Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic Factors Influencing Survival and a Treatment Pattern Analysis of Conventional Palliative Radiotherapy for Patients with Bone Metastases

Background: Treatment indication for bone metastases is influenced by patient prognosis. Single-fraction radiotherapy (SFRT) was proven equally effective as multiple fractionation regimens (MFRT) but continues to be underused. Objective: Primary objectives: (a) to identify prognostic factors for overall survival and (b) to analyze treatment patterns of palliative radiotherapy (proportion of SFRT indication and predictive factors of radiotherapy regimen) for bone metastases. Methods: 582 patients with bone metastases who underwent conventional radiotherapy between January 1st 2014–31 December 2017 were analyzed. The Cox proportional hazard model was used to identify predictors of overall survival. For the treatment pattern analysis, 677 radiotherapy courses were evaluated. The logistic regression model was used to identify potential predictors of radiotherapy regimen. Results: The 3-year overall survival was 15%. Prognostic factors associated with poor overall survival were multiple bone metastases [hazard ratio (HR = 5.4)], poor performance status (HR = 1.5) and brain metastases (HR = 1.37). SFRT prescription increased from 41% in 2017 to 51% in 2017. Predictors of SFRT prescription were a poor performance status [odds ratio (OR = 0.55)], lung (OR = 0.49) and urologic primaries (OR = 0.33) and the half-body lower site of irradiation (OR = 0.59). Spinal metastases were more likely to receive MFRT (OR = 2.09). Conclusions: Based on the prognostic factors we identified, a selection protocol for patients candidates for palliative radiotherapy to bone metastases could be established, in order to further increase SFRT prescription in our institution.
Tissue-Engineered Vascular Graft with Co-Culture of Smooth Muscle Cells and Human Endothelial Vein Cells on an Electrospun Poly(lactic-co-glycolic acid) Microtube Array Membrane

Coronary artery disease is one of the major diseases that plagues today’s modern society. Conventional treatments utilize synthetic vascular grafts such as Dacron® and Teflon® in bypass graft surgery. Despite the wide adaptation, these synthetic grafts are often plagued with weaknesses such as low hemocompatibility, thrombosis, intimal hyperplasia, and risks of graft infection. More importantly, these synthetic grafts are not available at diameters of less than 6 mm. In view of these challenges, we strived to develop and adapt the electrospun Poly Lactic-co-Glycolic Acid (PLGA) Microtube Array Membrane (MTAM) vascular graft for applications smaller than 6 mm in diameter. Homogenously porous PLGA MTAMs were successfully electrospun at 5.5–8.5 kV under ambient conditions. Mechanically, the PLGA MTAMs registered a maximum tensile strength of 5.57 ± 0.85 MPa and Young’s modulus value of 1.134 ± 0.01 MPa; while MTT assay revealed that seven-day Smooth Muscle Cells (SMCs) and Human Umbilical Vein Endothelial Cells (HUVECs) registered a 6 times and 2.4 times higher cell viability when cultured in a co-culture setting in medium containing α-1 haptaglobulin. When rolled into a vascular graft, the PLGA MTAMs registered an overall degradation of 82% after 60 days of cell co-culture. After eight weeks of culturing, immunohistochemistry staining revealed the formation of a monolayer of HUVECs with tight junctions on the surface of the PLGA MTAM, and as for the SMCs housed within the lumens of the PLGA MTAMs, a monolayer with high degree of orientation was observed. The PLGA MTAM registered a burst pressure of 1092.2 ± 175.3 mmHg, which was sufficient for applications such as small diameter blood vessels. Potentially, the PLGA MTAM could be used as a suitable substrate for vascular engineering.
Valorization of the Red Algae Gelidium sesquipedale by Extracting a Broad Spectrum of Minor Compounds Using Green Approaches

