Miracle-dz/UniFAR-FTUs huggingface dataset:
Willingness to receive COVID-19 vaccine and associated factors among adult chronic patients. A cross-sectional study in Northwest Ethiopia

Background People with pre-existing chronic diseases are more likely to acquire COVID-19 infections, which can be fatal, and die from COVID-19 illness. COVID-19 vaccination will benefit those at a higher risk of developing complications and dying from the disease. This study aimed to determine chronic patients’ willingness to receive a COVID-19 vaccine and the factors that influence their willingness. Method An institutional-based cross-sectional study was conducted among 423 adult chronic patients in the University of Gondar specialized hospital outpatient departments. The participants were chosen using systematic random sampling methods with an interval of 5. Face-to-face interviews were used to collect data from eligible respondents. Epi-data version 4.6 and SPSS version 25 were used for the data entry data analysis. Bivariable and multivariable binary logistic regression analyses were used to evaluate the relationship between the dependent and independent factors. An odds ratio with 95 percent confidence intervals and a P-value was used to determine the association’s strength and statistical significance. Result Out of 401 respondents, 219 (54.6%) with [95% CI (49.7–59.5%)] of study participants were willing to receive the COVID-19 vaccination. Being a healthcare worker (AOR = 2.94, 95% CI: 1.24–6.96), Lost family members or friends due to COVID-19 (AOR = 2.47, 95% CI: 1.21–5.00), good knowledge about COVID-19 vaccine (AOR = 2.44, 95% CI: 1.37–4.33), favorable attitude towards COVID-19 vaccine (AOR = .8.56 95% CI: 4.76–15.38), perceived suitability of the COVID-19 infection (AOR = 2.94, 95% CI: 1.62–5.33) and perceived benefit of the COVID-19 vaccine (AOR = 1.89, 95% CI: 1.08–3.31), were found to be a significant association with the willingness to receive the COVID-19 vaccine among chronic patients. Conclusion This study confirms that around 55% of adult chronic patients were willing to receive the COVID-19 vaccine. Providing health education for chronic patients to emphasize the knowledge and attitude of the COVID-19 vaccine and raise patients’ perceived risk of COVID-19 and the benefit of the COVID-19 vaccine could be recommended to improve their willingness to COVID-19 vaccination.
The relationship between obstructive sleep apnoea and erectile dysfunction: An underdiagnosed link? A prospective cross‐sectional study

This cross‐sectional study aimed to investigate the prevalence and clinical characteristics of erectile dysfunction in patients with obstructive sleep apnoea. We enrolled 133 male patients with suspected obstructive sleep apnoea. Ear, nose and throat evaluation, laboratory tests, body mass index, Epworth sleepiness scale, 5‐international index of erectile function, overnight ambulatory polygraphy and drug‐induced sleep endoscopy patterns were assessed. Eighty patients reported obstructive sleep apnoea. 60% (n = 48) reported erectile dysfunction. Statistically significant correlations were found between 5‐International Index of Erectile Function and age, hypertension, diabetes, Epworth sleepiness scale, apnoea‐hypopnea index score, O2 saturation‐nadir, and oxygen desaturation index. Age, diabetes and O2 saturation‐nadir were independent predictors of erectile function. Epworth sleepiness scale, apnoea‐hypopnea index score, O2 saturation‐nadir, oxygen desaturation index and albumin were higher compared to patients without erectile dysfunction. No statistically significant differences were reported for drug‐induced sleep endoscopy patterns and erectile dysfunction. Patients with obstructive sleep apnoea were at significant risk of having erectile dysfunction. Males with obstructive sleep apnoea should be investigated for erectile dysfunction.
Design, effectiveness, and economic outcomes of contemporary chronic disease clinical decision support systems: a systematic review and meta-analysis

