Miracle-dz/UniFAR-FTUs huggingface dataset:
Self-management interventions for adults living with Chronic Obstructive Pulmonary Disease (COPD): The development of a Core Outcome Set for COMPAR-EU project

Background A large body of evidence suggests that self-management interventions (SMIs) may improve outcomes in chronic obstructive pulmonary disease (COPD). However, accurate comparisons of the relative effectiveness of SMIs are challenging, partly due to heterogeneity of outcomes across trials and uncertainty about the importance of these outcomes for patients. We aimed to develop a core set of patient-relevant outcomes (COS) for SMIs trials to enhance comparability of interventions and ensure person-centred care. Methods We undertook an innovative approach consisting of four interlinked stages: i) Development of an initial catalogue of outcomes from previous EU-funded projects and/or published studies, ii) Scoping review of reviews on patients and caregivers’ perspectives to identify outcomes of interest, iii) Two-round Delphi online survey with patients and patient representatives to rate the importance of outcomes, and iv) Face-to-face consensus workshop with patients, patient representatives, health professionals and researchers to develop the COS. Results From an initial list of 79 potential outcomes, 16 were included in the COS plus one supplementary outcome relevant to all participants. These were related to patient and caregiver knowledge/competence, self-efficacy, patient activation, self-monitoring, adherence, smoking cessation, COPD symptoms, physical activity, sleep quality, caregiver quality of life, activities of daily living, coping with the disease, participation and decision-making, emergency room visits/admissions and cost effectiveness. Conclusion The development of the COPD COS for the evaluation of SMIs will increase consistency in the measurement and reporting of outcomes across trials. It will also contribute to more personalized health care and more informed health decisions in clinical practice as patients’ preferences regarding COPD outcomes are more systematically included.
Formation of hydroxy‐sulfates from pyrite in coastal acid sulfate soil environments in Malaysia

Abstract Pyrite in hydromorphic soils is oxidized when it is exposed to the atmosphere. The sulfide oxidation releases hydrogen (H+) ions and other ions into the aqueous solution, and subsequently hydroxy‐sulfates are formed. A laboratory aging experiment was conducted using coastal sulfate‐rich soils in Malaysia to identify and determine the nature and composition of the hydroxy‐sulfates and to explain the mechanism of their formation. Powder X‐ray diffraction (XRD) analysis showed that incubating the pyrite‐bearing soils in the presence of added electrolyte (KCl and NaCl) resulted in the formation of jarosite, natrojarosite, and/or alunite. Subsequent transmission electron microscopy‐energy dispersive X‐ray (TEM‐EDAX) analysis showed that a hydroxy‐sulfate crystal was composed mainly of hydrogen (H), oxygen (O), sodium (Na), aluminum (Al), sulfur (S), potassium (K), and iron (Fe) which was accounted for as jarosite, natrojarosite, and/or alunite by powder XRD. The small amount of fluorine (F), nickel (N.
Successful use of blind bronchial aspiration and hyperinflation to treat postoperative right lung atelectasis in infants

To the Editor, Patients undergoing abdominal operations are at a risk for developing pulmonary complications. Postextubation atelectasis occurs commonly and is managed by chest physiotherapy techniques like incentive spirometry, deep breathing exercises, gravity‐assisted postural drainage therapy, nebulization, and adequate analgesia. The use of lung expansion techniques which require patient cooperation is limited in infants. Also, the incidence of atelectasis in infants is higher due to smaller airways, thick secretions, and impaired mucociliary clearance. Postoperative atelectasis leads to prolonged hospital stay, need for noninvasive/invasive ventilation, and nosocomial infections, which adversely affect the clinical course. We used a simple nonbronchoscopic method consisting of a short intubation maneuver and blind bronchial aspiration (SIMBA) to re‐expand right lung atelectasis refractory to conservative physiotherapy in two infants, postoperatively.
Numerical Simulation of Countercurrent Gas-Liquid Flow in a PWR Hot Leg under Reflux Cooling

