Miracle-dz/UniFAR-FTUs huggingface dataset:
Barriers, Enablers, and Consumer Design Ideas for Health Literacy Responsive Hospital Waiting Areas: A Framework Method Analysis

Aim: The study aim was to (1) investigate the barriers and enablers experienced by consumers to accessing and engaging with health tools in hospital waiting areas and (2) evaluate consumers’ ideas for designing a health literacy responsive waiting area. Background: Health information, resources, and supports (“health tools”) in waiting areas should be responsive to the health literacy needs of consumers. However, consumers’ experiences of using health tools and their ideas for improving them are not known. Methods: Multicenter study was set in hospital waiting areas of outpatient rehabilitation services. Semistructured in-person interviews were conducted with 33 adult consumers attending appointments for various health conditions. Seven stages of the Framework Method were used to analyze data. Results: Six themes were identified which explained barriers and enablers from the perspective of consumers. The barriers were accessibility issues; personal factors—physical condition, emotional state, and preferences; and poorly presented and outdated resources. The enablers were design suits consumer needs and preferences; usable in available time or portable; and compatible environment for engaging and sharing. Consumers shared design ideas which fit within four typologies. Conclusions: A range of barriers and enablers exist which have an impact on consumers’ ability to engage with available health information, resources, and supports in hospital outpatient waiting areas. Practical insights from the perspective of consumers can be applied to future health service design. Consumer’s design ideas suggest that partnerships with consumers should be formed to design health literacy responsive waiting areas.
Six-Month In Vivo Safety Profiling of Topical Ocular AVV5–Decorin Gene Transfer

Purpose A significant remission of corneal fibrosis and neovascularization in rabbit eye in vivo was observed from a tissue-selective localized adeno-associated virus (AAV)5–Decorin (Dcn) gene therapy. This study sought to investigate 6-month toxicity profiling of this gene therapy for the eye in vivo using a rabbit model. Methods A small epithelial scrape followed by corneal drying was performed unilaterally in 12 rabbit eyes and either AAV5–Dcn (n = 6) or naked vector (n = 6) was delivered topically using a cloning cylinder technique. Contralateral eyes served as naïve control (n = 6). Safety and tolerability measurements in live rabbits were performed periodically until month 6 using multimodel clinical ophthalmic imaging tools—a slit lamp, stereomicroscope, and HRT3-RCM in vivo confocal microscope. Thereafter, corneas were excised and subjected to hematoxylin and eosin staining, Mason trichome staining, propidium iodide nuclear staining, and quantitative real-time polymerase chain reaction analyses. Results Clinical eye examinations based on the modified Hackett–McDonald ocular scoring system, and in vivo confocal imaging of the cornea showed no signs of ocular toxicity in rabbit eyes given AAV5–Dcn gene transfer vs control eyes (P > 0.05) through 6 months after treatment. The histologic and molecular analyses showed no significant differences in AAV5–Dcn vs AAV naked or naïve control groups (P > 0.05) and were in accordance with the masked clinical ophthalmic observations showing no abnormalities. Conclusions Topical tissue-targeted localized AAV5–Dcn gene therapy seems to be safe and nontoxic to the rabbit eye in vivo. Translational Relevance AAV5–Dcn gene therapy has the potential to treat corneal fibrosis and neovascularization in vivo safely without significant ocular toxicity.
Impact of Clomiphene Citrate on the Steroid Profile in Dysmetabolic Men with Low Testosterone Levels

Abstract Clomiphene citrate (CC) in male hypogonadism increases testosterone (T) and estrogen levels by stimulating pituitary gonadotropin release. Our group confirmed these hormonal changes in a randomized, cross-over, double-blind trial of CC versus placebo in addition to metformin, conducted in 21 obese dysmetabolic men with low T levels. However, we hypothesize that based on its mechanism of action, CC may directly or indirectly affect adrenal steroidogenesis. The aim of this sub-study was to better understand the changes in steroid levels and metabolism induced by CC treatment. We assessed 17α-hydroxypregnelone (17αOH-P5), dehydroepiandrosterone (DHEA), progesterone (P4), 17α-hydroxyprogesterone (17αOH-P4), androstenedione (A), T, dihydrotestosterone (DHT), estrone (E1), 17β-estradiol (E2), 11-deoxycortisol (11 S), cortisol (F), and cortisone (E) by LC-MS/MS, and corticosteroid binding globulin (CBG) by ELISA, before and after each treatment. In addition, free-F and steroid product/precursor ratios were calculated. We observed a significant change in serum levels induced by CC compared with placebo for 17αOH-P4, DHT, T, E2, E1, F, E, and CBG, but not free-F. In addition, compared to placebo, CC induced higher 17αOH-P4/P4, E2/E1, 17αOH-P4/17αOH-P5, A/17αOH-P4, T/A, E1/A, F/11 S, and F/E ratios. Therefore, besides the CC stimulating effect on testis steroidogenesis, our study showed increased F, E, but not free-F, levels, indicating changes in steroid metabolism rather than adrenal secretion stimulation. The steroid profiling also revealed the CC stimulation of the Δ5 rather than the Δ4 pathway, thus indicating considerable testicular involvement in the increased androgen secretion.
Cross-Site Severity Assessment of COVID-19 From CT Images via Domain Adaptation