Abstract Objectives Electronic health record-based clinical decision support (CDS) has the potential to improve health outcomes. This systematic review investigates the design, effectiveness, and economic outcomes of CDS targeting several common chronic diseases. Material and Methods We conducted a search in PubMed (Medline), EBSCOHOST (CINAHL, APA PsychInfo, EconLit), and Web of Science. We limited the search to studies from 2011 to 2021. Studies were included if the CDS was electronic health record-based and targeted one or more of the following chronic diseases: cardiovascular disease, diabetes, chronic kidney disease, hypertension, and hypercholesterolemia. Studies with effectiveness or economic outcomes were considered for inclusion, and a meta-analysis was conducted. Results The review included 76 studies with effectiveness outcomes and 9 with economic outcomes. Of the effectiveness studies, 63% described a positive outcome that favored the CDS intervention group. However, meta-analysis demonstrated that effect sizes were heterogenous and small, with limited clinical and statistical significance. Of the economic studies, most full economic evaluations (n = 5) used a modeled analysis approach. Cost-effectiveness of CDS varied widely between studies, with an estimated incremental cost-effectiveness ratio ranging between USD$2192 to USD$151 955 per QALY. Conclusion We summarize contemporary chronic disease CDS designs and evaluation results. The effectiveness and cost-effectiveness results for CDS interventions are highly heterogeneous, likely due to differences in implementation context and evaluation methodology. Improved quality of reporting, particularly from modeled economic evaluations, would assist decision makers to better interpret and utilize results from these primary research studies. Registration PROSPERO (CRD42020203716)
A comparison of seasonal influenza and novel Covid-19 vaccine intentions: A cross-sectional survey of vaccine hesitant adults in England during the 2020 pandemic

ABSTRACT We compared intention to receive the seasonal influenza vaccine with a prospective coronavirus (COVID-19) vaccine among undecided or COVID-19 vaccine hesitant individuals to better understand the underlying differences and similarities in factors associated with vaccine intention. We delivered a cross-sectional online survey in October–November 2020. We included psychological constructs and sociodemographic variables informed by theory. We conducted pairwise comparisons and multiple linear regression models to explore associations between vaccine intention and psychological constructs. We recruited 1,660 participants, where 47.6% responded that they would likely receive the influenza vaccine, 31.0% that they would probably not accept the vaccination and 21.4% were unsure. In relation to the prospective COVID-19 vaccine, 39.0% responded that they would likely receive the vaccination, 23.7% that they would probably not accept the vaccination and 37.3% were unsure. Unique factors positively associated with COVID-19 vaccine intention were: perceived knowledge sufficiency about vaccine safety, beliefs about vaccine safety, and living in an area of low deprivation. The only unique factor positively associated with influenza intention was past influenza behavior. The strongest common predictors positively associated with intention were: favorable vaccine attitudes, the anticipated regret they may feel following infection if they were not to receive a vaccine, and the expectation from family or friends to accept the vaccine. Despite overall similarities in those factors associated with vaccination intention, we identified unique influences on intention. This additional insight will help support the planning and tailoring of future immunizations programmes for the respective viruses.
SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19

Abstract Brains of 42 COVID-19 decedents and 107 non-COVID-19 controls were studied. RT-PCR screening of 16 regions from 20 COVID-19 autopsies found SARS-CoV-2 E gene viral sequences in 7 regions (2.5% of 320 samples), concentrated in 4/20 subjects (20%). Additional screening of olfactory bulb (OB), amygdala (AMY) and entorhinal area for E, N1, N2, RNA-dependent RNA polymerase, and S gene sequences detected one or more of these in OB in 8/21 subjects (38%). It is uncertain whether these RNA sequences represent viable virus. Significant histopathology was limited to 2/42 cases (4.8%), one with a large acute cerebral infarct and one with hemorrhagic encephalitis. Case-control RNAseq in OB and AMY found more than 5000 and 700 differentially expressed genes, respectively, unrelated to RT-PCR results; these involved immune response, neuronal constituents, and olfactory/taste receptor genes. Olfactory marker protein-1 reduction indicated COVID-19-related loss of OB olfactory mucosa afferents. Iba-1-immunoreactive microglia had reduced area fractions in cerebellar cortex and AMY, and cytokine arrays showed generalized downregulation in AMY and upregulation in blood serum in COVID-19 cases. Although OB is a major brain portal for SARS-CoV-2, COVID-19 brain changes are more likely due to blood-borne immune mediators and trans-synaptic gene expression changes arising from OB deafferentation.
CORRECTION TO: “PARAMETRIC-REGRESSION–BASED CAUSAL MEDIATION ANALYSIS OF BINARY OUTCOMES AND BINARY MEDIATORS: MOVING BEYOND THE RARENESS OR COMMONNESS OF THE OUTCOME”

© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0 ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journalpermissions@oup.com. Vol. 191, No. 9
Incontinentia pigmenti and the eye

Purpose of Review: Incontinentia pigmenti (IP) is a rare X-linked dominant phakomatosis that predominately presents with dermatologic manifestations but can also cause central nervous system and ocular abnormalities. Awareness of the ocular complications of IP is crucial to identify ocular abnormalities early and prevent permanent vision loss. Recent Findings: There have been significant recent advances in ocular diagnostic imaging in IP. Optical coherence tomography (OCT) has helped characterize outer plexiform layer abnormalities in the macula, which can help explain central vision loss in IP patients. OCT angiography (OCT-A) also identifies macular vascular changes that induce these foveal structural abnormalities and may supplement fluorescein angiography, the current standard of care to identify peripheral retinal ischemia and neovascularization for infants with IP. Additionally, recent studies have presented excellent anatomic outcomes years after laser photocoagulation to ischemic retina. Early data indicates that antivascular endothelial growth factor therapy can induce retinal revascularization, but runs the risk of late recurrent neovascularization and requires long-term monitoring. Summary: Ophthalmic imaging is evolving in the evaluation of IP and is increasingly guiding treatment modalities. A particular focus on the ocular manifestations of IP has been the ideal treatment for retinopathy in this disorder.
Relational Care, Dementia, and Communication Challenges in Long-Term Care: A Meta-Ethnography

Abstract Few studies examine care as a relational process in long-term care, and still fewer describe the participation of residents with dementia. In this article, our objective was to understand the development of knowledge in this area by means of a meta-ethnography. Our search and selection process resulted in six eligible articles. Each documents a qualitative study of resident–staff interactions during care activities in a residential care setting, and includes participants with dementia. Tronto’s 4 Phases of Care were used to guide the identification of relational care practices within the articles selected. We identified five translatable concepts across the six studies: (1) doing with versus doing for, (2) staff responsiveness, (3) resident agency, (4) inclusive communication, and (5) time. In our new configuration of relational care, we combine these concepts to delineate an “interactive space” in which the agency of residents and initiative of staff are equally visible.
Baseline interleukin‐10, CD163, and tumor necrosis factor‐like weak inducer of apoptosis (TWEAK) gingival tissue levels in relation to clinical periodontal treatment outcomes: A 12‐week follow‐up study

Abstract Background The aim of this study was to examine the relationship between healing response after non‐surgical periodontal treatment and baseline gingival tissue levels of M2 macrophage activation‐related proteins CD163, interleukin (IL)‐10, interferon (IFN)‐γ, and tumor necrosis factor‐like weak inducer of apoptosis (TWEAK), and the CD163/TWEAK ratio. Methods Eighty‐eight gingival tissue samples from 44 Stage III/IV, Grade C periodontitis patients (18 smokers) and 41 tissue samples from 41 periodontally healthy participants (18 smokers) were evaluated. Clinical parameters were recorded in periodontally healthy individuals at baseline and in periodontitis patients at pre‐treatment and 2, 6, and 12 weeks following therapy. IL‐10, IFN‐γ, CD163, and TWEAK levels were analyzed with Luminex technique. Results Tissue levels (median, 1st–3rd quartile) of IL‐10 (pg/ng protein), CD163 (pg/μg protein) and TWEAK (pg/μg protein) were as follows: IL‐10 periodontitis: 2.08, 0.86–5.32 and periodontally healthy: 5.22, 3.20–10.25; CD163 periodontitis: 8.85, 4.92–14.06 and periodontally healthy: 18.36, 12.51‐34.02; TWEAK periodontitis: 0.08, 0.05–0.11 and periodontally healthy: 0.16, 0.12–0.21. IL‐10, CD163, and TWEAK levels were higher (P < 0.001) in periodontally healthy tissues than in periodontitis tissues. Pocket closure at 12 weeks was associated with elevated baseline gingival CD163 levels (P = 0.047) and CD163/TWEAK ratio (P = 0.001). Elevated baseline gingival CD163/TWEAK ratio was associated with pocket reduction at 6 (P = 0.022) and 12 weeks (P = 0.002). Conclusion Associations of pocket closure with pre‐treatment gingival tissue CD163 levels and CD163/TWEAK ratio indicate that baseline M2 macrophage activation profile may play a role in periodontal wound healing.
On the stability of stalled RNA polymerase and its removal by RapA

