is highly methylated, upon RNA-DNA hybrid accumulation, or with a DnmA variant with severely limited DNA binding activity, DnmA is excluded from the nucleoid, demonstrating that prior methylation or accumulation of RNA-DNA hybrids regulates the association of DnmA with the chromosome in vivo. Furthermore, despite the high percentage of methylated recognition sites and the proximity to putative endonuclease genes conserved across bacterial species, we find that DnmA fails to protect B. subtilis against phage predation, suggesting that DnmA is functionally an orphan MTase involved in regulating gene expression. Our work explores the regulation of a bacterial DNA MTase and identifies prior methylation and RNA-DNA hybrids as regulators of MTase localization. These MTase regulatory features could be common across biology. IMPORTANCE DNA methyltransferases (MTases) influence gene expression, cell cycle control, and host defense through DNA modification. Predicted MTases are pervasive across bacterial genomes, but the vast majority remain uncharacterized. Here, we show that in the soil microorganism Bacillus subtilis, the DNA MTase dnmA and neighboring genes are remnants of a phage defense system that no longer protects against phage predation. This result suggests that portions of the bacterial methylome may originate from inactive restriction modification systems that have maintained methylation activity. Analysis of DnmA movement in vivo shows that active DnmA localizes in the nucleoid, suggesting that DnmA can search for recognition sequences throughout the nucleoid region with some preference for the replisome. Our results further show that prior DNA methylation and RNA-DNA hybrids regulate DnmA dynamics and nucleoid localization, providing new insight into how DNA methylation is coordinated within the cellular environment.
Evidence for X-ray emission from superclusters of galaxies determined from Uhuru

We detect X-ray emission from three class 2 clusters of rich clusters of galaxies. Using a definition for these objects based in part on Abell's description, we find 12 candidate superclusters of distance class 5 and six clusters within the area of sky covered by the 4U catalog. The probability that these three X-ray sources accidentally coincide with the superclusters is less than 0.003. We find equally low probabilities that the X-ray emission is due to either a single luminous cluster or to the combined emission of all members of the supercluster. A possible explanation of these sources is thermal bremsstrahlung emission from a hot tenuous gas pervading the supercluster. The mass of the gas can be as much as 10 times the mass of the galaxies in the supercluster and comparable to the virial mass necessary to gravitationally bind the supercluster. Should such regions of enhanced gas density be found to be associated with all groups of clusters (multiplicity> or =2), then this gas may provide a significant fraction of the mass required to close the universe.
Postoperative Pulmonary Complications in the ENIGMA II Trial: A Post Hoc Analysis

Background: Nitrous oxide promotes absorption atelectasis in poorly ventilated lung segments at high inspired concentrations. The Evaluation of Nitrous oxide In the Gas Mixture for Anesthesia (ENIGMA) trial found a higher incidence of postoperative pulmonary complications and wound sepsis with nitrous oxide anesthesia in major surgery compared to a fraction of inspired oxygen of 0.8 without nitrous oxide. The larger ENIGMA II trial randomized patients to nitrous oxide or air at a fraction of inspired oxygen of 0.3 but found no effect on wound infection or sepsis. However, postoperative pulmonary complications were not measured. In the current study, post hoc data were collected to determine whether atelectasis and pneumonia incidences were higher with nitrous oxide in patients who were recruited to the Australian cohort of ENIGMA II. Methods: Digital health records of patients who participated in the trial at 10 Australian hospitals were examined blinded to trial treatment allocation. The primary endpoint was the incidence of atelectasis, defined as lung atelectasis or collapse reported on chest radiology. Pneumonia, as a secondary endpoint, required a diagnostic chest radiology report with fever, leukocytosis, or positive sputum culture. Comparison of the nitrous oxide and nitrous oxide–free groups was done according to intention to treat using chi-square tests. Results: Data from 2,328 randomized patients were included in the final data set. The two treatment groups were similar in surgical type and duration, risk factors, and perioperative management recorded for ENIGMA II. There was a 19.3% lower incidence of atelectasis with nitrous oxide (171 of 1,169 [14.6%] vs. 210 of 1,159 [18.1%]; odds ratio, 0.77; 95% CI, 0.62 to 0.97; P = 0.023). There was no difference in pneumonia incidence (60 of 1,169 [5.1%] vs. 52 of 1159 [4.5%]; odds ratio, 1.15; 95% CI, 0.77 to 1.72; P = 0.467) or combined pulmonary complications (odds ratio, 0.84; 95% CI, 0.69 to 1.03; P = 0.093). Conclusions: In contrast to the earlier ENIGMA trial, nitrous oxide anesthesia in the ENIGMA II trial was associated with a lower incidence of lung atelectasis, but not pneumonia, after major surgery. This study reanalyzed the ENIGMA II data from 10 Australian centers (approximately 33% of the total multinational cohort) to compare the incidence of atelectasis in the two treatment groups. In contrast to the original ENIGMA trial, there was a lower incidence of atelectasis with use of nitrous oxide. There was no effect of nitrous oxide on the secondary outcomes of pneumonia, combined pulmonary complications, or hospital length of stay.
What Do Social Media Influencers Say About Birth Control? A Content Analysis of YouTube Vlogs About Birth Control