Early and accurate severity assessment of Coronavirus disease 2019 (COVID-19) based on computed tomography (CT) images offers a great help to the estimation of intensive care unit event and the clinical decision of treatment planning. To augment the labeled data and improve the generalization ability of the classification model, it is necessary to aggregate data from multiple sites. This task faces several challenges including class imbalance between mild and severe infections, domain distribution discrepancy between sites, and presence of heterogeneous features. In this paper, we propose a novel domain adaptation (DA) method with two components to address these problems. The first component is a stochastic class-balanced boosting sampling strategy that overcomes the imbalanced learning problem and improves the classification performance on poorly-predicted classes. The second component is a representation learning that guarantees three properties: 1) domain-transferability by prototype triplet loss, 2) discriminant by conditional maximum mean discrepancy loss, and 3) completeness by multi-view reconstruction loss. Particularly, we propose a domain translator and align the heterogeneous data to the estimated class prototypes (i.e., class centers) in a hyper-sphere manifold. Experiments on cross-site severity assessment of COVID-19 from CT images show that the proposed method can effectively tackle the imbalanced learning problem and outperform recent DA approaches.
Development and Validation of Bioanalytical Method for Simultaneous Estimation of Nebivolol Enantiomers in Human Plasma Using Liquid Chromatography-tandem Mass Spectrometry

The present study describes a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of S-RRR and R-SSS nebivolol (nebivolol enantiomers) in human plasma using solid phase extraction technique. Method of both S-RRR and R-SSS nebivolol (nebivolol enantiomers) has been developed and validated using racemic nebivolol D4 as an internal standard. Analytes from human plasma were extracted by ion exchange cartridges and subsequently separated on chiral column using acetonitrile: ammonium carbonate in water, 158 mg/L 80:20% v/v as a mobile phase, at a flow rate of 0.9 mL/min. Quantification of S-RRR and R-SSS nebivolol and R-nebivolol D4 was performed using multi-reaction monitoring mode (MRM) in positive mode. The calibration curve was linear (r2 > 0.99) over the concentration range of 20.0 to 6000 pg/mL for S-RRR and R-SSS nebivolol. The intra-day and inter-day assay precision revealed within ±15% (at LLOQ level ±20%) with accuracy within 85%-115% (at LLOQ level 80% -120%). The LC-MS/MS method was fully validated for all the validation parameters as per current regulatory requirement (US FDA, EU) such as selectivity, matrix effect, recovery and stability (in solution and in matrix stability).
Melatonin exerts neuroprotection in a chronodisrupted rat model through reduction in oxidative stress and modulation of autophagy

ABSTRACT Circadian disruption due to artificial light affects cellular redox homeostasis and may lead to neurodegenerative diseases. The aim of the present study was to investigate the effect of continuous light exposure (CLE) and continuous dark exposure (CDE) along with melatonin supplementation on neuronal redox status, mitochondrial complexes, membrane bound transporters, inflammation, autophagy and neurodegeneration in chronodisrupted model of rat. In the study artificial light of white LED bulb with 500 lux intensity was used. Melatonin (10 mg/kg b.w., orally) was supplemented to control and CLE groups for 10 days. Standard protocols were employed to measure pro-oxidants, non-enzymatic antioxidants, and mitochondrial complexes in brain tissues. Membrane-bound ion transporter activities were evaluated in the crude synaptosomes. Gene expression analysis was performed to assess the expression of inflammatory, autophagy and neuronal marker genes. Histopathological changes in cerebral cortex and different hippocampus regions of the brain were studied. Melatonin exerted a significant normalization of redox status biomarkers in brain tissue. Further melatonin restored the activities of mitochondrial complexes and synaptosomal membrane bound ion transporters. RT-PCR data revealed that melatonin downregulated the expression of inflammatory (TNF-α, IL-6) autophagy (Atg-3, Beclin-1) and neurodegenerative genes (Ngb and NSE) in CLE group. Melatonin also preserved the histology architecture in cerebral cortex and hippocampus. Our results indicate that melatonin exerts a potent neuroprotective effect through reduction of oxidative stress, inflammation and autophagy. Melatonin supplementation might be a promising neurotherapeutic in the treatment neurodegenerative disorders caused by circadian disturbances.
Protein cofactors and substrate influence Mg2+-dependent structural changes in the catalytic RNA of archaeal RNase P

