Miracle-dz/UniFAR-FTUs huggingface dataset:
Radiation Protection Evaluation of Medical X-ray Imaging Centers in Qazvin, Iran

Abstract Given the potential risks of x rays in imaging, it is necessary to evaluate the radiation safety of medical x-ray imaging rooms and radiation information of radiographers. A descriptive study has been carried out in Qazvin, Iran, in the form of a questionnaire answered by radiography technologists in private and public imaging centers to assess the level of knowledge, attitude, and performance about x-ray exposure and safety against it. Afterward, the radiation doses of public areas of the radiography centers were measured by a survey meter. A checklist was also completed, containing items about availability of ventilation facilities in x-ray rooms, radiation warning signs, radiation work schedules, documents of periodic blood test monitoring, exposure history of radiographers by film badge, and documents of the quality control of x-ray devices. The data analysis was performed by SPSS 16 using descriptive study, t-test, ANOVA, and Pearson’s correlation coefficient test. The mean attitude and knowledge scores were 6.65 ± 1.63 out of 9 and 4.82 ± 2.06 out of 15, respectively. Sex, age, and workplace had no significant effect on the radiographers’ knowledge and attitude, while occupational experience had a negative relationship, and level of education had a significant direct association with knowledge of the participants (p-value<0.05). The performance of the staff was somewhat good. Almost all x-ray imaging centers had good radiation protection conditions. The annual quality control of x-ray imaging devices was ensured. The radiation protection awareness among the medical radiographers in Qazvin city needs to be improved, especially among the experienced staff.
Effects of acute tocolysis using ritodrine hydrochloride on foetal heart rate patterns in intrauterine foetal resuscitation: a retrospective, single-centre observational study

Abstract No consistent recommendations concerning the preferred tocolytic agents for intrauterine foetal resuscitation are available. We evaluated the effects of acute tocolysis (AT) using ritodrine hydrochloride on foetal heart rate (FHR) patterns and neonatal outcomes. We retrospectively analysed the data of patients undergoing emergency caesarean section because of non-reassuring foetal status indicated by foetal scalp electrodes. Patients were classified into AT (ritodrine hydrochloride approximately 500 µg/min) and control groups with 15 and 12 participants, respectively. FHR patterns, Apgar scores, umbilical arterial analysis, and neonatal admission were compared. All participants had FHR category II; decelerations disappeared in all foetuses in the AT group, with no significant difference in neonatal outcomes. The AT group had a higher baseline FHR and lower short-term FHR variability than the control group, indicating foetal autonomic responses. Further studies are needed to clarify the effects of AT on FHR patterns, neonatal outcomes, and foetal and neonatal autonomic responses. Impact statement What is already known on this subject? The usefulness of acute tocolysis using ritodrine hydrochloride has been well-documented in several studies; however, such an application often induces side effects, such as maternal tachycardia, palpitations, and tremors. What the results of this study add? The short-term administration of ritodrine hydrochloride eliminated decelerations, with no significant difference in neonatal outcomes in pregnant women with foetal heart rate category II. Meanwhile, there were higher foetal heart rate and lower short-term foetal heart rate variability in pregnant women administered with ritodrine hydrochloride, indicating foetal autonomic responses. What the implications are of these findings for clinical practice and/or further research? Ritodrine hydrochloride administration, even for short-term, appears to be associated with foetal autonomic responses. Further studies with stratification of patient groups based on the severity and aetiology of non-reassuring foetal status, including pregnant women with foetal category III, would elucidate the risk and benefit of acute tocolysis using ritodrine hydrochloride, based on foetal heart rate patterns, neonatal outcomes, and foetal and neonatal autonomic responses.
Successful early treatment combining remdesivir with high‐titer convalescent plasma among COVID‐19‐infected hematological patients

