Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of palliative chemotherapy near the end of life: a retrospective cohort study.

BACKGROUND For patients with metastatic cancer, treatment with palliative chemotherapy can lead to more aggressive end-of-life (EOL) care. This retrospective study aimed to assess the time from the last chemotherapy treatment to death and investigate the variables associated with the delivery of palliative chemotherapy near the end of life. METHODS Data from patients who died from metastatic cancer after receiving palliative chemotherapy from April 2007 to June 2019 at the Department of Integrated Therapy of Fudan University, Shanghai Cancer Center were analyzed. Statistical analysis was performed to evaluate variables including the patient's age, Charlson comorbidities, caregivers, and the type of cancer. RESULTS A total of 605 patients were included in the analysis, of whom 335 (58.7%) were treated with palliative chemotherapy during their last year of life and 16.2% were treated in their last month of life. Treatment with palliative chemotherapy in the last month was independently associated with age (P<0.001). In the last year of life, treatment with palliative chemotherapy differed significantly according to caregivers and age (P<0.001). The interval between the last chemotherapy treatment and death was the shortest for patients whose caregivers were adult children or those aged ≤50 years. CONCLUSIONS In this study, palliative chemotherapy was used to treat 58.7% of patients in their last year, and 16.2% of patients in their last month, which is in line with international recommendations. In the last month, palliative chemotherapy was independently associated with age (P<0.001), whereas patients were more likely to receive palliative chemotherapy in their last year if their caregivers were adult children or if they were aged ≤50 years. Significant variations in EOL treatment strategies were observed according to caregivers and patient age during the last year of life.
The effect of pH on staining of oospores of Peronospora viciae with tetrazolium bromide.

Tetrazolium bromide was tested as a vital stain for oospores of Peronospora viciae f. sp.fabae and P. viciae f. sp. pisi in phosphate buffers with a pH ranging from 6.0 to 8.0. Oospores stained mostly pink to red, seldom black. The number of black oospores increased with incubation time but the total number of pink, red and black oospores did not increase. The results suggest overstaining as the cause of black oo? spores. The number of stained, nonautoclaved oo? spores showed a small increase at higher pH. The pH had a large effect on staining of oospores killed by autoclaving. Similar numbers of autoclaved and non? autoclaved oospores stained at pH 7.5 and 8.0, but few autoclaved oospores stained at pH lower than 7.0. When using tetrazolium bromide (0.1% solution) as a vital stain for oospores of Peronospora viciae, good staining results are obtained with a 48-h incubation at 35 C in solutions at pH 6.0 to 6.5.
Satisfaction with antipsychotics as a medication: the role of therapeutic alliance and patient-perceived participation in decision making in patients with schizophrenia spectrum disorder

Abstract Objectives The aim of this study was to identify independent predictors of satisfaction with antipsychotics in patients with schizophrenia spectrum disorders treated in a mental health catchment area. Methods Observational analytical study of patients (n = 150) recruited through a convenience sampling method from five mental health units. Satisfaction with the antipsychotic as a medication was evaluated using the Treatment Satisfaction Questionnaire for Medication (TSQM). Therapeutic alliance was assessed by the Working Alliance Inventory Short Form (WAI-S). Patient-perceived participation in decision-making was assessed using COMRADE (Combined Outcome Measure for Risk communication And treatment Decision making Effectiveness). A multiple linear regression analysis was performed to identify variables independently associated with the TSQM ‘Global Satisfaction’ total score. Results Two variables – age and higher level of self-perceived participation in treatment decision-making – were directly, significantly, and independently associated (β coefficient values: 0.209 and 0.432, respectively) with a higher TSQM Global satisfaction score. In addition, the severity of psychotic symptoms was inversely associated with satisfaction (β coefficient value: −0.205) (R 2 = 0.355; R 2 adj. = 0.291; F(13) = 5.554; p < 0.01). Conclusions These findings suggest that involving the patient in treatment decision-making and optimising the treatment to reduce symptoms, especially in younger patients, could increase satisfaction with antipsychotic treatment. Key Points Patient involvement in shared decision-making is relevant for treatment satisfaction. Current evidence suggests that improving the doctor–patient relationship optimises antipsychotics outcomes. Self-perceived participation in decision-making predicts satisfaction with antipsychotic medication. Types of antipsychotics do not determine consistent differences in satisfaction.
Modulation and Protection Effects of Antioxidant Compounds against Oxidant Induced Developmental Toxicity in Zebrafish