Abstract Stalling of the transcription elongation complex formed by DNA, RNA polymerase (RNAP) and RNA presents a serious obstacle to concurrent processes due to the extremely high stability of the DNA-bound polymerase. RapA, known to remove RNAP from DNA in an ATP-dependent fashion, was identified over 50 years ago as an abundant binding partner of RNAP; however, its mechanism of action remains unknown. Here, we use single-molecule magnetic trapping assays to characterize RapA activity and begin to specify its mechanism of action. We first show that stalled RNAP resides on DNA for times on the order of 106 seconds and that increasing positive torque on the DNA reduces this lifetime. Using stalled RNAP as a substrate we show that the RapA protein stimulates dissociation of stalled RNAP from positively supercoiled DNA but not negatively supercoiled DNA. We observe that RapA-dependent RNAP dissociation is torque-sensitive, is inhibited by GreB and depends on RNA length. We propose that stalled RNAP is dislodged from DNA by RapA via backtracking in a supercoiling- and torque-dependent manner, suggesting that RapA’s activity on transcribing RNAP in vivo is responsible for resolving conflicts between converging polymerase molecular motors.
Mortality in elderly patients starting hemodialysis program

Background: The incidence of older patients over 80 years old with chronic kidney disease who start hemodialysis (HD) program has been increasing in the last decade. Methods: We aimed to identify risk factors for morbidity and mortality in patients older than 80 years with end‐stage renal disease who started HD. We conducted a retrospective observational study of the Catalan Renal registry (RMRC). Results: A total of 2833 patients equal or older than 80 years (of 15,137) who started HD between 2002 and 2019 from the RMRC were included in the study. In this group, the first dialysis was performed through an arteriovenous fistula in 44%, percutaneous catheter in 28.2%, and tunneled catheter in 26.6%. Conventional dialysis was used in 65.7% and online HD in 34.3%. The most frequent cause of death was cardiac disease (21.8%), followed by social problems (20.4%) and infections (15.9%). Overall survival in older HD during the first year was 84% versus 91% in younger than 80 years (p < 0.001). Cox regression analysis identified the start of HD in the period 2002–2010, chronic obstructive pulmonary disease (COPD), and the onset of HD through vascular graft depicted as risk factors for first‐year mortality after dialysis initiation in patients older than 80 years with end‐stage renal disease who started HD. Conclusions: In conclusion, patients older than 80 years who started HD program had higher mortality, especially those who presented exacerbation of kidney disease, those with COPD, and those who started with a vascular graft.
New approach to heart failure in diabetes mellitus

Despite the introduction of complex pharmacological approaches, heart failure (HF) is still a therapeutic challenge, especially when it is associated with type 2 diabetes mellitus (T2DM). Recently, large clinical trials have shown multiple benefits from using sodium - glucose co -transporter-2 inhibitors and glucagon-like peptide-1 agonists not only in the field of diabetes but also as agents reducing the risk of cardiovascular events and the frequency of hospitalisation due to HF deterioration. This has been reflected in the recent American Heart Association (ACC) 2018 guidelines for risk reduction in patients with T2DM and cardiovascular diseases, and in the ACC/American Heart Association (AHA) 2019 guidelines for primary prevention of cardiovascular diseases.
Cross-sectional analysis of whole-brain microstructural changes in adult patients with bipolar and unipolar depression by diffusion kurtosis imaging