Immunocompromised patients with hematological malignancies are at high risk for a severe course of COVID‐19 (Coronavirus Disease 2019) with a deadly outcome. With remdesivir use, several randomized trials have recorded abbreviated recovery periods, lower mortality, and positive consequences of early treatment initiation. Based on randomized trial results, the FDA has approved remdesivir for the treatment of COVID‐19. Regarding convalescent plasma (CP), evidence from recently published large trials implies that early administration of high‐titer CP is most efficacious. However, no published studies assessing the effect of remdesivir or CP in COVID‐19 have included a substantial proportion of hematooncology patients, and available data are limited to case reports. In view of this dearth of data, we decided to analyze the efficacy of early combination therapy of remdesivir and high‐titer CP among hematological patients. This treatment strategy was implemented after observing several grim COVID‐19 outcomes among these patients.
New Internet-Based Warfarin Anticoagulation Management Approach After Mechanical Heart Valve Replacement: Prospective, Multicenter, Randomized Controlled Trial

Background Mechanical heart valve replacement (MHVR) is an effective method for the treatment of severe heart valve disease; however, it subjects patient to lifelong warfarin therapy after MHVR with the attendant risk of bleeding and thrombosis. Whether internet-based warfarin management reduces complications and improves patient quality of life remains unknown. Objective This study aimed to compare the effects of internet-based warfarin management and the conventional approach in patients who received MHVR in order to provide evidence regarding alternative strategies for long-term anticoagulation. Methods This was a prospective, multicenter, randomized, open-label, controlled clinical trial with a 1-year follow-up. Patients who needed long-term warfarin anticoagulation after MHVR were enrolled and then randomly divided into conventional and internet-based management groups. The percentage of time in the therapeutic range (TTR) was used as the primary outcome, while bleeding, thrombosis, and other events were the secondary outcomes. Results A total of 721 patients were enrolled. The baseline characteristics did not reach statistical differences between the 2 groups, suggesting the random assignment was successful. As a result, the internet-based group showed a significantly higher TTR (mean 0.53, SD 0.24 vs mean 0.46, SD 0.21; P<.001) and fraction of time in the therapeutic range (mean 0.48, SD 0.22 vs mean 0.42, SD 0.19; P<.001) than did those in the conventional group. Furthermore, as expected, the anticoagulation complications, including the bleeding and embolic events had a lower frequency in the internet-based group than in the conventional group (6.94% vs 12.74%; P=.01). Logistic regression showed that internet-based management increased the TTR by 7% (odds ratio [OR] 1.07, 95% CI 1.05-1.09; P<.001) and reduced the bleeding and embolic risk by 6% (OR 0.94, 95% CI 0.92-0.96; P=.01). Moreover, low TTR was found to be a risk factor for bleeding and embolic events (OR 0.87, 95% CI 0.83-0.91; P=.005). Conclusions The internet-based warfarin management is superior to the conventional method, as it can reduce the anticoagulation complications in patients who receive long-term warfarin anticoagulation after MHVR. Trial Registration Chinese Clinical Trial Registry ChiCTR1800016204; http://www.chictr. org.cn/showproj.aspx? proj=27518 International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2019-032949
Characteristics of pain and the burden it causes in patients with amyotrophic lateral sclerosis – a longitudinal study

Abstract Objective Pain currently plays a subordinate role in the clinical care of patients with ALS. We aim to examine epidemiological and clinical characteristics of pain as well as its impact throughout the disease course. Methods During a longitudinal follow-up at three time points, 151 ALS patients from three German outpatient clinics completed the Brief Pain Inventory, ALS-Functional Rating Scale-Extension and ALS Depression Inventory. Analysis of variance and covariance with repeated measures were performed. Results Pain was prevalent in 56% of the 151 patients at baseline and in 70% of the remaining 40 patients at the third survey. Of the 28 patients with pain who participated in all three surveys, about two thirds suffered from an average pain intensity corresponding to at least moderate pain on the numerical rating scale (NRS ≥ 4). Patients reported different pain qualities and localized the pain most frequently in the extremities, back and neck. Pain moderately impaired the functions of daily living. Pain intensity, pain quality and pain-related impairment did not significantly change over time. One third of the patients suffered from clinically relevant depressive symptoms. However, there was no conclusive evidence of a link between pain intensity and depressive symptoms. Conclusion Pain is frequent and constitutes an additional strain on ALS patients who have to endure a rapidly progressive and severely debilitating disease. This study contributes to better understanding of the characteristics of pain and its impact on ALS patients throughout the disease course and may thus help to more effectively address this symptom.
Mathematical modelling of mitotic controls