The antioxidant effect of compounds is regularly evaluated by in vitro assays that do not have the capability to predict in vivo protective activity or to determine their underlying mechanisms of action. The aim of this study was to develop an experimental system to evaluate the in vivo protective effects of different antioxidant compounds, based on the zebrafish embryo test. Zebrafish embryos were exposed to tert-butyl hydroperoxide (tBOOH), tetrachlorohydroquinone (TCHQ) and lipopolysaccharides from Escherichia coli (LPS), chemicals that are known inducers of oxidative stress in zebrafish. The developmental toxic effects (lethality or dysmorphogenesis) induced by these chemicals were modulated with n-acetyl l-cysteine and Nω-nitro l-arginine methyl ester hydrochloride, dimethyl maleate and dl-buthionine sulfoximine in order to validate the oxidant mechanism of oxidative stress inducers. The oxidant effects of tBOOH, TCHQ, and LPS were confirmed by the determination of significant differences in the comparison between the concentration–response curves of the oxidative stress inducers and of the modulators of antioxidant status. This concept was also applied to the study of the effects of well-known antioxidants, such as vitamin E, quercetin, and lipoic acid. Our results confirm the zebrafish model as an in vivo useful tool to test the protective effects of antioxidant compounds.
Total sulphur contents of epiphytic and terricolous lichens in Finland

The sulphur content was studied in the epiphytic lichens Hypogymnia physodes (L.) Nyl. and Pseudevernia furfuracea (L.) Zopf, in the terricolous lichens Cladonia sp. and Pehigera aphthosa (L.) Willd. (inch some Nephroma arcticum (L.) Torss. ), and also in pine and birch bark and in the layer below the birch bark in 31 sites in Finland. Sulphur was determined by the isotope excited X-ray fluorescence method, using a semiconductor detector. The total sulphur content of the lichens appeared to depend closely upon the species and to vary considerably due to several factors. In H. physodes and P. furfuracea it had a highly significant correlation with the wet and dry sulphate deposition. In P. aphthosa (and N. arcticum) the sulphur content also correlated with the sulphate deposition. In Cladonia, however, there was no correlation between the sulphur content and the sulphate deposition, which indicates that the sulphur uptake mechanism is different in this lichen. The sulphur contents of H. physodes and P. furfuracea in different parts of Finland showed statistically significant regional variation. The microclimatic factors were considered, account being taken of the sources and chemical form of the sulphur, and the phorophyte species and their habitats.
An Update on Molecular Tools for Genetic Engineering of Actinomycetes—The Source of Important Antibiotics and Other Valuable Compounds

The first antibiotic-producing actinomycete (Streptomyces antibioticus) was described by Waksman and Woodruff in 1940. This discovery initiated the “actinomycetes era”, in which several species were identified and demonstrated to be a great source of bioactive compounds. However, the remarkable group of microorganisms and their potential for the production of bioactive agents were only partially exploited. This is caused by the fact that the growth of many actinomycetes cannot be reproduced on artificial media at laboratory conditions. In addition, sequencing, genome mining and bioactivity screening disclosed that numerous biosynthetic gene clusters (BGCs), encoded in actinomycetes genomes are not expressed and thus, the respective potential products remain uncharacterized. Therefore, a lot of effort was put into the development of technologies that facilitate the access to actinomycetes genomes and activation of their biosynthetic pathways. In this review, we mainly focus on molecular tools and methods for genetic engineering of actinomycetes that have emerged in the field in the past five years (2015–2020). In addition, we highlight examples of successful application of the recently developed technologies in genetic engineering of actinomycetes for activation and/or improvement of the biosynthesis of secondary metabolites.
Physiological and functional responses of water-cooled versus traditional radiofrequency ablation of peripheral nerves in rats