Until now, the red algae Gelidium sesquipedale has been primarily exploited for agar production, leaving an undervalued biomass. In this work, the use of eco-friendly approaches employing ultrasound-assisted extraction (UAE) and green solvents was investigated to valorize the algal minor compounds. The green methods used herein showed an attractive alternative to efficiently extract a broad spectrum of bioactive compounds in short extraction times (15 to 30 min vs. 8 h of the conventional method). Using the best UAE conditions, red seaweed extracts were characterized in terms of total phenolics (189.3 ± 11.7 mg GAE/100 g dw), flavonoids (310.7 ± 9.7 mg QE/100 g dw), mycosporine-like amino acids (MAAs) (Σ MAAs = 1271 mg/100 g dw), and phycobiliproteins (72.4 ± 0.5 mg/100 g dw). Additionally, produced algal extracts exhibited interesting antioxidant and anti-enzymatic activities for potential applications in medical and/or cosmetic products. Thus, this study provides the basis to reach a superior valorization of algal biomass by using alternative methods to extract biologically active compounds following eco-friendly approaches. Moreover, the strategies developed not only open new possibilities for the commercial use of Gelidium sesquipedale, but also for the valorization of different algae species since the techniques established can be easily adapted.
Evaluation of Bioactive Metabolites and Antioxidant-Rich Extracts of Amaranths with Possible Role in Pancreatic Lipase Interaction: In Silico and In Vitro Studies

Fat/carbohydrate-rich diet consumption or elevated secretion of pancreatic lipase (PL) in pancreatic injury results in increased fat digestion and storage. Several metabolites in plant-based diets can help achieve the requirements of nutrition and fitness together. Presently, nutritional metabolites from Amaranthus tricolor, A. viridis, and Achyranthes aspera were assessed and predicted for daily intake. The volatile-metabolite profiling of their extracts using GC-MS revealed various antioxidant and bioactive components. The implication of these specialized components and antioxidant-rich extracts (EC50 free radical scavenging: 34.1 ± 1.5 to 166.3 ± 14.2 µg/mL; FRAP values: 12.1 ± 1.0 to 34.0 ± 2.0 µg Trolox Equivalent/mg) in lipolysis regulation by means of interaction with PL was checked by in silico docking (Betahistine and vitamins: ΔGbind −2.3 to −4.4 kcal/mol) and in vitro fluorescence quenching. Out of the various compounds and extracts tested, Betahistine, ATRA and AVLA showed better quenching the PL fluorescence. The identification of potential extracts as source of functional components contributing to nutrition and fat regulation can be improved through such study.
Early Exposure and Its Impact on Cardiothoracic Surgery: an Experience of Medical Education in The United Kingdom

Introduction Cardiothoracic surgery (CTS) has seen a decline in interest and application rates in recent years. As a relatively small speciality, teaching and placements in CTS are often not included during undergraduate study and postgraduate training. We aim to evaluate the exposure to CTS during both undergraduate study and postgraduate training. Methods A ten-question online survey was designed and delivered to Foundation Year Two (FY2) doctors who graduated in 2017 and completed their two-year postgraduate foundation training in 2019. Medical schools with no graduates in 2017 and 2018 were excluded from our study. IBM® SPSS Statistics, version 25, and Microsoft Excel 365® were used for Student’s t-test statistical analysis. Results Three hundred and six FY2 doctors across 16 medical schools completed the survey, none of which included compulsory CTS attachments as their undergraduate curriculum. Thirty-two respondents (10.5%) underwent CTS attachments lasting between one to three weeks. Only 14 (43.8%) had worked in a cardiothoracic unit during their two-year Foundation Programme; 10 of which (71.2%) subsequently made an application for cardiothoracic speciality training. Most of the participants with previous exposure to CTS, during either undergraduate study or postgraduate Foundation Programme training or both, were significantly more likely to make an application to CTS training (P<0.05). Conclusion Our study suggests that doctors with increased exposure to CTS during undergraduate study and postgraduate training are more likely to pursue a career in CTS. Targeted interventions at both stages may improve interests in CTS and the number of prospective applicants.
Genetic structure of the protist Physarum albescens (Amoebozoa) revealed by multiple markers and genotyping by sequencing