In reflux cooling, the steam generated in the reactor core and the water condensed in a steam generator form a countercurrent flow in a hot leg. In order to investigate flow patterns in the hot leg under countercurrent flow conditions, countercurrent air-water tests were previously conducted using a 1/15th scale model of a PWR hot leg. Numerical simulation results for the tests using a three-dimensional twofluid model in FLUENT6.3. 26, implemented with an appropriate set of correlations for the gas-liquid interfacial friction, were in good agreement with the measured data. In the present study, further numerical simulations were carried out for a full-scale hot leg under PWR plant conditions to investigate the effects of pipe diameter and fluid properties. The predicted countercurrent flow limitation characteristics were well correlated with the Wallis parameters and agreed well with the measured data from the 1/15th scale air-water tests as well as the full-scale steam-water UPTF tests. The results indicate that the set of correlations for the gas-liquid interfacial friction can be utilized to simulate countercurrent flows in the full-scale PWR hot leg.
Discrepancies in child and parent reporting of concussion symptoms

ABSTRACT Objective: To assess discrepancies between child and parent symptom reports following concussion. Methods: Prospective cohort study involving 61 patients, age 7–21 years, diagnosed with a concussion within the previous 14 days. Children/parents completed the Child SCAT-3 symptom inventory at enrollment and 4 weeks post-injury. A within-subjects t-test was used to compare differences in child/parent response for each of 20 individual symptoms, 4 symptom domains, and total symptom severity. Pearson correlations were used to measure agreement between child/parent responses. A repeated measures analysis of variance assessed the effect of time on child/parent symptom discrepancy. Results: At enrollment, children reported higher symptom severity for ‘distracted easily’ (adj. p = .015) and ‘confused’ (adj. p = .015). There was moderate-to-high (r > 0.3) agreement between children and parents for more individual symptoms at enrollment (18/20) than at 4 weeks post-injury (14/20). Age had no effect (p > .05) on the discrepancy between child/parent reports. Conclusions: Although there was moderate-to-strong agreement between child/parent reports of concussion symptoms, discrepancies in individual cognitive symptom reports exist, in both children and adolescents. Therefore, collection of parent scales may provide useful information when tracking cognitive symptoms in adolescent patients, who may under-report or under-recognize cognitive deficits.
The effects of a group exercise and education programme on symptoms and physical fitness in patients with fibromyalgia: a prospective observational cohort study

Abstract Purpose Given the limited attention on a combined exercise and education approach for those with chronic musculoskeletal pain disorder such as fibromyalgia, the purpose of this was to evaluate the efficacy of a combined exercise and education programme on symptoms and physical fitness in participants with fibromyalgia. Materials and methods Using a prospective observational cohort study, participants with fibromyalgia (n = 75) volunteered. The 6-minute-walk-test (6MWT) and revised-fibromyalgia-impact-questionnaire (FIQR) were used before, after (6 weeks) and 6-months post an exercise and education programme. Results Forty-three participants (age = 49.7 ± 15.2 y) completed the 6-week programme, with improvements observed for the 6MWT (67 m, p < 0.001) and FIQR (11 AU, p < 0.001), though only two (6MWT) and five (FIQR) participants, respectively, achieved the minimal clinically important difference (MCID). Using 74% of the intial sample, a small-to-moderate improvement in scores were observed across the 6-month period for the 6MWT (37 m, p = 0.002) and FIQR (3 AU, p = 0.01), with only two participants achieving the MCID for the 6MWT. Conclusions The results in this study indiciate small-to-moderate improvements in the 6MWT and FIQR after a combined exercise and education programme, with direct delivery being more effective. Implications for rehabilitation A six-week exercise and education programme elicited moderate, short-term (6 weeks) benefits on physical fitness and key symptoms in patients with fibromyalgia. On average, these benefits were sustained in the long-term (6 months) following the programme but were small-to-moderate and lower than the MCID. Regular follow-up may be required to improve adherence to the education and exercise programme and maintain or increase the observed improvements in 6MWT and FIQR.
Chidamide induces apoptosis in DLBCL cells by suppressing the HDACs/STAT3/Bcl-2 pathway

