Miracle-dz/UniFAR-FTUs huggingface dataset:
A robust VMAT delivery solution for single‐fraction lung SABR utilizing FFF beams minimizing dosimetric compromise

Abstract Peripheral lung lesions treated with a single fraction of stereotactic ablative body radiotherapy (SABR) utilizing volumetric modulated arc therapy (VMAT) delivery and flattening filter‐free (FFF) beams represent a potentially high‐risk scenario for clinically significant dose blurring effects due to interplay between the respiratory motion of the lesion and dynamic multi‐leaf collimators (MLCs). The aim of this study was to determine an efficient means of developing low‐modulation VMAT plans in the Eclipse treatment planning system (v15.5, Varian Medical Systems, Palo Alto, USA) in order to minimize this risk, while maintaining dosimetric quality. The study involved 19 patients where an internal target volume (ITV) was contoured to encompass the entire range of tumor motion, and a planning target volume (PTV) created using a 5‐mm isotropic expansion of this contour. Each patient had seven plan variations created, with each rescaled to achieve the clinical planning goal for PTV coverage. All plan variations used the same field arrangement, and consisted of one dynamic conformal arc therapy (DCAT) plan, and six VMAT plans with varying degrees of modulation restriction, achieved through utilizing different combinations of the aperture shape controller (ASC) in the calculation parameters, and monitor unit (MU) objective during optimization. The dosimetric quality was assessed based on RTOG conformity indices (CI100/CI50), as well as adherence to dose–volume metrics used clinically at our institution. Plan complexity was assessed based on the modulation factor (MU/cGy) and the field edge metric. While VMAT plans with the least modulation restriction achieved the best dosimetry, it was found that there was no clinically significant trade‐off in terms of dose to organs at risk and conformity by reducing complexity. Furthermore, it was found that utilizing the ASC and MU objective could reduce plan complexity to near‐DCAT levels with improved dosimetry, which may be sufficiently robust to overcome the interplay effect.
Novel Anti-Hexokinase 1 Antibodies Are Associated With Poor Prognosis in Patients With Primary Biliary Cholangitis.

OBJECTIVES Antibodies to hexokinase 1 (HK1) and kelch-like 12 (KLHL12) have been identified as potential biomarkers in primary biliary cholangitis (PBC), and this study assesses changes of these antibodies over time and if they are associated with clinical outcomes. METHODS Two hundred fifty-four PBC patients (93.3% female, 51 ± 12.3 years old) were tested for anti-HK1 and anti-KLHL12, antimitochondrial (AMA), anti-gp210, and anti-sp100 antibodies. One hundred sixty-nine patients were tested twice and 49 three times within 4.2 (0.8-10.0) years. Biochemistry and clinical features at diagnosis, response to therapy, events of decompensation, and liver-related death or transplantation were evaluated. RESULTS Anti-HK1 and anti-KLHL2 were detected in 46.1% and 22.8% patients, respectively. AMA were positive in 93.7%, anti-sp100 in 26.4%, and anti-gp210 in 21.3% of patients. Anti-HK1 and anti-KLHL12 positivity changed over time in 13.3% and 5.5% of patients, respectively. Anti-HK1 or anti-KLHL12 were present in 37.5% of AMA-negative patients, and in 40% of AMA, anti-gp210, and anti-sp100 negative. No significant differences were observed between those with or without HK1 and KLHL12 antibodies, but transplant-free survival and time to liver decompensation were significantly lower in patients anti-HK1 positive (P = 0.039; P = 0.04) and in those anti-sp100 positive (P = 0.01; P = 0.007). No changes in survival and events of liver decompensation were observed according to the positivity of AMA, anti-KLHL12, or anti-gp210 antibodies. DISCUSSION HK1 and KLHL12 antibodies are present in 40% of PBC patients who are seronegative by the conventional PBC-specific antibodies. The novel antibodies remain rather steady during the course of the disease, and HK1 antibodies are associated with unfavourable outcomes.
Transdiagnostic and disease-specific abnormalities in the default-mode network hubs in psychiatric disorders: A meta-analysis of resting-state functional imaging studies