Background and objectives Several clinical studies have focused on assessing the effectiveness of different radiofrequency ablation (RFA) modalities in pain management. While a direct head-to-head clinical study is needed, results from independent studies suggest that water-cooled RFA (CRFA) may result in longer lasting pain relief than traditional RFA (TRFA). The primary purpose of this study was, therefore, to investigate in a preclinical model, head-to-head differences between the two RFA technologies. Methods RFA was performed in a rat sciatic nerve model (n=66) in two groups: (1) TRFA or (2) CRFA. The surgeon was not blinded to the treatment; however, all the physiological endpoints were assessed in a blinded fashion which include histological, MRI, and nerve function assessment via electromyography. Results The energy delivered by the generator for CRFA was significantly higher compared with TRFA. Histological staining of nerves harvested immediately following CRFA exhibited extended length and multiple zones of thermal damage compared with TRFA-treated nerves. MRI scans across 4 weeks following treatment showed edematous/inflammatory zones present for longer times following CRFA. Finally, there was greater attenuation and prolonged loss of nerve function measured via electromyography in the CRFA group. Conclusions This study shows that CRFA has greater energy output, as well as more pronounced structural and functional changes elicited on the peripheral nerves compared with TRFA. While these preclinical data will need to be confirmed with a large clinical randomized controlled trial, we are encouraged by the direction that they may have set for those trials.
THE LATERAL LINE SYSTEM OF TWO SYMPATRIC EASTERN PACIFIC GOBIID FISHES OF THE GENUS LYTHRYPNUS (TELEOSTEI: GOBIIDAE)

Lythrypnus dalli (Gilbert, 1890) and Lythrypnus zebra (Gilbert, 1890) occur sympatrically in rocky subtidal habitats of the eastern Pacific, but occupy distinct microhabitats. The two species belong to different species complexes. We were interested if the differences in microhabitat use of these two gobiids correspond to differences in the pattern of the lateral line system, which is represented by relatively few and large free neuromasts. The neuromast pattern is similar in both gobies with few, but characteristic differences. These differences also occur among other species of the two species complexes (i.e., Lythrypnus cobalus and Lythrypnus gilberti of the Lythrypnus dalli complex and Lythrypnus pulchellus and Lythrypnus rhizophora of the Lythrypnus rhizophora complex) and support the recognition of east Pacific species in two species complexes. The topography of the free neuromasts and their innervation is described for Lythrypnus dalli and Lythrypnus zebra.
Current Imaging Trends in COVID-19 Pneumonia

ABSTRACT COVID-19 has rapidly emerged as a pandemic threatening lives and healthcare systems worldwide. With the emergence of the disease in Nepal, all faculties of medicine need to be well prepared to face the challenge. Fortunately, now plenty of research is available to facilitate our preparedness in the war against COVID-19. The reverse transcriptase-polymerase chain reaction is the current gold standard diagnostic test and chest Computed Tomography scan for screening the disease is considered inappropriate by most society recommendations. The Nepal Radiologists’ Association has proposed its guidelines which have been endorsed by the Nepal Medical Council. This article aims to summarize the role of imaging focusing on chest X-ray and Computed Tomography scan including the indications, specific findings, and important differentials. Imaging needs to be done taking necessary precautions, to minimize disease transmission, protect health care personnel, and preserve health care system functioning.
Online Guide for Electronic Health Evaluation Approaches: Systematic Scoping Review and Concept Mapping Study

