Miracle-dz/UniFAR-FTUs huggingface dataset:
Optical to microwave clock frequency ratios with a nearly continuous strontium optical lattice clock

Optical lattice clocks are at the forefront of frequency metrology. Both the instability and systematic uncertainty of these clocks have been reported to be two orders of magnitude smaller than the best microwave clocks. For this reason, a redefinition of the SI second based on optical clocks seems possible in the near future. However, the operation of optical lattice clocks has not yet reached the reliability that microwave clocks have achieved so far. In this paper, we report on the operation of a strontium optical lattice clock that spans several weeks, with more than 80% uptime. We make use of this long integration time to demonstrate a reproducible measurement of frequency ratios between the strontium clock transition and microwave Cs primary and Rb secondary frequency standards.
Exploring the opportunities and challenges to implementing interprofessional education in Saudi Arabia: a qualitative study among faculty

ABSTRACT Interprofessional education (IPE) has potential benefits for improving the quality of patient care, but its implementation is challenged with multiple barriers. The primary objectives of this study were to explore the challenges, benefits, and incentives to establishing IPE from the perspective of healthcare faculty at King Saud University. Forty-five faculty members attended six focus groups, each consisting of 6–8 faculty members representing the five colleges. The focus group interview guide included the benefits of and barriers to establishing IPE in this academic institution, curricular design, and the feasibility of support from the colleges and University administration. A SWOC (Strengths, Weaknesses, Opportunities, Challenges) frame work was utilized to guide the focus group discussions, and the data were analyzed inductively using thematic analysis. Three main themes emerged and were related to (i) barriers, (ii) benefits, (iii) opportunities to facilitate the introduction of IPE, and (iv) suggestions on how to implement IPE and overcome challenges to establish an IPE curriculum. Participants were generally supportive of IPE and aware of the constraints that might impede its implementation. Moreover, they identified potential barriers and incentives to promote IPE. Although participants appreciated the long-term benefits of IPE, creating a supportive environment will require the involvement of the academic community, including students, faculty members, and the University’s top management.
Age-associated changes in cumulus cells and follicular fluid: the local oocyte microenvironment as a determinant of gamete quality

Abstract The ovary is the first organ to age in humans with functional decline evident already in women in their early 30s. Reproductive aging is characterized by a decrease in oocyte quantity and quality, which is associated with an increase in infertility, spontaneous abortions, and birth defects. Reproductive aging also has implications for overall health due to decreased endocrinological output. Understanding the mechanisms underlying reproductive aging has significant societal implications as women globally are delaying childbearing and medical interventions have greatly increased the interval between menopause and total lifespan. Age-related changes inherent to the female gamete are well-characterized and include defects in chromosome and mitochondria structure, function, and regulation. More recently, it has been appreciated that the extra-follicular ovarian environment may have important direct or indirect impacts on the developing gamete, and age-dependent changes include increased fibrosis, inflammation, stiffness, and oxidative damage. The cumulus cells and follicular fluid that directly surround the oocyte during its final growth phase within the antral follicle represent additional critical local microenvironments. Here we systematically review the literature and evaluate the studies that investigated the age-related changes in cumulus cells and follicular fluid. Our findings demonstrate unique genetic, epigenetic, transcriptomic, and proteomic changes with associated metabolomic alterations, redox status imbalance, and increased apoptosis in the local oocyte microenvironment. We propose a model of how these changes interact, which may explain the rapid decline in gamete quality with age. We also review the limitations of published studies and highlight future research frontiers. Summary Sentence Aging is associated with genetic, epigenetic, transcriptomic, proteomic, metabolomic, and redox status changes in the local oocyte microenvironment: cumulus cells and follicular fluid.
Bone Microarchitecture in Transgender Adults: A Cross‐Sectional Study