Myxomycetes are terrestrial protists with many presumably cosmopolitan species dispersing via airborne spores. A truly cosmopolitan species would suffer from outbreeding depression hampering local adaptation, while locally adapted species with limited distribution would be at a higher risk of extinction in changing environments. Here, we investigate intraspecific genetic diversity and phylogeography of Physarum albescens over the entire Northern Hemisphere. We sequenced 324 field collections of fruit bodies for 1–3 genetic markers (SSU, EF1A, COI) and analysed 98 specimens with genotyping by sequencing. The structure of the three‐gene phylogeny, SNP‐based phylogeny, phylogenetic networks, and the observed recombination pattern of three independently inherited gene markers can be best explained by the presence of at least 18 reproductively isolated groups, which can be seen as cryptic species. In all intensively sampled regions and in many localities, members of several phylogroups coexisted. Some phylogroups were found to be abundant in only one region and completely absent in other well‐studied regions, and thus may represent regional endemics. Our results demonstrate that the widely distributed myxomycete species Ph. albescens represents a complex of at least 18 cryptic species, and some of these seem to have a limited geographical distribution. In addition, the presence of groups of presumably clonal specimens suggests that sexual and asexual reproduction coexist in natural populations of myxomycetes.
Restoration experiments in polymetallic nodule areas

Deep‐seabed polymetallic nodule mining can have multiple adverse effects on benthic communities, such as permanent loss of habitat by removal of nodules and habitat modification of sediments. One tool to manage biodiversity risks is the mitigation hierarchy, including avoidance, minimization of impacts, rehabilitation and/or restoration, and offset. We initiated long‐term restoration experiments at sites in polymetallic nodule exploration contract areas in the Clarion‐Clipperton Zone that were (i) cleared of nodules by a preprototype mining vehicle, (ii) disturbed by dredge or sledge, (iii) undisturbed, and (iv) naturally devoid of nodules. To accommodate for habitat loss, we deployed >2000 artificial ceramic nodules to study the possible effect of substrate provision on the recovery of biota and its impact on sediment biogeochemistry. Seventy‐five nodules were recovered after eight weeks and had not been colonized by any sessile epifauna. All other nodules will remain on the seafloor for several years before recovery. Furthermore, to account for habitat modification of the top sediment layer, sediment in an epibenthic sledge track was loosened by a metal rake to test the feasibility of sediment decompaction to facilitate soft‐sediment recovery. Analyses of granulometry and nutrients one month after sediment decompaction revealed that sand fractions are proportionally lower within the decompacted samples, whereas total organic carbon values are higher. Considering the slow natural recovery rates of deep‐sea communities, these experiments represent the beginning of a ~30‐year study during which we expect to gain insights into the nature and timing of the development of hard‐substrate communities and the influence of nodules on the recovery of disturbed sediment communities. Results will help us understand adverse long‐term effects of nodule removal, providing an evidence base for setting criteria for the definition of “serious harm” to the environment. Furthermore, accompanying research is needed to define a robust ecosystem baseline in order to effectively identify restoration success. Integr Environ Assess Manag 2022;18:682–696. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Camrelizumab for relapsed or refractory classical Hodgkin lymphoma: Extended follow‐up of the multicenter, single‐arm, Phase 2 study

Camrelizumab (a humanized high‐affinity IgG4 mAb against programmed death‐l) showed potent antitumor activity, well tolerance and controllable safety in patients with relapsed or refractory classical Hodgkin lymphoma (r/r cHL), based on the primary analysis of a Phase 2 study. Here, we present the extended follow‐up outcomes. Seventy‐five patients who had failed to achieve a remission or experienced progression after autologous stem cell transplantation or had received at least two lines of systemic chemotherapies were enrolled to receive camrelizumab 200 mg every 2 weeks. With a median follow‐up of 36.2 months (range, 7.2‐38.1), objective response rate per independent central review was 76.0% (95% confidence interval [CI], 64.7‐85.1). Among the 57 responders, 31 (54.4%) had ongoing responses. Median duration of response was 31.7 months (95% CI, 16.7‐not reached). Median progression‐free survival was 22.5 months (95% CI, 14.7‐not reached). Thirty‐six‐month overall survival rate was 82.7% (95% CI, 72.0‐89.5). Reactive capillary endothelial proliferation (RCEP) occurred in 97.3% of patients (73/75), but all RCEP were Grade 1 or 2 in severity and 67.1% of these patients (49/73) achieved complete resolution. Occurrence of new RCEP lesions was rare (8/42 [19.0%] at 12 months; 2/32 [6.3%] at 24 months). No treatment‐related deaths occurred, and no new toxicities were reported. With extended follow‐up, camrelizumab monotherapy continues to provide a robust and durable response, long survival and manageable safety in r/r cHL patients.
Work‐relatedness of lateral epicondylitis: Systematic review including meta‐analysis and GRADE work‐relatedness of lateral epicondylitis