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignant tumor type, and epigenetic modifications such as acetylation or deacetylation serve vital roles in its development. Chidamide, a novel histone deacetylase inhibitor, exerts an anticancer effect against various types of cancer. The present study aimed to evaluate the cellular effect of chidamide on a number of DLBCL cell lines and to investigate its underlying mechanism. The results demonstrated that chidamide induced the death of these cells in a concentration-(0–30 µmol/l) and time-dependent (24–72 h) manner, as determined using the Cell Counting Kit-8 cell viability assay. Moreover, chidamide promoted cellular apoptosis, which was identified via flow cytometry and western blot analysis, with an increase in cleaved caspase-3 expression and a decrease in Bcl-2 expression. Chidamide treatment also decreased the expression level of STAT3 and its phosphorylation, which was accompanied by the downregulation of a class-I histone deacetylase (HDAC) inhibitor, chidamide. Collectively, these data suggested that chidamide can be a potent therapeutic agent to treat DLBCL by inducing the apoptotic death of DLBCL cells by inhibiting the HDACs/STAT3/Bcl-2 pathway.
International Collaboration to Ensure Equitable Access to Vaccines for COVID‐19: The ACT‐Accelerator and the COVAX Facility

Policy Points Equitable access to a COVID‐19 vaccine in all countries remains a key policy objective, but experience of previous pandemics suggests access will be limited in developing countries, despite the rapid development of three successful vaccine candidates. The COVAX Facility seeks to address this important issue, but the prevalence of vaccine nationalism threatens to limit the ability of the facility to meet both its funding targets and its ambitious goals for vaccine procurement. A failure to adequately address the underlying lack of infrastructure in developing countries threatens to further limit the success of the COVAX Facility. Context Significant effort has been directed toward developing a COVID‐19 vaccine, which is viewed as the route out of the pandemic. Much of this effort has coalesced around COVAX, the multilateral initiative aimed at accelerating the development of COVID‐19 vaccines, and ensuring they are equitably available in low‐ and middle‐income countries (LMICs). This paper represents the first significant analysis of COVAX, and the extent to which it can be said to have successfully met these aims. Methods This paper draws on the publicly available policy documents made available by the COVAX initiatives, as well as position papers and public statements from governments around the world with respect to COVID‐19 vaccines and equitable access. We analyze the academic literature regarding access to vaccines during the H1N1 pandemic. Finally, we consider the WHO Global Allocation System, and its principles, which are intended to guide COVAX vaccine deployment. Findings We argue that the funding mechanism deployed by the COVAX Pillar appears to be effective at fostering at‐risk investments in research and development and the production of doses in advance of confirmation of clinical efficacy, but caution that this represents a win‐win situation for vaccine manufacturers, providing them with opportunity to benefit regardless of whether their vaccine candidate ever goes on to gain regulatory approval. We also argue that the success of the COVAX Facility with respect to equitable access to vaccine is likely to be limited, primarily as a result of the prevalence of vaccine nationalism, whereby countries adopt policies which heavily prioritize their own public health needs at the expense of others. Conclusions Current efforts through COVAX have greatly accelerated the development of vaccines against COVID‐19, but these benefits are unlikely to flow to LMICs, largely due to the threat of vaccine nationalism.
Association of platelet count and plateletcrit with nerve conduction function and peripheral neuropathy in patients with type 2 diabetes mellitus

Diabetes has been considered as a ‘pro‐thrombotic state’ with enhanced platelet reactivity. Abnormality in platelet aggregation has been found in patients with its most common chronic complication – diabetic peripheral neuropathy (DPN). The purpose of this study was to investigate the potential association of platelet indices with nerve conduction function and the presence of DPN in Chinese patients with type 2 diabetes mellitus.
Construction of a MoxC/Ni Network Electrode with Low Overpotential for Hydrogen Generation