Abstract Background. The default mode network (DMN) dysfunction has emerged as a consistent biological correlate of multiple psychiatric disorders. Specifically, there is evidence of alterations in DMN cohesiveness in schizophrenia, mood and anxiety disorders. The aim of this study was to synthesize at a fine spatial resolution the intra-network functional connectivity of the DMN in adults diagnosed with schizophrenia, mood and anxiety disorders, capitalizing on powerful meta-analytic tools provided by activation likelihood estimation. Methods. Results from 70 whole-brain resting-state functional magnetic resonance imaging articles published during the last 15 years were included comprising observations from 2,789 patients and 3,002 healthy controls. Results. Specific regional changes in DMN cohesiveness located in the anteromedial and posteromedial cortex emerged as shared and trans-diagnostic brain phenotypes. Disease-specific dysconnectivity was also identified. Unmedicated patients showed more DMN functional alterations, highlighting the importance of interventions targeting the functional integration of the DMN. Conclusion. This study highlights functional alteration in the major hubs of the DMN, suggesting common abnormalities in self-referential mental activity across psychiatric disorders.
Scientific note. A scientific note on the natural merger of two honeybee colonies (Apis mellifera capensis)

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Scientific note. A scientific note on the natural merger of two honeybee colonies (Apis mellifera capensis) Peter Neumann, Christian Pirk, Randall Hepburn, Sarah Radloff
Delayed presentation of acute ischemic strokes during the COVID-19 crisis

Background The COVID-19 pandemic has disrupted established care paths worldwide. Patient awareness of the pandemic and executive limitations imposed on public life have changed the perception of when to seek care for acute conditions in some cases. We sought to study whether there is a delay in presentation for acute ischemic stroke patients in the first month of the pandemic in the US. Methods The interval between last-known-well (LKW) time and presentation of 710 consecutive patients presenting with acute ischemic strokes to 12 stroke centers across the US were extracted from a prospectively maintained quality database. We analyzed the timing and severity of the presentation in the baseline period from February to March 2019 and compared results with the timeframe of February and March 2020. Results There were 320 patients in the 2-month baseline period in 2019, there was a marked decrease in patients from February to March of 2020 (227 patients in February, and 163 patients in March). There was no difference in the severity of the presentation between groups and no difference in age between the baseline and the COVID period. The mean interval from LKW to the presentation was significantly longer in the COVID period (603±1035 min) compared with the baseline period (442±435 min, P<0.02). Conclusion We present data supporting an association between public awareness and limitations imposed on public life during the COVID-19 pandemic in the US and a delay in presentation for acute ischemic stroke patients to a stroke center.
A Study on Microstructure, Residual Stresses and Stress Corrosion Cracking of Repair Welding on 304 Stainless Steel: Part I-Effects of Heat Input

In this paper, the effect of repair welding heat input on microstructure, residual stresses, and stress corrosion cracking (SCC) sensitivity were investigated by simulation and experiment. The results show that heat input influences the microstructure, residual stresses, and SCC behavior. With the increase of heat input, both the δ-ferrite in weld and the average grain width decrease slightly, while the austenite grain size in the heat affected zone (HAZ) is slightly increased. The predicted repair welding residual stresses by simulation have good agreement with that by X-ray diffraction (XRD). The transverse residual stresses in the weld and HAZ are gradually decreased as the increases of heat input. The higher heat input can enhance the tensile strength and elongation of repaired joint. When the heat input was increased by 33%, the SCC sensitivity index was decreased by more than 60%. The macroscopic cracks are easily generated in HAZ for the smaller heat input, leading to the smaller tensile strength and elongation. The larger heat input is recommended in the repair welding in 304 stainless steel.
Dental Calculus as a Tool to Study the Evolution of the Mammalian Oral Microbiome

Abstract Dental calculus, the calcified form of the mammalian oral microbial plaque biofilm, is a rich source of oral microbiome, host, and dietary biomolecules and is well preserved in museum and archaeological specimens. Despite its wide presence in mammals, to date, dental calculus has primarily been used to study primate microbiome evolution. We establish dental calculus as a valuable tool for the study of nonhuman host microbiome evolution, by using shotgun metagenomics to characterize the taxonomic and functional composition of the oral microbiome in species as diverse as gorillas, bears, and reindeer. We detect oral pathogens in individuals with evidence of oral disease, assemble near-complete bacterial genomes from historical specimens, characterize antibiotic resistance genes, reconstruct components of the host diet, and recover host genetic profiles. Our work demonstrates that metagenomic analyses of dental calculus can be performed on a diverse range of mammalian species, which will allow the study of oral microbiome and pathogen evolution from a comparative perspective. As dental calculus is readily preserved through time, it can also facilitate the quantification of the impact of anthropogenic changes on wildlife and the environment.
Pt Nanoparticles with High Oxidase-Like Activity and Reusability for Detection of Ascorbic Acid