Background Despite the increase in use and high expectations of digital health solutions, scientific evidence about the effectiveness of electronic health (eHealth) and other aspects such as usability and accuracy is lagging behind. eHealth solutions are complex interventions, which require a wide array of evaluation approaches that are capable of answering the many different questions that arise during the consecutive study phases of eHealth development and implementation. However, evaluators seem to struggle in choosing suitable evaluation approaches in relation to a specific study phase. Objective The objective of this project was to provide a structured overview of the existing eHealth evaluation approaches, with the aim of assisting eHealth evaluators in selecting a suitable approach for evaluating their eHealth solution at a specific evaluation study phase. Methods Three consecutive steps were followed. Step 1 was a systematic scoping review, summarizing existing eHealth evaluation approaches. Step 2 was a concept mapping study asking eHealth researchers about approaches for evaluating eHealth. In step 3, the results of step 1 and 2 were used to develop an “eHealth evaluation cycle” and subsequently compose the online “eHealth methodology guide. ” Results The scoping review yielded 57 articles describing 50 unique evaluation approaches. The concept mapping study questioned 43 eHealth researchers, resulting in 48 unique approaches. After removing duplicates, 75 unique evaluation approaches remained. Thereafter, an “eHealth evaluation cycle” was developed, consisting of six evaluation study phases: conceptual and planning, design, development and usability, pilot (feasibility), effectiveness (impact), uptake (implementation), and all phases. Finally, the “eHealth methodology guide” was composed by assigning the 75 evaluation approaches to the specific study phases of the “eHealth evaluation cycle. ” Conclusions Seventy-five unique evaluation approaches were found in the literature and suggested by eHealth researchers, which served as content for the online “eHealth methodology guide. ” By assisting evaluators in selecting a suitable evaluation approach in relation to a specific study phase of the “eHealth evaluation cycle,” the guide aims to enhance the quality, safety, and successful long-term implementation of novel eHealth solutions.
Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19

Coronavirus disease 2019 (COVID-19) infection causes acute lung injury, resulting from aggressive inflammation initiated by viral replication. There has been much speculation about the potential role of non-steroidal inflammatory drugs (NSAIDs), which increase the expression of angiotensin-converting enzyme 2 (ACE2), a binding target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the host cell, which could lead to poorer outcomes in COVID-19 disease. The aim of this study was to examine the association between routine use of NSAIDs and outcomes in hospitalised patients with COVID-19. This was a multicentre, observational study, with data collected from adult patients with COVID-19 admitted to eight UK hospitals. Of 1222 patients eligible to be included, 54 (4.4%) were routinely prescribed NSAIDs prior to admission. Univariate results suggested a modest protective effect from the use of NSAIDs, but in the multivariable analysis, there was no association between prior NSAID use and time to mortality (adjusted HR (aHR) = 0.89, 95% CI 0.52–1.53, p = 0.67) or length of stay (aHR 0.89, 95% CI 0.59–1.35, p = 0.58). This study found no evidence that routine NSAID use was associated with higher COVID-19 mortality in hospitalised patients; therefore, patients should be advised to continue taking these medications until further evidence emerges. Our findings suggest that NSAID use might confer a modest benefit with regard to survival. However, as this finding was underpowered, further research is required.
Comprehensive Prediction of Molecular Recognition in a Combinatorial Chemical Space using Machine Learning.

In combinatorial chemical approaches, optimizing the composition and arrangement of building blocks towards a partic-ular function has been done using a number of methods, including high throughput molecular screening, molecular evolu-tion and computational prescreening. Here, a different approach is considered that uses sparse measurements of library molecules as the input to a machine learning algorithm which generates a comprehensive, quantitative relationship be-tween covalent molecular structure and function that can then be used to predict the function of any molecule in the pos-sible combinatorial space. To test the feasibility of the approach, a defined combinatorial chemical space consisting of ~1012 possible linear combinations of 16 different amino acids was used. The binding of a very sparse, but nearly ran-dom, sampling of this amino acid sequence space to 9 different protein targets is measured and used to generate a general relationship between peptide sequence and binding for each target. Surprisingly, measuring as little as a few hundred to a few thousand of the ~1012 possible molecules provides sufficient training to be highly predictive of the binding of the remaining molecules in the combinatorial space. Further, measuring only amino acid sequences that bind weakly to a target allows the accurate prediction of which sequences will bind 10-100 times more strongly. Thus, the molecular recognition information contained in a tiny fraction of molecules in this combinatorial space is sufficient to characterize any set of molecules randomly selected from the entire space, a fact that potentially has significant implications for the design of new chemical function using combinatorial chemical libraries.
Specific key-point mutations along the helical conformation of Huntingtin-Exon 1 protein might have an antagonistic effect on the toxic helical content's formation.