ABSTRACT Youth get their sexual health information from social media, often from social media influencers (SMIs) or microcelebrities with large followings. Previous research suggests that SMIs have powerful persuasive effects on attitudes and behaviors. Thus, it is important to examine the ways in which sexual health information, such as birth control, is conveyed by SMIs. Using framing theory as a theoretical framework, this study examines characteristics of SMIs and their shared experiences pertaining to birth control. A content analysis of YouTube vlogs (n = 50) posted from December 2019–2021 was conducted on SMIs who talk about their experiences using hormonal and non-hormonal birth control. SMI status was determined based on the number of people subscribed to the YouTube channels. Results suggest that SMI YouTube videos are primarily about the discontinuation of hormonal birth control and may provide inaccurate sexual health information. Reasons for discontinuation of hormonal birth control provided by the SMIs are discussed. Future research should explore the effects of influencer sexual health messaging on beliefs, attitudes, and behaviors.
In silico prediction of the possible antidiabetic and anti-inflammatory targets of Nymphaea lotus-derived phytochemicals and mechanistic insights by molecular dynamics simulations

Abstract Nymphaea lotus is used traditionally for the treatment of diabetes and its complications. However, the mode of action and the likely bioactive phytochemicals involved are not yet fully explored. GC-MS analysis was employed to identify the inherent compounds in N. lotus leaves. To gain an insight into the antidiabetic mode of action of this plant, the identified phytochemicals were subjected to computational studies against four molecular targets of diabetes, dipeptidyl peptidase-4, glycogen synthase kinase 3, NADPH oxidase (NOX), sodium-glucose co-transporter-2, and one target of inflammation, cyclooxygenase-2. Compounds with notable binding affinity were subjected to druggability test. Results from molecular docking showed that seven of the compounds investigated exhibited druggability properties and had outstanding binding affinity values for these targets relative to values obtained for the respective standards of each of the targets. Analysis of the MD trajectories from a 100 ns atomistic run shows that the integrities of the complex systems were more stable and preserved throughout the simulation than the unbound protein. These results indicated that the antidiabetic and anti-inflammatory effects of these compounds might be via the inhibition of these targets, laying the foundation for further studies, such as in vitro and in vivo studies to fully validate the anti-diabetic agents from this plant. Communicated by Ramaswamy H. Sarma
Development and Validation of a Simulation Model for Treatment to Maintain Remission in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Fixed and tailored rituximab retreatment strategies to maintain remission in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) are associated with tradeoffs. The current study was undertaken to develop a simulation model (AAV‐Sim) to project clinical outcomes with these strategies.
Doxycycline Promotes Graft Healing and Attenuates Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Reconstruction in a Rat Model