Noble metal nanoenzymes such as Pt, Au, Pd, etc. exhibit magnificent activity. However, due to the scarce reserves and expensive prices of precious metals, it is essential to investigate their enzyme-like activity and explore the possibility of their reuse. In this work, the oxidase-like activity and reusability of several Pt nanoparticles with different morphologies were detected. We compared the Pt nanoparticles (NPs) with a size of about 30 nm self-assembled by 5 nm Pt nanoparticles and Pt nanoparticles (Pt-0 HCl) with a diameter of about 5 nm, and found that their Michaelis−Menten constants (Km) were close and their initial performance similar, but the Pt NPs had better reusability. This was probably attributed to the stacked structure of Pt NPs, which was conducive to the substance transport and sufficient contact. At the same time, it was found that the size, dispersion, and organic substances adsorbed on the surface of Pt nanoparticles would have a significant impact on their reusability. A colorimetric detection method was designed using the oxidase-like activity of Pt NPs to detect ascorbic acid in triplicate. The limits of detection were 131 ± 15, 144 ± 14, and 152 ± 9 nM, with little difference. This research not only showed that the morphology of the catalyst could be changed and its catalytic performance could be controlled by a simple liquid phase synthesis method, but also that it had great significance for the reuse of Pt nanoenzymes in the field of bioanalysis.
Genetic association research in football: A systematic review

Abstract Genetic variation is responsible for a large amount of the inter-individual performance disparities seen in sport. As such, in the last ten years genetic association studies have become more common; with one of the most frequently researched sports being football. However, the progress and methodological rigour of genetic association research in football is yet to be evaluated. Therefore, the aim of this paper was to identify and evaluate all genetic association studies involving football players and outline where and how future research should be directed. Firstly, a systematic search was conducted in the Pubmed and SPORTDiscus databases, which identified 80 eligible studies. Progression analysis revealed that 103 distinct genes have been investigated across multiple disciplines; however, research has predominately focused on the association of the ACTN3 or ACE gene. Furthermore, 55% of the total studies have been published within the last four years; showcasing that genetic association research in football is increasing at a substantial rate. However, there are several methodological inconsistencies which hinder research implications, such as; inadequate description or omission of ethnicity and on-field positions. Furthermore, there is a limited amount of research on several key areas crucial to footballing performance, in particular; psychological related traits. Moving forward, improved research designs, larger sample sizes, and the utilisation of genome-wide and polygenic profiling approaches are recommended. Finally, we introduce the Football Gene Project, which aims to address several of these limitations and ultimately facilitate greater individualised athlete development within football.
Development of Algorithm for Clinical Management of Sickle Cell Bone Disease: Evidence for a Role of Vertebral Fractures in Patient Follow-up

Sickle-cell disease (SCD) is a worldwide distributed hemoglobinopathy, characterized by hemolytic anemia associated with vaso-occlusive events. These result in acute and chronic multiorgan damage. Bone is early involved, leading to long-term disability, chronic pain and fractures. Here, we carried out a retrospective study to evaluate sickle bone disease (SBD) in a cohort of adults with SCD. We assessed bone density, metabolism and turnover. We also evaluated the presence of fractures and the correlation between SCD severity and skeletal manifestations. A total of 71 patients with SCD were analyzed. The mean age of population was 39 ± 10 years, 56% of which were females. We found osteoporosis in a range between 7% and 18% with a high incidence of vertebral fractures. LDH and AST were predictive for the severity of vertebral fractures, while bone density was not. Noteworthy, we identified -1.4 Standard Deviations T-score as the cutoff for detecting the presence of fractures in patients with SCD. Collectively our data allowed us to develop an algorithm for the management of SBD, which may be useful in daily clinical practice to early intersect and treat SBD.
Engineering mesenchymal stem cells: a novel therapeutic approach in breast cancer

Abstract Breast cancer is one of the most prevalent and deadliest cancers among women in the world because of its aggressive behaviour and inadequate response to conventional therapies. Cellular and gene therapies based on mesenchymal stem cells (MSCs) represent promising treatment strategies for multiple diseases, such as cancers. MSCs are multipotent adult stem cells with important features for cell therapy, such as tissue homing to injured sites, their differentiation potential, their capacity of secreting plenty of trophic factors, and low immunogenicity. The quite easy isolation of these cells from various types of tissues are associated with no ethical concern when dealing with foetal or embryonic stem cells. The MSCs exhibit both pro and anti-oncogenic properties. However, genetic engineering of MSCs and nanoparticles is being employed as a means to solve some of these problems and improve the antitumor properties of these cells. The tumour-homing ability of MSCs and their exosomes to tumour niches have made them as a promising vector for targeted delivery of therapeutic agents to tumours site. The present study investigated MSCs specifications, pro- and anti-oncogenic properties of MSCs in breast cancer, and reviewed targeted breast cancer therapy via engineered MSCs, likely as potent cellular vehicles.
Evaluation of physicochemical, functional and sensory properties of fermented fura powder supplemented with soy