Abstract The ribonucleoprotein (RNP) form of archaeal RNase P comprises one catalytic RNA and five protein cofactors. To catalyze Mg2+-dependent cleavage of the 5′ leader from pre-tRNAs, the catalytic (C) and specificity (S) domains of the RNase P RNA (RPR) cooperate to recognize different parts of the pre-tRNA. While ∼250–500 mM Mg2+ renders the archaeal RPR active without RNase P proteins (RPPs), addition of all RPPs lowers the Mg2+ requirement to ∼10–20 mM and improves the rate and fidelity of cleavage. To understand the Mg2+- and RPP-dependent structural changes that increase activity, we used pre-tRNA cleavage and ensemble FRET assays to characterize inter-domain interactions in Pyrococcus furiosus (Pfu) RPR, either alone or with RPPs ± pre-tRNA. Following splint ligation to doubly label the RPR (Cy3-RPRC domain and Cy5-RPRS domain), we used native mass spectrometry to verify the final product. We found that FRET correlates closely with activity, the Pfu RPR and RNase P holoenzyme (RPR + 5 RPPs) traverse different Mg2+-dependent paths to converge on similar functional states, and binding of the pre-tRNA by the holoenzyme influences Mg2+ cooperativity. Our findings highlight how Mg2+ and proteins in multi-subunit RNPs together favor RNA conformations in a dynamic ensemble for functional gains.
Steady-State Cortico-Cortical Evoked Potential

Purpose: The present study evaluated the utility of the steady-state responses of cortico-cortical evoked potentials (SSCCEPs) and compared them with the responses of conventional CCEPs. Methods: Eleven patients with medically intractable focal epilepsy who underwent the implantation of subdural electrodes or stereoelectroencephalography were enrolled. Conventional CCEPs were obtained by averaging responses to alternating 1-Hz electrical stimuli, and 5-Hz stimuli were delivered for recording SSCCEPs. The distribution of SSCCEPs was assessed by a frequency analysis of fast Fourier transform and compared with conventional CCEPs. Results: Steady-state responses of cortico-cortical evoked potentials were successfully recorded in areas consistent with conventional CCEPs in all patients. However, SSCCEPs were more easily disturbed by the 5-Hz stimulation, and small responses had difficulty generating SSCCEPs. Conclusions: Steady-state responses of cortico-cortical evoked potentials may be a useful alternative to conventional CCEPs.
Tyrosine phosphorylation of lamin A by Src promotes disassembly of nuclear lamina in interphase

Phosphorylation of lamin A at tyrosine residue 45 by Src has an adverse effect on the assembly of nuclear lamina, which may be involved in nuclear dysmorphia, genomic instability, and nuclear plasticity in interphase. Lamins form the nuclear lamina, which is important for nuclear structure and activity. Although posttranslational modifications, in particular serine phosphorylation, have been shown to be important for structural properties and functions of lamins, little is known about the role of tyrosine phosphorylation in this regard. In this study, we found that the constitutively active Src Y527F mutant caused the disassembly of lamin A/C. We demonstrate that Src directly phosphorylates lamin A mainly at Tyr45 both in vitro and in intact cells. The phosphomimetic Y45D mutant was diffusively distributed in the nucleoplasm and failed to assemble into the nuclear lamina. Depletion of lamin A/C in HeLa cells induced nuclear dysmorphia and genomic instability as well as increased nuclear plasticity for cell migration, all of which were partially restored by re-expression of lamin A, but further promoted by the Y45D mutant. Together, our results reveal a novel mechanism for regulating the assembly of nuclear lamina through Src and suggest that aberrant phosphorylation of lamin A by Src may contribute to nuclear dysmorphia, genomic instability, and nuclear plasticity.
A phosphate binding pocket is a key determinant of exo- versus endo-nucleolytic activity in the SNM1 nuclease family