The mitotic cell cycle is fundamental to eukaryotic life. In mitosis, replicated chromosomes are segregated to form two new nuclei. This is essential to ensure the maintenance of chromosome number between parent and daughter cells. In higher eukaryotes, numerous cytological changes occur to facilitate the separation of the genetic material: the nuclear envelope breaks down, the mitotic spindle assembles, and the cell rounds-up. There is a well-conserved control network that regulates these processes to bring about the entry into mitosis, the separation of the genetic material, and the reversal of these processes during mitotic exit. To build a coherent model of these regulatory networks requires us to write the biochemical reactions in mathematical form. The work in this Thesis pertains to three fundamental switches: entry into mitosis, the metaphase-to-anaphase transition, and exit from mitosis. I present three studies from a systems-level perspective. The first investigates a novel bistable mechanism controlling mitotic entry/exit in vitro using purified proteins. Dephosphorylation of Greatwall kinase by the phosphatase PP2A-B55 creates a double negative feedback loop that gives a bistable system response with respect to cyclin-dependent kinase 1 (Cdk1) activity. The second looks at hysteresis between mitotic entry and mitotic exit in HeLa cells. Hysteresis persists when either of the regulatory loops of Cdk1 or its counter-acting phosphatase PP2A-B55 is removed, but is diminished when they are both removed. Finally, the regulation of separase in the metaphase-to-anaphase transition is analysed. Separase that is liberated from securin inhibition is isomerised by Pin1 into a conformation that can bind to cyclin B1. This binding peaks after separase has cleaved cohesin and initiated anaphase.
Morphometric variance, evolutionary constraints and their change through time in Late Devonian Palmatolepis conodonts

Phenotypic variation is the raw material of evolution. Standing variation can facilitate response to selection along “lines of least evolutionary resistance”, but selection itself might alter the structure of the variance. Shape was quantified using 2D geometric morphometrics in Palmatolepis conodonts through the Late Devonian period. Patterns of variance were characterized along the record by the variance‐covariance matrix (P‐matrix) and its first axis (Pmax). The Late Frasnian was marked by environmental oscillations culminating with the Frasnian/Famennian mass extinction. A shape response was associated with these fluctuations, together with a deflection of the Pmax and the P‐matrix. Thereafter, along the Famennian, Palmatolepis mean shape shifted from broad elements with a large platform to slender elements devoid of platform. This shift in shape was associated with a reorientation of Pmax and the P‐matrix, due to profound changes in the functioning of the elements selecting for new types of variants. Both cases provide empirical evidences that moving adaptive optimum can reorient phenotypic variation, boosting response to environmental changes. On such time scales, the question seems thus not to be whether the P‐matrix is stable, but how it is varying in response to changes in selection regimes and shifts in adaptive optimum.
Natural Bioactive as a Potential Therapeutic Approach for the Management of Cyclophosphamide-induced Cardiotoxicity.

Cyclophosphamide (CP) is an extensively used anticancer drug, but its cardiotoxic manifestation is a major concern for its widespread clinical use. The observed cardiotoxic attributes have been reported at the therapeutic dose and often result into a high mortality rate and poor clinical outcome. Fall in the level of antioxidant enzymes catalase (CAT), reduced glutathione (GSH), superoxide dismutase (SOD) generation of reactive oxygen species (ROS), inflammatory cytokines nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB), tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), apoptotic proteins (caspases) and direct damage to myocardial tissue (histological and ultrastructural damage) are some of the reported manifestations of cardiotoxicity. The observed clinical attributes of CP-induced cardiotoxicity are myocarditis, hemorrhage, thrombosis, myocardial infarction (MI), reduced ejection fraction, altered electrocardiogram (ECG) reading and heart failure. However, unlike Daxarazasone (an adjuvant to reduce doxorubicin-induced cardiotoxicity) no approved adjuvant is available to mitigate CP-induced cardiotoxicity. Thus, various natural bioactives have been explored for the possible cardioprotective effect against CP-induced cardiotoxicity. In the current manuscript, we have discussed the clinical and preclinical aspects of CP-induced cardiotoxicity, its various clinically used combination with other anticancer drugs, and the available therapeutic regimen to mitigate this cardiotoxicity. Further, we discussed the limitations of available synthetic drugs used as an adjuvant and discussed various natural bioactive and their experimental details. This manuscript's overall goal is to throw light on CP-induced cardiotoxicity and summarize all the experimental data so that researchers working in this field may scientifically get up-to-date information at one place.
Optimizing Positivity Thresholds for a Risk-Adapted Screening Strategy in Colorectal Cancer Screening