Gender‐affirming hormone therapy aligns physical characteristics with an individual's gender identity, but sex hormones regulate bone remodeling and influence bone morphology. We hypothesized that trans men receiving testosterone have compromised bone morphology because of suppression of ovarian estradiol production, whereas trans women receiving estradiol, with or without anti‐androgen therapy, have preserved bone microarchitecture. We compared distal radial and tibial microarchitecture using high‐resolution peripheral quantitative computed tomography images in a cross‐sectional study of 41 trans men with 71 cis female controls, and 40 trans women with 51 cis male controls. Between‐group differences were expressed as standardized deviations (SD) from the mean in age‐matched cisgender controls with 98% confidence intervals adjusted for cross‐sectional area (CSA) and multiple comparisons. Relative to cis women, trans men had 0.63 SD higher total volumetric bone mineral density (vBMD; both p = 0.01). Cortical vBMD and cortical porosity did not differ, but cortices were 1.11 SD thicker (p < 0.01). Trabeculae were 0.38 SD thicker (p = 0.05) but otherwise no different. Compared with cis men, trans women had 0.68 SD lower total vBMD (p = 0.01). Cortical vBMD was 0.70 SD lower (p < 0.01), cortical thickness was 0.51 SD lower (p = 0.04), and cortical porosity was 0.70 SD higher (p < 0.01). Trabecular bone volume (BV/TV) was 0.77 SD lower (p < 0.01), with 0.57 SD fewer (p < 0.01) and 0.30 SD thicker trabeculae (p = 0.02). There was 0.56 SD greater trabecular separation (p = 0.01). Findings at the distal radius were similar. Contrary to each hypothesis, bone microarchitecture was not compromised in trans men, perhaps because aromatization of administered testosterone prevented bone loss. Trans women had deteriorated bone microarchitecture either because of deficits in microstructure before treatment or because the estradiol dosage was insufficient to offset reduced aromatizable testosterone. Prospective studies are needed to confirm these findings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Prevalence and predictors of team-based care activities between primary care providers and embedded behavioral health providers: a national survey

ABSTRACT Primary care (PC) settings increasingly use team-based care activities with embedded behavioral health providers (BHPs) to enhance patient care via group medical visits, conjoint appointments, team huddles, and warm handoffs. Aim 1 was to describe the variation of team-based care activities within integrated PC clinics. Aim 2 was to explore whether factors associated with the BHP (e.g., gender, training, and experience) and the PC setting (e.g., perceived teamwork) predict engagement in team-based activities. A national sample of eligible BHPs (n = 345; 14.2% response rate) completed an anonymous survey assessing the presence/intensity of team-based care activities. 90% of BHPs reported regularly engaging in team-based care activities with PC teams. Most engagement occurred when providing feedback to PC providers (90.4% at least daily) and during warm handoffs (90.4% at least once daily). Engagement in team-based care was predicted by the level of teamwork occurring within the PC clinic (βs = .41-.47; ps < .001) and BHP characteristics, such as the number of years spent in PC (βs = .24-.26, ps < .001). Although these data are promising, with many BHPs reportedly engaging in team-based activities with PC teams, there is significant variation. Researchers should continue to explore whether the engagement in these team-based care activities enhances patient care.
Human Milk SARS-CoV-2 Antibodies up to 6 Months After Vaccination.

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies have been detected in human milk up to 6 weeks post-coronavirus disease 2019 (COVID-19) vaccination. We evaluated SARS-CoV-2-specific antibodies, neutralization activity, effect of pasteurization, and persistence through 6 months after vaccination. METHODS This prospective longitudinal study enrolled 30 pregnant or lactating women. SARS-CoV-2 antibodies and neutralization capacity were analyzed using an enzyme-linked immunosorbent assay compared at prevaccination and 1, 3, and 6 months postvaccination, and through Holder pasteurization. RESULTS Human milk SARS-CoV-2-specific IgG levels peaked at 1 month postvaccination and persisted above prevaccination levels for at least 6 months (P = .005). SARS-CoV-2-specific IgA was detected at 1 and 3 months (both P < .001) but waned by 6 months compared with baseline (P = .07). Milk SARS-CoV-2-specific IgG and IgA correlated with serum IgG at the same time point (R2 = 0.37, P < .001 and R2 = 0.19, P < .001). Neutralization activity was seen in 83.3%, 70.4%, and 25.0% of milk samples at 1, 3, and 6 months postvaccination. Neutralization most strongly correlated with SARS-CoV-2-specific IgG (R2 = 0.57, P < .001). Pre- and postpasteurization samples showed similar IgG (0.84 vs 1.07, P = .36) and neutralizing activity (57.7% vs 58.7% inhibition, P = .27), but lower IgM and IgA levels postpasteurization (0.09 vs 0.06, P = .004 and 0.21 vs 0.18, P = .043). CONCLUSIONS The data suggest that human milk SARS-CoV-2-specific antibodies may be available to milk-fed infants for up to 6 months. In addition, donor milk from vaccinated mothers retain IgG and neutralizing activity.
The impact of stay-at-home orders on vulnerability assessments and precautionary intentions during a pandemic