Abstract Background Lateral epicondylitis (LE) is a highly prevalent musculoskeletal disorder in workers, often associated with physically demanding work. Knowledge of work‐relatedness of LE is crucial to develop appropriate preventive measures. This study investigates the prospective association between work‐related physical risk factors and LE. Methods A systematic literature review was conducted in MedLine using PubMed from January 1, 2010 until February 16, 2021. Published reports were included if: (1) LE was clinically assessed, (2) exposure to work‐related physical risk factors was assessed, and (3) associations between LE and work‐related physical risk factors were reported in prospective studies. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation. Results In total, 318 workers with LE from a population of 5036 workers in five studies were included. Meta‐analyses revealed high‐quality evidence for associations between LE and a Strain Index (SI) score >5.1 (odds ratio [OR]: 1.75, 95% confidence interval (CI): 1.11–2.78) and moderate‐quality evidence for forearm rotation >4 h/day or forearm rotation ≥45° for ≥45% time (OR: 1.85, 95% CI: 1.10–3.10). Gripping, flexion and extension of the wrist, and repetitive movements showed no significant associations with LE. Conclusion High‐quality evidence was found indicating that a higher SI increased the risk of LE. Moderate‐quality evidence was found for an association between forearm rotation and LE. No associations were found between other physical risk factors and LE. Primary preventive interventions should focus on a reduction of the SI and of high forearm rotation in work.
Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target

Apolipoprotein (apo) B, the critical structural protein of the atherogenic lipoproteins, has two major isoforms: apoB48 and apoB100. ApoB48 is found in chylomicrons and chylomicron remnants with one apoB48 molecule per chylomicron particle. Similarly, a single apoB100 molecule is contained per particle of very-low-density lipoprotein (VLDL), intermediate density lipoprotein, LDL and lipoprotein(a). This unique one apoB per particle ratio makes plasma apoB concentration a direct measure of the number of circulating atherogenic lipoproteins. ApoB levels indicate the atherogenic particle concentration independent of the particle cholesterol content, which is variable. While LDL, the major cholesterol-carrying serum lipoprotein, is the primary therapeutic target for management and prevention of atherosclerotic cardiovascular disease, there is strong evidence that apoB is a more accurate indicator of cardiovascular risk than either total cholesterol or LDL cholesterol. This review examines multiple aspects of apoB structure and function, with a focus on the controversy over use of apoB as a therapeutic target in clinical practice. Ongoing coronary artery disease residual risk, despite lipid-lowering treatment, has left patients and clinicians with unsatisfactory options for monitoring cardiovascular health. At the present time, the substitution of apoB for LDL-C in cardiovascular disease prevention guidelines has been deemed unjustified, but discussions continue.
Marek’s disease virus prolongs survival of primary chicken B-cells by inducing a senescence-like phenotype

Marek’s disease virus (MDV) is an alphaherpesvirus that causes immunosuppression and deadly lymphoma in chickens. Lymphoid organs play a central role in MDV infection in animals. B-cells in the bursa of Fabricius facilitate high levels of MDV replication and contribute to dissemination at early stages of infection. Several studies investigated host responses in bursal tissue of MDV-infected chickens; however, the cellular responses specifically in bursal B-cells has never been investigated. We took advantage of our recently established in vitro infection system to decipher the cellular responses of bursal B-cells to infection with a very virulent MDV strain. Here, we demonstrate that MDV infection extends the survival of bursal B-cells in culture. Microarray analyses revealed that most cytokine/cytokine-receptor-, cell cycle- and apoptosis-associated genes are significantly down-regulated in these cells. Further functional assays validated these strong effects of MDV infections on cell cycle progression and thus, B-cell proliferation. In addition, we confirmed that MDV infections protect B-cells from apoptosis and trigger an accumulation of the autophagy marker Lc3-II. Taken together, our data indicate that MDV-infected bursal B-cells show hallmarks of a senescence-like phenotype, leading to a prolonged B-cell survival. This study provides an in-depth analysis of bursal B-cell responses to MDV infection and important insights into how the virus extends the survival of these cells.
Dietary ω-3 polyunsaturated fatty acids are protective for myopia