Background: Doxycycline (Doxy) has been shown to facilitate tendon healing by reducing on-site matrix metalloproteinase (MMP) activity, but its effect on graft healing after anterior cruciate ligament reconstruction (ACLR) has not been investigated, and the therapeutic effect of Doxy in preventing ACLR-induced posttraumatic osteoarthritis (PTOA) is unclear. Hypothesis: Doxy promotes graft healing and alleviates the progression of PTOA after ACLR. Study Design: Controlled laboratory study. Methods: Sprague Dawley rats (n = 74; age, 12-13 weeks; male) that underwent ACLR were divided into untreated control and Doxy treatment (50 mg/kg/d orally until sacrifice) groups. At 2 and 6 weeks after surgery, graft healing was assessed by biomechanical testing, histology, immunohistochemical staining, and micro–computed tomography (μCT). The progression of PTOA was evaluated at 6 weeks by histology, the Mankin score, and immunofluorescence staining of the tibial plateau, and osteophyte formation was evaluated by μCT. Hindlimb weight distribution was evaluated at 6 weeks, and gait patterns were evaluated at 2 and 6 weeks. Intra-articular MMP activity was evaluated at 6 weeks in vivo using an MMP-activatable near-infrared fluorescent probe. Results: Graft healing was enhanced by Doxy treatment, and the ultimate failure load (P = .002) and stiffness of the graft (P = .007) were significantly higher in the Doxy group at week 2. Bone mineral density and bone volume/total volume for both the tibial and the femoral tunnels at week 6 in the Doxy group were significantly higher compared with in the control group (P < .05). The overall graft healing scores were significantly higher in the Doxy group. Doxy treatment enhanced graft integration, intratunnel graft integrity, and collagen birefringence; more collagen types 1 and 10 and less MMP-13 were found at the graft-bone interface. At week 6, the Doxy group had a lower modified Mankin score (P = .033) and showed fewer MMP 13–positive chondrocytes at the articular cartilage surface (P = .002), indicating moderate joint cartilage damage. μCT revealed less osteophyte formation, and gait analysis revealed more symmetric weightbearing and gait patterns, after Doxy treatment at week 6 (P < .05). In vivo imaging with the near-infrared fluorescent probe identified significantly lower intra-articular MMP activity in the Doxy group at week 6 (P = .016). Conclusion: The oral administration of Doxy was able to synchronously promote graft healing and attenuate PTOA in an ACLR rat model. Clinical Relevance: Our results indicated that Doxy, a widely used drug, is potentially beneficial to patients after ACLR.
Reliability and validity of the function in sitting test among non-ambulatory individuals with spinal cord injury

Context: Trunk impairment among non-ambulatory individuals with spinal cord injury (SCI) reduces the ability to maintain a functional sitting position and perform activities of daily living. Measuring functional sitting balance is complex and difficult in a clinical setting. The function in sitting test (FIST) is a clinical measure that includes the assessment of all the components of sitting balance. The purpose of this study is to assess the reliability and validity of the 14-item FIST among non-ambulatory individuals with SCI. Participants: Twenty-six individuals with chronic SCI. Outcome measures: Participants were evaluated with the FIST, the modified Functional Reach Test (lateral and forward mFRT) and a posturography assessment (virtual time to contact – VTC). The FIST was re-assessed during a second study visit 12 weeks later. Test-retest reliability was evaluated using intraclass coefficient correlation (ICC), the minimal detectable change (MDC) was calculated and the internal consistency reliability was assessed using Cronbach's coefficient-α. Concurrent validity of the FIST was also tested with the mFRT and the VTC. Results: Test-retest reliability was found to be excellent (ICC = 0.95) with a MDC of 4. The internal consistency was satisfactory (0.81). Moreover, the FIST correlates with the lateral mFRT (r = 0.64, P = 0.001) but not with the forward mFRT and the VTC. Conclusion: These observations provide evidence that the FIST is a reliable clinical measure with partially established validity for non-ambulatory individuals with SCI. Further studies are needed to strengthen the validity of the FIST and explore this measure in a larger sample.
Double inflation - A possible resolution of the large-scale structure problem