ABSTRACT In 2020, a novel emerging infectious disease – COVID-19 – became a global pandemic and prompted unprecedented social distancing measures. We examined the associations of voluntary stay-at-home (SAH) orders during the COVID-19 pandemic with vulnerability assessments and precautionary intentions (e.g. social distancing, hand washing). A quasi-experimental study using an online adult sample was conducted in U.S. states with and without voluntary SAH orders during the COVID-19 pandemic. Self-report surveys assessed vulnerability assessments and precautionary intentions. Participants living in states with SAH orders showed inflated vulnerability assessments for contracting COVID-19, and this association was stronger for affect-laden than cognitively-based assessments. Moreover, only affect-laden vulnerability assessments were uniquely associated with precautionary intentions and accounted for the relationship between SAH orders and precautionary intentions. Our study was among the first to explore the impact of voluntary SAH orders on vulnerability assessments and precautionary intentions. Results are discussed in terms of their implications for health behavioral models and applications for promoting self-protective actions during a pandemic.
The possible protective role of N-acetyl cysteine on duodenal mucosa of high fat diet and orlistat treated adult male albino rats and the active role of tumor necrosis factor α (TNFα) and Interleukin 6 (IL6) (histological and biochemical study)

ABSTRACT Background Obesity is a major universal health issue linked to a majority of illness. Aim To evaluate the histological and biochemical changes occurred in the duodenal mucosa of high fat diet HFD and orlistat fed rats and to assess the possible protective role of N-acetyl cysteine NAC supplementation. Material and method Sixty male albino rats weighing 180–200 g were classified randomly into control group I and three experimental groups (HFD group II, HFD + orlistat group III, and HFD + orlistat + NAC group IV). All experimental groups received HFD alone/and treatment for 6 weeks. Group III received orlistat (32 mg/kg/day) before meals and group IV received the same regimen as group III in addition to NAC (230 mg/kg/day) after meals. After completion of the experiment, duodenal sections were processed for histological examination, oxidative stress parameters, and semiqualitative real time PCR for proinflammatory mediators TNFα and IL6 evaluation. Also, plasma lipid parameters were assessed and morphometric duodenal results were analyzed statistically. Results By histological examination of HFD and (HFD + orlistat) groups, we found severe to moderate duodenal structural disturbances, increased goblet cells, collagen fibers, and BAX and iNOS immunostaining. By Biochemical examination, both groups showed increased proinflammatory markers level (TNFα and IL6) with decreased all antioxidant parameters and increased MDA. Moreover, NAC treatment in group IV significantly reduced all structural changes, levels of proinflammatory mediators and increased all antioxidant parameter levels and decreased MDA. Conclusion All findings elucidated that NAC could be accounted to be a useful drug for protection of duodenal mucosa of HFD and orlistat treated animals.
Transcription factor BES1 interacts with HSFA1 to promote heat stress resistance of plants

Heat stress is a major environmental stress type that can limit plant growth and development. To survive sudden temperature increases, plants utilize the heat shock response, an ancient signaling pathway. Initial results had suggested a role for brassinosteroids (BRs) in this response. Brassinosteroids are growth‐promoting steroid hormones whose activity is mediated by transcription factors of the BES1/BZR1 subfamily. Here, we provide evidence that BES1 can contribute to heat stress signaling. In response to heat, BES1 is activated even in the absence of BRs and directly binds to heat shock elements (HSEs), known binding sites of heat shock transcription factors (HSFs). HSFs of the HSFA1 type can interact with BES1 and facilitate its activity in HSE binding. These findings lead us to propose an extended model of the heat stress response in plants, in which the recruitment of BES1 is a means of heat stress signaling cross‐talk with a central growth regulatory pathway.
The absence of genotoxicity of a mixture of aloin A and B and a commercial aloe gel beverage