The polyglutamine tract's length represents a key regulator for Huntington's disease toxicity level and its aggregation rates, often being related to helical structural conformations. In this study we performed all-atom MD simulations on mutant Huntingtin-Exon1 protein with additional mutation spots, aiming to observe the corresponding structural and dynamical changes at the level of the helix. The simulated structures consist of three sets of Q residue mutations into P residues (4P, 7P and 9P), each set including different spots of mutations: random along the mutant sequence (R models), at the edges of the helix (E models), as well as at the edges and in the middle of the helix (EM models). At the helical level, our results predict less compactness profiles for higher number of P mutations (7P and 9P models) with particular mutation spots at the edges and at the edges-middle of the helix. Moreover, the C-alpha atoms distances decreased for 7P and 9P models in comparison to 4P models and the RMSF values show highest fluctuation rates for 9P models with point mutations at the edges and in the middle of the helix. The secondary structure analysis suggest greater structural transitions from α-helices to bends, turns and random coils for 7P and 9P models, particularly for point mutations considered at the edges and in the middle of the helical content. The obtained results support our hypothesis that specific key-point mutations along the helical conformation might have an antagonistic effect on the toxic helical content's formation.
Association between tissue hypoxia, perfusion restrictions, and microvascular architecture alterations with lesion-induced impairment of neurovascular coupling

Functional magnetic resonance imaging (fMRI) has been mainly utilized for the preoperative localization of eloquent cortical areas. However, lesion-induced impairment of neurovascular coupling (NVC) in the lesion border zone may lead to false-negative fMRI results. The purpose of this study was to determine physiological factors impacting the NVC. Twenty patients suffering from brain lesions were preoperatively examined using multimodal neuroimaging including fMRI, magnetoencephalography (MEG) during language or sensorimotor tasks (depending on lesion location), and a novel physiologic MRI approach for the combined quantification of oxygen metabolism, perfusion state, and microvascular architecture. Congruence of brain activity patterns between fMRI and MEG were found in 13 patients. In contrast, we observed missing fMRI activity in perilesional cortex that demonstrated MEG activity in seven patients, which was interpreted as lesion-induced impairment of NVC. In these brain regions with impaired NVC, physiologic MRI revealed significant brain tissue hypoxia, as well as significantly decreased macro- and microvascular perfusion and microvascular architecture. We demonstrated that perilesional hypoxia with reduced vascular perfusion and architecture is associated with lesion-induced impairment of NVC. Our physiologic MRI approach is a clinically applicable method for preoperative risk assessment for the presence of false-negative fMRI results and may prevent severe postoperative functional deficits.
Curcumin/Usnic Acid-Loaded Electrospun Nanofibers Based on Hyaluronic Acid

Hyaluronic acid, curcumin, and usnic acid are separately utilized as effective biological agents in medicine, and materials based on its blend are considered to have wider therapeutic effects than individual ones. In this study, for the first time, native hyaluronic acid-based fibers containing curcumin and usnic acid with an average diameter of 298 nm were successfully prepared by the electrospinning technique and characterized. Additionally, unstable and hydrophobic curcumin and usnic acid were loaded into the hydrophilic hyaluronic acid matrix without utilizing the activating (catalyzing) agents, resulting in the formation of an electrospinnable solution. Only the binary mixture deionized water—dimethyl sulfoxide (50:50)—was used as solvent. The presence of small amounts of dimethyl sulfoxide in the fibrous materials was expected to provide the materials with local anesthetic and antiseptic activity. The effect of electric voltage on the electrospinning process, diameter, and morphology of hyaluronic acid/curcumin/usnic acid fibers was investigated in detail. The impact of curcumin and usnic acid on the stability of fiber formation was observed. The investigation of fibers based on pure hyaluronic acid without additional polymers and with active pharmaceutical ingredients will lay the groundwork for the development of highly effective wound dressings and new drug delivery scaffolds.