The integration of commercial photovoltaic devices and electrocatalysts has attracted considerable interest to realize the conversion of solar power to renewable hydrogen energy. However, a noble metal electrocatalyst (Pt) is too expensive and rare, which inspires the development of efficient and economical catalytic electrodes. Herein, we have fabricated a 3 D MoxC/Ni network through the carbonization of a polyaniline–Mo7O24 precursor, which was electrochemically deposited on Ni foam in advance. If the 3 D MoxC/Ni network is used as a catalytic electrode for the hydrogen evolution reaction (HER), a low onset potential of approximately 44 mV for driving 1 mA cm−2 of current density and a Tafel slope of approximately 49 mV decade−1 (overpotential η=50–60 mV) are obtained. Moreover, the apparent exchange current density reaches approximately 0.1 mA cm−2. After a long‐term HER test at η=100 mV or 500 CV sweeps, no deactivation is observed. This excellent electrocatalytic performance of the 3 D MoxC/Ni network promotes it as a promising earth‐abundant HER electrode.
In vitro and ex vivo anti-tumor effect and mechanism of Tucatinib in leukemia stem cells and ABCG2-overexpressing leukemia cells

Leukemia stem cells (LSCs), which evade standard chemotherapy, may lead to chemoresistance and disease relapse. The overexpression of ATP-binding cassette subfamily G member 2 (ABCG2) is an important determinant of drug resistance in LSCs and it can serve as a marker for LSCs. Targeting ABCG2 is a potential strategy to selectively treat and eradicate LSCs, and, hence, improve leukemia therapy. Tucatinib (Irbinitinib) is a novel tyrosine kinase inhibitor, targeting ErbB family member HER2, and was approved by the Food and Drug Administration in April 2020, and in Switzerland in May 2020 for the treatment of HER2-positive breast cancer. In the present study, the results demonstrated that tucatinib significantly improved the efficacy of conventional chemotherapeutic agents in ABCG2-overexpressing leukemia cells and primary leukemia blast cells, derived from patients with leukemia. In addition, tucatinib markedly decreased the proportion of leukemia stem cell-like side population (SP) cells. In SP cells, isolated from leukemia cells, the intracellular accumulation of Hoechst 33342, which is an ABCG2 substrate, was significantly elevated by tucatinib. Furthermore, tucatinib notably inhibited the efflux of [3H]-mitoxantrone and, hence, there was a higher level of [3H]-mitoxantrone in the HL60/ABCG2 cell line. The result from the ATPase assay revealed that tucatinib may interact with the drug substrate-binding site and stimulated ATPase activity of ABCG2. However, the protein expression level and cellular location of ABCG2 were not affected by tucatinib treatment. Taken together, these data suggested that tucatinib could sensitize conventional chemotherapeutic agents, in ABCG2-overexpressing leukemia cells and LSCs, by blocking the pump function of the ABCG2 protein. The present study revealed that combined treatment with tucatinib and conventional cytotoxic agents could be a potential therapeutic strategy in ABCG2-positive leukemia.
Meiosis Resumption of Immature Human Oocytes following Treatment with Calcium Ionophore In Vitro