Significance Myopia is a leading cause of visual impairment. However, a safe and accessible approach for myopia control is currently unavailable. In the present study, we demonstrated that dietary supplements of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) attenuated myopia development in animal models. ω-3 PUFAs also ameliorated near-work–induced decreases in choroidal blood perfusion in young adults. Hence, when safety and effectiveness have been confirmed in future clinical studies, ω-3 PUFAs should be attractive candidates for myopia control in humans. Myopia is a leading cause of visual impairment and blindness worldwide. However, a safe and accessible approach for myopia control and prevention is currently unavailable. Here, we investigated the therapeutic effect of dietary supplements of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on myopia progression in animal models and on decreases in choroidal blood perfusion (ChBP) caused by near work, a risk factor for myopia in young adults. We demonstrated that daily gavage of ω-3 PUFAs (300 mg docosahexaenoic acid [DHA] plus 60 mg eicosapentaenoic acid [EPA]) significantly attenuated the development of form deprivation myopia in guinea pigs and mice, as well as of lens-induced myopia in guinea pigs. Peribulbar injections of DHA also inhibited myopia progression in form-deprived guinea pigs. The suppression of myopia in guinea pigs was accompanied by inhibition of the “ChBP reduction–scleral hypoxia cascade. ” Additionally, treatment with DHA or EPA antagonized hypoxia-induced myofibroblast transdifferentiation in cultured human scleral fibroblasts. In human subjects, oral administration of ω-3 PUFAs partially alleviated the near-work–induced decreases in ChBP. Therefore, evidence from these animal and human studies suggests ω-3 PUFAs are potential and readily available candidates for myopia control.
Associations of 12‐year sleep behaviour trajectories from childhood to adolescence with myopia and ocular biometry during young adulthood

Cross‐sectional studies have variably reported that poor sleep quality may be associated with myopia in children. Longitudinal data, collected over the ages when myopia develops and progresses, could provide new insights into the sleep‐myopia paradigm. This study tested the hypothesis that 12‐year trajectories of sleep behaviour from childhood to adolescence is associated with myopia during young adulthood.
Enhanced Antitumor Responses of Tumor Antigen-Specific TCR T Cells Genetically Engineered to Produce IL7 and CCL19

Although adoptive transfer of T cells genetically engineered to express chimeric antigen receptor (CAR) or T-cell receptor (TCR) has been actively developed and applied into clinic recently, further improvement of these modalities is highly demanded, especially in terms of its efficacy. Because we previously revealed the profound enhancement of antitumor effects of CAR T cells by concomitant expression of IL7 and CCL19, this study further explored a potential of IL7/CCL19 production technology to augment antitumor effects of TCR T cells. IL7/CCL19-producing P1A tumor antigen-specific TCR T cells (7 × 19 P1A T cells) demonstrated significantly improved antitumor effects, compared with those without IL7/CCL19 production, and generated long-term memory responses. The antitumor effects of 7×19 P1A T cells were further upregulated by combination with anti–PD-1 antibody, in which blockade of PD-1 signal in both 7×19 P1A T cells and endogenous T cells plays an important role. Taken together, our study demonstrated that concomitant production of IL7 and CCL19 by genetically engineered tumor-reactive T cells could synergize with PD-1 blockade therapy to generate potent and long-lasting antitumor immunity.
Leptospiral meningoencephalitis in a raccoon dog

Neuroleptospirosis is a rare disease caused by pathogenic Leptospira interrogans in humans; however, it has not been fully studied in animals. A young wild raccoon dog was found convulsing in the recumbent position and died the next day. Histologic examination revealed nonsuppurative meningoencephalitis in the cerebrum, cerebellum, midbrain, and medulla oblongata. The lesions consisted of mixed infiltrates of Iba1-positive macrophages and CD3-positive T cells, with a small number of CD79α-positive B cells and myeloperoxidase-positive neutrophils. In the frontal cortex, perivascular cuffs and adjacent microglial nodules were distributed diffusely, especially in the molecular layer. Glial nodules were comprised of Iba1- and myeloperoxidase-positive activated microglia. Immunohistochemistry revealed leptospires in mononuclear cell perivascular cuffs, but not in glial nodules. Neuroleptospirosis was accompanied by Leptospira-related nonsuppurative interstitial nephritis, pulmonary edema and hemorrhage, and coronary periarteritis, as well as Toxocara tanuki in the small intestine and nonspecific foreign-body granulomas in the lungs and stomach.