INTRODUCTION: Risk-adapted screening combining the Asia-Pacific Colorectal Screening score, fecal immunochemical test (FIT), and colonoscopy improved the yield of colorectal cancer screening than FIT. However, the optimal positivity thresholds of risk scoring and FIT of such a strategy warrant further investigation. METHODS: We included 3,407 participants aged 50–74 years undergoing colonoscopy from a colorectal cancer screening trial. For the risk-adapted screening strategy, subjects were referred for subsequent colonoscopy or FIT according to their risk scores. Diagnostic performance was evaluated for FIT and the risk-adapted screening method with various positivity thresholds. Furthermore, a modeled screening cohort was established to compare the yield and cost using colonoscopy, FIT, and the risk-adapted screening method in a single round of screening. RESULTS: Risk-adapted screening method had higher sensitivity for advanced neoplasm (AN) (27.6%–76.3% vs 13.8%–17.3%) but lower specificity (46.6%–90.8% vs 97.4%–98.8%) than FIT did. In a modeled screening cohort, FIT-based screening would be slightly affected because the threshold varied with a reduction of 76.0%–80.9% in AN detection and 82.0%–84.4% in cost when compared with colonoscopy. By contrast, adjusting the threshold of Asia-Pacific Colorectal Screening score from 3 to 5 points for risk-adapted screening varied from an increase of 12.6%–14.1% to a decrease of 55.6%–60.1% in AN detection, with the reduction of cost from 4.2%–5.3% rising to 66.4%–68.5%. DISCUSSION: With an appropriate positivity threshold tailored to clinical practice, the risk-adapted screening could save colonoscopy resources and cost compared with the colonoscopy-only and FIT-only strategies.
Astigmatic change as a predictor of intrastromal corneal ring segment late extrusion

ICRS placement is a reversible procedure, even after a long-term implantation. A change in refractive astigmatism is a clinical predisposing factor of ICRS extrusion. Purpose: To evaluate changes in keratoconic corneas implanted with intrastromal corneal ring segments (ICRSs) that have been explanted because of late extrusion of the segment after >2 years. Setting: Vissum Miranza, Alicante, Spain; OftalmoSalud, Lima, Peru; Minya University Hospital, Egypt. Design: Retrospective multicenter case series. Methods: 23 keratoconic corneas that were implanted for ≥2 years and explanted because of natural extrusion of the segment. Clinical measures of visual, refractive, topographic, pachymetric, and aberrometric data were analyzed. To perform exploratory factor analysis, the Kaiser-Meyer-Olkin (KMO) test was used to evaluate sampling adequacy. Factor analysis with VARIMAX rotation was used to determine the main factors of the inventory. Results: The mean time interval was 5 years. Topographic findings were reversed nearly to the baseline level after segment explantation (Km: 48.97 ± 3.47 D pre implantation and 47.60 ± 3.67 D after explantation, P =.374). Significant worsened in refractive cylinder was found pre-ICRS extrusion (‒2.54 ± 3.40 D after implantation and ‒3.96 ± 1.72 before extrusion, P < .05). The main factor obtained in the preimplantation moment included keratoconus grade, keratometric readings, and visual acuities. After ICRS implantation, the most strength components were the refractive cylinder, corrected distance visual acuity, and uncorrected distance visual acuity. Corneal aberrations were the main factors in the pre-explantation analysis. Conclusions: ICRSs were safely extracted, with a reversal of the corneal topographic data to the preoperative level. A significant astigmatic change was shown in patients implanted with ICRSs before late extrusion of the segment, suggesting the role of this parameter as a prognostic factor of extrusion.
Association Between Longitudinal Blood Pressure Trajectory and the Progression of Chronic Kidney Disease: Results From the KNOW-CKD