Pearl millet (Pennisetum glaucum [L.] R. Br.) with spices was processed into paste while soybean (Glycine max L Merill) was defatted and processed into soy meal. The millet paste was divided into three portions. The first portion was further processed into traditional fura (TF) (Control). The second portion of the paste was allowed to ferment at ambient temperature for 48 h, 30% of soy meal was added and processed into fura (FS). The third millet paste portion was not allowed to ferment but supplemented with 30% soy meal and processed into fura (NFS). The fura products were oven-dried and milled into powder which were subjected to standard methods of analyses for physicochemical and sensory properties while another sample was stored at room temperature; samples were withdrawn at intervals of 4 and 6 weeks for some functional properties evaluation. Results showed that FS and NFS had higher protein of 16.80% and 18.30% respectively than TF with 12.10%. Except for protein and fat, there was no significant difference (p >0.05) in the other values of the proximate composition among samples. There was no significant difference (p >0.05) in the chemical analysis among the fura samples. The bulk density increased with storage period; FS from 0.62 to 0.70g/cm3, TF 0.75 0.78g/3 while NFS ranged from 0.77 to 0.88g/cm3. Reconstitution index increased from 44 to 46% for TF, 46 to 53% for FS while NFS increased from 41 to 42%. Water absorption capacity (WAC) decreased from 55 to 46% for TF, 60 to 47% for FS while NFS decreased from 65 to 55%. Though FS had lowest rating for overall acceptability, there was no statistical difference among samples in taste, colour and texture. Fermented soy supplemented fura had a high nutrient value with good functional and sensory properties.
Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent.

BACKGROUND Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Anti-viral immune response is crucial to achieve pathogen clearance, however in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate pathogen elimination, immunity, and pathology is essential to better characterize disease progression and widen the spectrum of therapeutic options. METHODS We performed a flow cytometric characterization of immune cells subsets from 30 COVID-19 patients and correlated these data with clinical outcomes. RESULTS COVID-19 patients showed decreased numbers of circulating T, B and NK cells, and exhibited a skewing of CD8+ T cells towards a terminally differentiated/senescent phenotype. In agreement, T CD4+, T CD8+ but also NK cells displayed reduced anti-viral cytokine production capability. Moreover, a reduced cytotoxic potential was identified in COVID-19 patients, particularly in those that required intensive care. The latter group of patients showed also increased serum IL-6 levels, that correlated to the frequency of granzyme-expressing NK cells. Off-label treatment with tocilizumab restored the cytotoxic potential of NK cells. CONCLUSION In conclusion, the association between IL-6 serum levels and the impairment of cytotoxic activity suggests the possibility that targeting this cytokine may restore anti-viral mechanisms. FUNDING This study was supported by funds of Dept. of Experimental and Clinical Medicine of University of Florence (ex-60%) derived from Ministero dell'Istruzione, dell'Università e della Ricerca (Italy).
Intact Detection of Highly Occluded Immature Tomatoes on Plants Using Deep Learning Techniques

Automatic detection of intact tomatoes on plants is highly expected for low-cost and optimal management in tomato farming. Mature tomato detection has been wildly studied, while immature tomato detection, especially when occluded with leaves, is difficult to perform using traditional image analysis, which is more important for long-term yield prediction. Therefore, tomato detection that can generalize well in real tomato cultivation scenes and is robust to issues such as fruit occlusion and variable lighting conditions is highly desired. In this study, we build a tomato detection model to automatically detect intact green tomatoes regardless of occlusions or fruit growth stage using deep learning approaches. The tomato detection model used faster region-based convolutional neural network (R-CNN) with Resnet-101 and transfer learned from the Common Objects in Context (COCO) dataset. The detection on test dataset achieved high average precision of 87.83% (intersection over union ≥ 0.5) and showed a high accuracy of tomato counting (R2 = 0.87). In addition, all the detected boxes were merged into one image to compile the tomato location map and estimate their size along one row in the greenhouse. By tomato detection, counting, location and size estimation, this method shows great potential for ripeness and yield prediction.