Rationale and Objectives More than half of the bipolar depression (BD) subjects are misdiagnosed as unipolar depression (UD) due to lack of objective diagnostic criteria. We aimed to identify microstructural neuronal changes differentiating BD from UD groups using diffusion kurtosis imaging (DKI). The objective of the study is to identify an objective neuro-imaging marker to differentiate BD from UD. Materials and Methods A prospective, cross-sectional study included total of 62 subjects with diagnosis of bipolar depression (n = 21), unipolar depression (n = 21), and healthy controls (n = 20). All subjects underwent diffusion-weighted imaging (b = 0,1000,2000) of the whole brain on 3-Tesla MR scanner. DKI data was analyzed using 189 region whole-brain atlas. Eight diffusion and kurtosis metrics including mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), and kurtosis fractional anisotropy (FKA) were measured against these 189 regions. Principle component analysis (PCA) was utilized to identify the most significant regions of the brain. ANOVA with post hoc tests was used for analyzing these regions. Results BD group showed increased MD, RD, decreased AK at the left amygdala and decreased MK and RK at the right hemi-cerebellum. UD group showed increased MK and RK at the right external capsule; and increased AK, MK, and RK at the right amygdala. Conclusion The right and left amygdala, right external capsule, and right hemi-cerebellum showed microstructural abnormalities capable of differentiating BD and UD groups. Diffusion imaging especially DKI can aid in management of depression patients.
Natural History of Friedreich Ataxia

Background and Objectives The understanding of the natural history of Friedreich ataxia (FRDA) has improved considerably recently, but patterns of neurologic deterioration are not fully clarified, compromising the assessment of the clinical relevance of effects and guidance for study design. The goal of this study was to acknowledge the broad genetic diversity of the population, especially for younger individuals, and to provide analyses stratified by age to guide population selection in future studies. Methods Based on a large natural history study, the FRDA Clinical Outcome Measures study that at the current data cut enrolled 1,115 participants, followed up for 5,287 yearly visits, we present results from the modified FRDA Rating Scale and its subscores. The secondary outcomes included the patient-reported activities of daily living scale, the timed 25-foot walk, and the 9-hole peg test. Long-term progression was modeled using slope analyses within early-onset, typical-onset, intermediate-onset, and late-onset FRDA. To reflect recruitment in clinical trials, short-term changes were analyzed within age-based subpopulations. All analyses were stratified by ambulation status. Results Long-term progression models stratified by disease severity indicated highly differential disease progression, especially at earlier ages at onset. In the ambulatory phase, decline was driven by axial items assessed by the Upright Stability subscore of the mFARS. The analyses of short-term changes showed slower progression with increasing population age due to decreasing genetic severity. Future clinical studies could reduce population diversity, interpatient variability, and the risk of imbalanced treatment groups by selecting the study population based on the functional capacity (e.g., ambulatory status) and by strict age-based stratification. Discussion The understanding of the diversity within FRDA populations and their patterns of functional decline provides an essential foundation for future clinical trial design including patient selection and facilitates the interpretation of the clinical relevance of progression detected in FRDA.
In vitro reconstitution reveals a key role of human mitochondrial EXOG in RNA primer processing

Abstract The removal of RNA primers is essential for mitochondrial DNA (mtDNA) replication. Several nucleases have been implicated in RNA primer removal in human mitochondria, however, no conclusive mechanism has been elucidated. Here, we reconstituted minimal in vitro system capable of processing RNA primers into ligatable DNA ends. We show that human 5′-3′ exonuclease, EXOG, plays a fundamental role in removal of the RNA primer. EXOG cleaves short and long RNA-containing flaps but also in cooperation with RNase H1, processes non-flap RNA-containing intermediates. Our data indicate that the enzymatic activity of both enzymes is necessary to process non-flap RNA-containing intermediates and that regardless of the pathway, EXOG-mediated RNA cleavage is necessary prior to ligation by DNA Ligase III. We also show that upregulation of EXOG levels in mitochondria increases ligation efficiency of RNA-containing substrates and discover physical interactions, both in vitro and in cellulo, between RNase H1 and EXOG, Pol γA, Pol γB and Lig III but not FEN1, which we demonstrate to be absent from mitochondria of human lung epithelial cells. Together, using human mtDNA replication enzymes, we reconstitute for the first time RNA primer removal reaction and propose a novel model for RNA primer processing in human mitochondria.