A model is presented for the large-scale structure of the universe in which two successive inflationary phases resulted in large small-scale and small large-scale density fluctuations. This bimodal density fluctuation spectrum in an . cap omega. = 1 universe dominated by hot dark matter leads to large-scale structure of the galaxy distribution that is consistent with recent observational results. In particular, large, nearly empty voids and significant large-scale peculiar velocity fields are produced over scales of approx.100 Mpc, while the small-scale structure over less than or equal to 10 Mpc resembles that in a low density universe, as observed. Detailed analytical calculations and numerical simulations are given of the spatial and velocity correlations. 38 refs., 6 figs.
Developing a new scoring method to evaluate human decomposition in a humid, continental (Dfb) climate in Quebec

The published literature shows a lack of methods to evaluate the patterns and extent of decomposition of human remains and to estimate the post‐mortem interval (PMI) in humid, continental (Dfb) climates such as Quebec. The aim of this study was to address this gap in the current knowledge base by providing the first observations from human corpses studied under controlled conditions in Quebec. A 12‐month study was conducted at the site for Research in Experimental and Social Thanatology; the first human taphonomy facility in Canada. Six human donors with known time of death were deposited across spring (n = 1), summer (n = 3), and autumn (n = 2) 2021. The lack of suitability of the total body score method to evaluate the extent of decomposition at the facility prompted the development of a new scoring system based on the macromorphoscopic changes observed. The scoring system was applied to the donors to evaluate decomposition throughout seasons. All donors followed comparable decomposition trajectories, regardless of the season of deposition. Eighty‐five percent of taphonomic patterns appeared in the first 25 experimental days or 5000 Kelvin accumulated degree days (350 ADD). Extensive desiccation of tissues was observed at a median of 21 experimental days across donors, resulting in a plateau within decomposition with no extensive skeletonization. To the authors' knowledge, this is the first published report of experimentally observed desiccation in such a form in a Dfb climate. This study provides new data on the types of decomposition patterns to expect in forensic investigations in southern Quebec and comparable climates.
Exploring factors influencing acceptability of online capacity building platform for HIV and AIDS monitoring and evaluation in Ghana

Introduction: Ghana’s multi-sectoral approach towards the management of HIV and AIDS has resulted in many community-level activities and programs aimed at stopping HIV infections and reducing the impact of HIV and AIDS. This study seeks to investigate whether Monitoring & Evaluation (M&E) officers in Ghana will be willing to join in an electronic learning platform which is web-based as a means of building M&E capacity. Methods: 123 out of 130 participants were involved in the study. Continuous and categorical variables were analysed using means and proportions. Structural equation Modelling technique was used to determine the factors associated with acceptability/intention to use. Results: The results showed that Attitude toward usage had a positive significant influence on acceptability/intention to use (AITU). In addition, experience with online learning and Internet discussion also had a positive influence on perceived usefulness and perceived ease of use respectively. The overall model shows 71% of variation of M&E officers’ attitude toward usage on acceptability/intention to use online M&E platform as observed by the covariates in the model. Conclusions: Attitude toward usage was observed to be the strongest determinant of the AITU online HIV/AIDS M&E platform for monitoring and evaluation activities.
A New Perspective on Priors for Generalized Linear Models

Abstract This article deals with specifications of informative prior distributions for generalized linear models. Our emphasis is on specifying distributions for selected points on the regression surface; the prior distribution on regression coefficients is induced from this specification. We believe that it is inherently easier to think about conditional means of observables given the regression variables than it is to think about model-dependent regression coefficients. Previous use of conditional means priors seems to be restricted to logistic regression with one predictor variable and to normal theory regression. We expand on the idea of conditional means priors and extend these to arbitrary generalized linear models. We also consider data augmentation priors where the prior is of the same form as the likelihood. We show that data augmentation priors are special cases of conditional means priors. With current Monte Carlo methodology, such as importance sampling and Gibbs sampling, our priors result in.