Abstract The SNM1 nucleases which help maintain genome integrity are members of the metallo-β-lactamase (MBL) structural superfamily. Their conserved MBL-β-CASP-fold SNM1 core provides a molecular scaffold forming an active site which coordinates the metal ions required for catalysis. The features that determine SNM1 endo- versus exonuclease activity, and which control substrate selectivity and binding are poorly understood. We describe a structure of SNM1B/Apollo with two nucleotides bound to its active site, resembling the product state of its exonuclease reaction. The structure enables definition of key SNM1B residues that form contacts with DNA and identifies a 5′ phosphate binding pocket, which we demonstrate is important in catalysis and which has a key role in determining endo- versus exonucleolytic activity across the SNM1 family. We probed the capacity of SNM1B to digest past sites of common endogenous DNA lesions and find that base modifications planar to the nucleobase can be accommodated due to the open architecture of the active site, but lesions axial to the plane of the nucleobase are not well tolerated due to constriction around the altered base. We propose that SNM1B/Apollo might employ its activity to help remove common oxidative lesions from telomeres.
Pacemaker‐Based Cardiac Neuromodulation Therapy in Patients With Hypertension: A Pilot Study

Background In prior unblinded studies, cardiac neuromodulation therapy (CNT) employing a sequence of variably timed short and longer atrioventricular intervals yielded sustained reductions of systolic blood pressure (SBP) in patients with hypertension. The effects of CNT on SBP were investigated in this double‐blind randomized pilot study. Methods and Results Eligible patients had daytime ambulatory SBP (aSBP) ≥130 mm Hg and office SBP ≥140 mm Hg despite taking ≥1 antihypertensive medication, and an indication for a dual‐chamber pacemaker. Patients underwent Moderato device implantation, which was programmed as a standard pacemaker during a 1‐month run‐in phase. Patients whose daytime aSBP was ≥125 mm Hg at the end of this period were randomized (1:1, double blind) to treatment (CNT) or control (CNT inactive). The primary efficacy end point was the between‐group difference of the change in 24‐hour aSBP at 6 months. Of 68 patients initially enrolled and who underwent implantation with the Moderato system, 47 met criteria for study continuation and were randomized (26 treatment, 21 control). The mean age was 74.0±8.7 years, 64% were men, left ventricular ejection fraction was 59.2%±5.7%, and aSBP averaged 141.0±10.8 mm Hg despite the use of 3.3±1.5 antihypertensive medications; 81% had isolated systolic hypertension. Six months after randomization, aSBP was 11.1±10.5 mm Hg (95% CI, −15.2 to −8.1 mm Hg) lower than prerandomization in the treatment group compared with 3.1±9.5 mm Hg (−7.4 to 1.2 mm Hg) lower in controls, yielding a net treatment effect of 8.1±10.1 mm Hg (−14.2 to −1.9 mm Hg) (P=0.012). There were no Moderato device– or CNT‐related adverse events. Conclusions CNT significantly reduced 24‐hour aSBP in patients with hypertension with a clinical indication for a pacemaker. The majority of patients had isolated systolic hypertension, a particularly difficult group of patients to treat. Registration URL: https://www.clinicaltrials. gov; Unique identifier: NCT02837445.
Genetic Variation of Glutathione S-Transferase M1 Is Associated with Patients with Ovarian Endometriosis and Endometriosis-Related Primary Infertility

Background: The aim of the study was to investigate the role of the genetic variation of glutathione S-transferase M1 (GSTM1) in the development of ovarian endometriosis and endometriosis-related primary infertility risk. Methods: This case-control study included 564 women with ovarian endometriosis and 576 normal women in the control group in northern China. The polymorphism of GSTM1 was genotyped by polymerase chain reaction (PCR)/ligase detection reaction method. To assess the biological significance of polymorphisms, the level of GSTM1 mRNA expression in patients’ endometrial tissues with different genotypes was detected by quantitative real-time PCR (qRT-PCR). Results: Compared with the positive genotype, the null genotype of GSTM1 was associated with the risk of developing ovarian endometriosis (OR = 1.29, 95% CI = 1.02–1.62). Further analysis showed that patients with a null genotype also had a significantly higher risk of primary infertility than patients with positive genotypes (OR = 1.59, 95% CI = 1.01–2.49). In addition, we found that GSTM1 mRNA expression was present in the endometrial tissue of all patients, but the expression level of patients with a positive genotype was nearly 10 times higher than that of patients with a negative genotype. Conclusion: Our results suggest that the GSTM1 polymorphism is not only related to the genetic susceptibility to ovarian endometriosis but also a potential molecular marker of primary infertility in patients with ovarian endometriosis.
Midcareer Medical School Research Faculty Perspectives on Vitality and Professionalism During the COVID-19 Pandemic