Abstract Aloe products are increasingly valued as ingredients in food supplements and as flavoring agents. The global Aloe vera market is varied, large, growing, and increasingly important in food, cosmetics, and medicines. Aloin, an anthraquinone glycoside, is one of the major components by weight of the anthraquinone derivatives of Aloe vera gel. Principal metabolites, aloe emodin and emodin, are a source of debate concerning toxic vs salutary effects, hence the accurate toxicological characterization of these compounds has become increasingly important. The purpose of this study was to determine the genotoxic profile of a stabilized Aloe vera juice product derived from the inner filet and marketed as a beverage currently sold in the European Union containing 8 to 10 ppm aloin and a mixture of purified aloin A and B. The present data confirm that a commercial stabilized Aloe vera gel intended for consumption as a juice beverage is not genotoxic. Furthermore, both aloin A and B were negative in the same assays and therefore are also not genotoxic. These results are consistent with the work of other groups and contrast with data obtained using products containing the Aloe vera latex hydroxyanthracene derivatives (HADs).
Axonal Protection by Netarsudil, a ROCK Inhibitor, Is Linked to an AMPK-Autophagy Pathway in TNF-Induced Optic Nerve Degeneration

Purpose Netarsudil, a Rho kinase inhibitor with norepinephrine transport inhibitory effect, lowers intraocular pressure, however, its effect on axon damage remains to be elucidated. The aim of the current study was to investigate the effect of netarsudil on TNF-induced axon loss and to examine whether it affects phosphorylated-AMP-activated kinase (p-AMPK) and autophagy in the optic nerve. Methods Intravitreal administration of TNF or TNF with netarsudil was carried out on rats and quantification of axon number was determined. Electron microscopy determined autophagosome numbers. Localization of p-AMPK expression was examined by immunohistochemistry. The changes in p62, LC3-II, and p-AMPK levels were estimated in the optic nerve by immunoblot analysis. The effect of an AMPK activator A769662 or an AMPK inhibitor dorsomorphin on axon number was evaluated. Results Morphometric analysis revealed apparent protection by netarsudil against TNF-induced axon degeneration. Netarsudil increased autophagosome numbers inside axons. Netarsudil treatment significantly upregulated optic nerve LC3-II levels in both the TNF-treated eyes and the control eyes. Increased p62 protein level induced by TNF was significantly ameliorated by netarsudil. The netarsudil administration alone lessened p62 levels. Netarsudil significantly upregulated the optic nerve p-AMPK levels. A769662 exhibited obvious axonal protection against TNF-induced damage. A769662 treatment upregulated LC3-II levels and the increment of p62 level induced by TNF was significantly ameliorated by A769662. Immunohistochemical analysis revealed that p-AMPK is present in axons. Netarsudil-mediated axonal protection was significantly suppressed by dorsomorphin administration. Conclusions Netarsudil upregulated p-AMPK and autophagy. Netarsudil-mediated axonal protection may be associated with upregulated p-AMPK.
Effectiveness and adverse effects of anakinra in treatment of rheumatoid arthritis: a systematic review.