Supplemental Digital Content is available in the text. Studies on the longitudinal temporal trend of blood pressure (BP) and its impact on kidney function are scarce. Here, we evaluated the association of dynamic changes in systolic blood pressure (SBP) over time with adverse kidney outcomes. We analyzed 1837 participants from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease). The main exposure was 3 distinct SBP trajectories determined by the latent class mixed model (decreasing, stable, and increasing) using 3 SBP measurements at 0, 6, and 12 months. The primary outcome was CKD progression, defined as a composite of halving estimated glomerular filtration rate from baseline value or onset of end-stage kidney disease. SBP declined from 144 to 120 mm Hg in the decreasing SBP trajectory group and rose from 114 to 136 mm Hg in the increasing trajectory group within 1 year. During 6576 person-years of follow-up (median, 3.7 years), the composite outcome occurred in 521 (28.4%) participants. There were fewer primary outcome events in the decreasing (30.6%) and stable (26.5%) SBP trajectory groups than in the increasing trajectory group (33.0%). In the multivariable-adjusted cause-specific hazards model, increasing SBP trajectory was associated with a 1.28-fold higher risk for adverse kidney outcome compared with stable SBP trajectory. However, the risk for the primary outcome did not differ between the decreasing and stable SBP trajectory groups. In this longitudinal CKD cohort study, compared with stable SBP trajectory, increasing SBP trajectory was associated with higher risk for adverse kidney outcome, whereas decreasing SBP trajectory showed similar risk.
Neurofilament light chain and glial fibrillary acidic protein levels in metachromatic leukodystrophy

Abstract Metachromatic leukodystrophy is a lethal metabolic leukodystrophy, with emerging treatments for early disease stages. Biomarkers to measure disease activity are required for clinical assessment and treatment follow-up. This retrospective study compared neurofilament light chain and glial fibrillary acidic protein (GFAP) levels in CSF (n = 11) and blood (n = 92) samples of 40 patients with metachromatic leukodystrophy (aged 0–42 years) with 38 neurologically healthy children (aged 0–17 years) and 38 healthy adults (aged 18–45 years), and analysed the associations between these levels with clinical phenotype and disease evolution in untreated and transplanted patients. Metachromatic leukodystrophy subtype was determined based on the (expected) age of symptom onset. Disease activity was assessed by measuring gross motor function deterioration and brain MRI. Longitudinal analyses with measurements up to 23 years after diagnosis were performed using linear mixed models. CSF and blood neurofilament light chain and GFAP levels in paediatric controls were negatively associated with age (all P < 0.001). Blood neurofilament light chain level at diagnosis (median, interquartile range; picograms per millilitre) was significantly increased in both presymptomatic (14.7, 10.6–56.7) and symptomatic patients (136, 40.8–445) compared to controls (5.6, 4.5–7.1), and highest among patients with late-infantile (456, 201–854) or early-juvenile metachromatic leukodystrophy (291.0, 104–445) and those ineligible for treatment based on best practice (291, 57.4–472). GFAP level (median, interquartile range; picogram per millilitre) was only increased in symptomatic patients (591, 224–1150) compared to controls (119, 78.2–338) and not significantly associated with treatment eligibility (P = 0.093). Higher blood neurofilament light chain and GFAP levels at diagnosis were associated with rapid disease progression in late-infantile (P = 0.006 and P = 0.051, respectively) and early-juvenile patients (P = 0.048 and P = 0.039, respectively). Finally, blood neurofilament light chain and GFAP levels decreased during follow-up in untreated and transplanted patients but remained elevated compared with controls. Only neurofilament light chain levels were associated with MRI deterioration (P < 0.001). This study indicates that both proteins may be considered as non-invasive biomarkers for clinical phenotype and disease stage at clinical assessment, and that neurofilament light chain might enable neurologists to make better informed treatment decisions. In addition, neurofilament light chain holds promise assessing treatment response. Importantly, both biomarkers require paediatric reference values, given that their levels first decrease before increasing with advancing age.