Objective: In vitro maturation (IVM) of human oocytes is used to induce meiosis progression in immature retrieved oocytes. Calcium (Ca2+) has a central role in oocyte physiology. Passage through meiosis phase to another phase is controlled by increasing intracellular Ca2+. Therefore, the current research was conducted to evaluate the role of calcium ionophore (CI) on human oocyte IVM. Materials and Methods: In this clinical trial study, immature human oocytes were obtained from 216 intracytoplasmic sperm injection (ICSI) cycles. After ovarian stimulation, germinal vesicle (GV) stage oocytes were collected and categorized into two groups: with and without 10 µM CI treatment. Next, oocyte nuclear maturation was assessed after 24–28 hours of culture. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to assess the transcript profile of several oocyte maturation-related genes (MAPK3, CCNB1, CDK1, and cyclin D1 [CCND1]) and apoptotic-related genes (BCL-2, BAX, and Caspase-3). Oocyte glutathione (GSH) and reactive oxygen species (ROS) levels were assessed using Cell Tracker Blue and 2’,7’-dichlorodihydrofluorescein diacetate (H2DCFDA) fluorescent dye staining. Oocyte spindle configuration and chromosome alignment were analysed by immunocytochemistry. Results: The metaphase II (MII) oocyte rate was higher in CI‐treated oocytes (73.53%) compared to the control (67.43%) group, but this difference was not statistically significant (P=0.13). The mRNA expression profile of oocyte maturation-related genes (MAPK3, CCNB1, CDK1, and CCND1) (P<0.05) and the anti-apoptotic BCL-2 gene was remarkably up-regulated after treatment with CI (P=0.001). The pro-apoptotic BAX and Caspase-3 relative expression levels did not change significantly. The CI‐treated oocyte cytoplasm had significantly higher GSH and lower ROS (P<0.05). There was no statistically significant difference in meiotic spindle assembly and chromosome alignment between CI treatment and the control group oocytes. Conclusion: The finding of the current study supports the role of CI in meiosis resumption of human oocytes. (Registration Number: IRCT20140707018381N4)
Effect of lithium on circadian rhythm in bipolar disorder: A systematic review and meta‐analysis

Circadian rhythm disruption is commonly reported in patients with bipolar disorder. Lithium has been suggested to have effects on the circadian clock, the biological basis of the circadian rhythm. The objective of the current review was to review systematically the existing studies on the effect of lithium on circadian rhythm in patients with bipolar disorder.
End-of-treatment PET/CT predicts PFS and OS in DLBCL after first-line treatment: results from GOYA.

GOYA was a randomized phase 3 study comparing obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) vs standard-of-care rituximab plus CHOP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL). This retrospective analysis of GOYA aimed to assess the association between progression-free survival (PFS) and overall survival (OS) with positron emission tomography (PET)-based complete response (CR) status. Overall, 1418 patients were randomly assigned to receive 8 21-day cycles of obinutuzumab (n = 706) or rituximab (n = 712) plus 6 or 8 cycles of CHOP. Patients received a mandatory fluoro-2-deoxy-d-glucose-PET/computed tomography scan at baseline and end of treatment. After a median follow-up of 29 months, the numbers of independent review committee-assessed PFS and OS events in the entire cohort were 416 (29.3%) and 252 (17.8%), respectively. End-of-treatment PET CR was highly prognostic for PFS and OS according to Lugano 2014 criteria (PFS: hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.19-0.38; P < .0001; OS: HR, 0.12; 95% CI, 0.08-0.17; P < .0001), irrespective of international prognostic index score and cell of origin. In conclusion, the results from this prospectively acquired large cohort corroborated previously published data from smaller sample sizes showing that end-of-treatment PET CR is an independent predictor of PFS and OS and a promising prognostic marker in DLBCL. Long-term survival analysis confirmed the robustness of these data over time. Additional meta-analyses including other prospective studies are necessary to support the substitution of PET CR for PFS as an effective and practical surrogate end point. This trial was registered at www.clinicaltrials. gov as #NCT01287741.
Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers

The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we generated and integrated single‐cell transcriptomic and proteomic data from multiple large pulmonary fibrosis patient cohorts. Integration of 233,638 single‐cell transcriptomes (n = 61) across three independent cohorts enabled us to derive shifts in cell type proportions and a robust core set of genes altered in lung fibrosis for 45 cell types. Mass spectrometry analysis of lung lavage fluid (n = 124) and plasma (n = 141) proteomes identified distinct protein signatures correlated with diagnosis, lung function, and injury status. A novel SSTR2+ pericyte state correlated with disease severity and was reflected in lavage fluid by increased levels of the complement regulatory factor CFHR1. We further discovered CRTAC1 as a biomarker of alveolar type‐2 epithelial cell health status in lavage fluid and plasma. Using cross‐modal analysis and machine learning, we identified the cellular source of biomarkers and demonstrated that information transfer between modalities correctly predicts disease status, suggesting feasibility of clinical cell state monitoring through longitudinal sampling of body fluid proteomes.