OBJECTIVE Rheumatoid arthritis (RA) can be described as a chronic, inflammatory, progressive, autoimmune disorder characterized by generalized inflammation of the synovial joints, which hereby triggers the progressive erosion of both cartilage and bone. Anakinra is a recombinant form of human IL-1 receptor antagonist which targets the type I IL-1 receptor. In the present systematic review, we intend to evaluate the effectiveness and adverse effects of interleukin-1 antagonists in the treatment of rheumatoid arthritis. MATERIALS AND METHODS The database search was carried out using PubMed (Medline), Web of Science (Clarivate), Embase, Scopus, and Cochrane Library for the existing studies. A total of 3912 relevant articles were identified as per the search strategy. Out of them, 854 duplicate records and further 3024 records were excluded after going through their titles and abstracts. Further, out of 42 articles left, we excluded 32 more articles matching our inclusion criteria and excluding the reviews and case studies. Finally, we included 10 relevant studies that focused on both the effectiveness and adverse effects of interleukin-1 antagonists during the treatment of adult patients with rheumatoid arthritis in the present analysis. Nine out of 10 included studies are randomized trials (RCT) except for 1 study, which was an extension study. RESULTS The results showed an ACR20 response at week 12 and were the most common primary outcome measure in the present review. Various secondary outcome measures studied were changed from baseline at week 24 in individual ACR components. ACR50 and ACR70 responses at subsequent weeks (12 and 24), ESR components, HAQ score, CRP levels, and ESR. Notably, more improvement was observed with anakinra in comparison to placebo for achieving ACR50 and ACR70 responses at 24 weeks. Premature withdrawal of participants was observed in almost all the studies. Adverse drug reactions were attributed to be the most common reason followed by loss of efficacy for withdrawal of patients from the treatment. The infectious episode was another common adverse effect observed in both anakinra and placebo groups. Some malignancies were also documented in the included researches of this systematic analysis. We observed a lower overall incidence of malignancies for the studies screened compared with that of the general population. CONCLUSIONS This review demonstrated that anakinra is safe, effective, and well-tolerated, with no significant difference in adverse effects compared to placebo in rheumatoid arthritis patients.
Clinical applications of personalising the neural components of visual image quality metrics for individual eyes

Eyecare is evolving increasingly personalised corrections and increasingly personalised evaluations of corrections on‐eye. This report describes individualising optical and neural components of the VSX (visual Strehl) metric and evaluates personalisation using two clinical applications. (1) Better understanding visual experience: While VSX tracks visual performance in typical eyes, non‐individualised metrics underestimated visual performance in highly aberrated eyes – could this be understood by personalising metrics? (2) Metric‐optimised objective spherocylindrical refractions in typical and atypical eyes have used neural weighting functions of typical eyes – will personalisation affect the outcome in clinical 0.25D steps?
Montelukast and neuropsychiatric events – a sequence symmetry analysis

Abstract Objectives Neuropsychiatric events (NEs) reported with montelukast during post-marketing surveillance by the US Food & Drug Administration resulted in a 2008 safety alert and a black box warning in 2020. Our objective was to evaluate montelukast exposure and NEs risk using sequence symmetry analysis. Methods National Veterans Health Administration (VHA) administrative data were used to identify 11 840 patients prescribed incident montelukast during fiscal year 2014. Incident prescribing of neuropsychiatric medication was used as a proxy marker for incident NEs and included antidepressants, benzodiazepines, hypnotics, antipsychotics, mood stabilizers, and buspirone. Symmetry ratios were calculated as the ratio of patients with an incident neuropsychiatric event in the year following montelukast initiation to the year preceding initiation. Exposure counterfactual analyses were used to examine the relationship between potential therapeutic alternatives to montelukast and risk for NEs. Results Incident NEs were observed in 2305 patients following montelukast initiation and 2734 patients preceding montelukast initiation (SR 0.84, 95% CI 0.80–0.89). Sensitivity analyses examining each of the 6 sub-types of psychiatric medications also failed to show increased risk of NEs following montelukast initiation. Therapeutic alternatives to montelukast, such as inhaled corticosteroids, were also not associated increased NE risk. Conclusions Initiation of montelukast was not associated with increased risk of a variety of NEs in this sequence symmetry analysis involving adult patients in the VHA. Our findings do not support the hypothesis that NEs are associated with montelukast initiation.
Changes in eicosapentaenoic acid and docosahexaenoic acid and risk of cardiovascular events and atrial fibrillation: A secondary analysis of the OMEMI trial

The cardiovascular benefit from n‐3 polyunsaturated fatty acids (PUFAs) after acute myocardial infarction (AMI) is controversial, and the importance of serum eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations for clinical events is unclear.