Key Points Question How do midcareer medical school faculty perceive the impact of the COVID-19 pandemic on their lives and their work? Findings In this qualitative study of 39 midcareer research faculty, dominant themes included finding increased meaningfulness of work; a sense of professionalism and moral responsibility; enhanced relationships with colleagues; reassertion of career choice; disrupted research; impact on clinical work; attention to health disparities, social justice, and advocacy; increased family responsibilities; psychological stress; and focus on leadership. Meaning In this study of a diverse group of midcareer medical school faculty, the experience of working during the pandemic appeared to have had important positive impacts on physician investigators and PhD scientists, contributing to their vitality and professional dedication that were associated with intrinsic motivators.
When Coffee Collapsed: An Economic History of HIV in Uganda

ABSTRACT In some Ugandan fishing communities, almost half the population lives with HIV. Researchers designate these communities “HIV hotspots” and attribute disproportionate disease burdens to “sex-for-fish” relationships endemic to the lakeshores. In this article, we trace the emergence of Uganda’s HIV hotspots to structural adjustment. We show how global economic policies negotiated in the 1990s precipitated the collapse of Uganda’s coffee sector, causing mass economic dislocation among women workers, who migrated to the lake. There, they entered overt forms of sex work or marriages they may have otherwise avoided, intimate economic arrangements that helped to “engineer the spread of HIV,” as one respondent recounted.
Supramaximal Interval Running Prescription in Australian Rules Football Players: A Comparison Between Maximal Aerobic Speed, Anaerobic Speed Reserve, and the 30-15 Intermittent Fitness Test

Abstract Collison, J, Debenedictis, T, Fuller, JT, Gerschwitz, R, Ling, T, Gotch, L, Bishop, B, Sibley, L, Russell, J, Hobbs, A, and Bellenger, CR. Supramaximal interval running prescription in Australian Rules Football players: A comparison between maximal aerobic speed, anaerobic speed reserve and the 30-15 intermittent fitness test. J Strength Cond Res 36(12): 3409–3414, 2022—Accurate prescription of supramaximal interval running during Australian Rules Football (AF) preparatory periods is important to facilitate the specific targeting of physiological and neuromuscular adaptation. This study compared the variability in supramaximal interval running performance prescribed by proportion of maximal aerobic speed (MAS), anaerobic speed reserve (ASR), and 30-15 intermittent fitness test (30-15IFT) terminal speed. Seventeen male junior AF players first completed assessments of MAS, ASR, and 30-15IFT in a randomized order. They subsequently performed supramaximal interval running trials (15 seconds on: 15 seconds off until volitional exhaustion) at 120% MAS, 20% ASR, and 95% 30-15IFT in a randomized order. Variability in time to exhaustion (TTE) for each prescription method was calculated as the mean of the square root of the squared difference between the individual value and the mean value, and it was compared via repeated-measures analysis of variance with statistical significance set at p ≤ 0.05. Time to exhaustion during supramaximal interval running was not different between the prescription methods (p = 0.58). Time to exhaustion residuals were reduced when prescribed by ASR compared with MAS (standardized mean difference [SMD] = −0.47; 29%); however, confidence intervals about this reduction indicated that there was some uncertainty in this finding (SMD = −1.03 to 0.09; p = 0.09). Trivial differences in TTE residuals were present when prescribed by 30-15IFT compared with MAS (SMD = −0.05 ± 0.59; p = 0.86). Although there was some uncertainty about the reduction in supramaximal interval running performance variability when prescribed by ASR compared with MAS, the 29% reduction exceeds the inherent error in TTE efforts (i.e., ∼9–15%) and may thus be considered practically meaningful. Reducing supramaximal interval running performance variability ensures similar physiological demand across individuals, potentially facilitating similar degrees of physiological adaptation.