Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimal control of acute myeloid leukaemia

Acute myeloid leukaemia (AML) is a blood cancer affecting the haematopoietic stem cells of the myeloid cell line. AML is routinely treated with chemotherapy, and so it is of great interest to develop optimal chemotherapy treatment strategies. In this work, we incorporate an immune response into a stem cell model of AML, since we find that previous models lacking an immune response are inappropriate for deriving optimal control strategies. Using optimal control theory, we produce continuous controls and bang-bang controls, corresponding to a range of objectives and parameter choices. Through example calculations, we provide a practical approach to applying optimal control using Pontryagin’s maximum principle. In particular, we describe and explore factors that have a profound influence on numerical convergence. We find that the convergence behaviour is sensitive to the method of control updating, the nature of the control, and to the relative weighting of terms in the objective function. All codes we use to implement optimal control are made available.
Transmit Power Minimization for a Multi-Hop SWIPT Decode-and-Forward Sensor Network

A study of a multi-hop decode-and-forward (DF) simultaneous wireless information and power transfer (SWIPT) sensor network system is presented in this work. In the studied system model, a source communicates with a destination through the aid of multi-hop relays which harvest energy from their received signals. We apply power splitting (PS) based SWIPT relaying protocols for the relays harvesting energy. Focused on DF relaying protocol, we aim to minimize the transmit power at the source under a set end-to-end throughput constraint by optimizing PS ratios at the relays. Based on convex optimization techniques, the globally optimal PS ratio solution is obtained as a closed-form solution. Numerical results demonstrate the efficacy of the proposed optimal design over the conventional fixed PS ratio scheme.
Subunit cell–level measurement of polarization in an individual polar vortex

We report accurates and informative measurement with subunit cell resolution for local polarization distribution in ferroelectrics. Recently, several captivating topological structures of electric dipole moments (e.g., vortex, flux closure) have been reported in ferroelectrics with reduced size/dimensions. However, accurate polarization distribution of these topological ferroelectric structures has never been experimentally obtained. We precisely measure the polarization distribution of an individual ferroelectric vortex in PbTiO3/SrTiO3 superlattices at the subunit cell level by using the atomically resolved integrated differential phase contrast imaging in an aberration-corrected scanning transmission electron microscope. We find, in vortices, that out-of-plane polarization is larger than in-plane polarization, and that downward polarization is larger than upward polarization. The polarization magnitude is closely related to tetragonality. Moreover, the contribution of the Pb─O bond to total polarization is highly inhomogeneous in vortices. Our precise measurement at the subunit cell scale provides a sound foundation for mechanistic understanding of the structure and properties of a ferroelectric vortex and lattice-charge coupling phenomena in these topological ferroelectric structures.
Risk of Cancers in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Results from the Korea National Health Insurance Claims Database 2010–2018

The association between antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and cancer remains poorly understood. In this study, we searched the Korea National Health Insurance Claims Database to obtain data for 2097 AAV patients, and evaluated the risk of cancers in AAV. The standardized incidence ratios (SIRs) of overall and site-specific cancers were estimated in patients with AAV compared to the general population. The overall risk of cancer was significantly higher in patients with AAV (SIR 1.90); this remained true in both males (SIR 1.74) and females (SIR 2.06). For site-specific cancers, the risks of lung (SIR 2.23) and hematological (SIR 11.39) cancers were higher in AAV patients. For males, the risks of gallbladder and hematological cancers were increased, while the risks of bladder and hematological cancers were increased in females. Among AAV subtypes, patients with granulomatosis with polyangiitis had the highest risk of cancers, and cyclophosphamide, azathioprine/mizoribine, and methotrexate ever-users had increased risk of overall cancer. The risks of overall and hematological cancers were elevated in AAV patients younger than 60 years old. Patients with AAV have increased risks of overall, lung, and hematological cancers. Distinct patterns of cancer incidence are present according to age, sex, AAV subtypes, and immunosuppressant usage.
Would a robot trust you? Developmental robotics model of trust and theory of mind

Trust is a critical issue in human–robot interactions: as robotic systems gain complexity, it becomes crucial for them to be able to blend into our society by maximizing their acceptability and reliability. Various studies have examined how trust is attributed by people to robots, but fewer have investigated the opposite scenario, where a robot is the trustor and a human is the trustee. The ability for an agent to evaluate the trustworthiness of its sources of information is particularly useful in joint task situations where people and robots must collaborate to reach shared goals. We propose an artificial cognitive architecture based on the developmental robotics paradigm that can estimate the trustworthiness of its human interactors for the purpose of decision making. This is accomplished using Theory of Mind (ToM), the psychological ability to assign to others beliefs and intentions that can differ from one’s owns. Our work is focused on a humanoid robot cognitive architecture that integrates a probabilistic ToM and trust model supported by an episodic memory system. We tested our architecture on an established developmental psychological experiment, achieving the same results obtained by children, thus demonstrating a new method to enhance the quality of human and robot collaborations. This article is part of the theme issue ‘From social brains to social robots: applying neurocognitive insights to human–robot interaction’.
Genetic diversity and maternal origin of Northeast African and South American donkey populations.

To investigate the mtDNA variation and origin of maternal lineages in South American donkeys and to reassess the domestication of donkeys in northeast Africa, we analyzed sequences (489 bp of the D-loop) from 323 domestic donkeys sampled from Peru, Brazil, Ethiopia and Egypt. Altogether, the 323 sequences displayed 53 different haplotypes (45 in Ethiopia, 14 in Egypt, eight in Peru and six in Brazil). Among the four populations, Egyptian donkeys possessed the highest haplotype diversity (0.910 ± 0.032), followed by Brazilian donkeys (0.879 ± 0.060). The Clade I haplotypes dominated in Peruvian donkeys (65%), whereas Clade II haplotypes dominated in Brazilian donkeys (67%). Estimates of FST values showed a high genetic differentiation between Peruvian and Brazilian donkey populations (FST = 0.4066), which could be explained by the complex introduction history of South American donkeys. Phylogeographic analysis indicates that northeast Africa could be the most probable domestication center for Clade I donkeys. Analysis of molecular variance confirmed a weak genetic structure in domestic donkey populations among four continents (Europe, Asia, Africa and South America).
TUBB1 dysfunction in inherited thrombocytopenia causes genome instability

Inherited thrombocytopenia is a genetically heterogeneous disease characterized by varying degrees of thrombocytopenia and risk of haematological malignancy, and the genetic cause of many cases remains unknown. We performed whole‐exome sequencing of a family with thrombocytopenia and myeloid malignancy and identified a novel TUBB1 variant, T149P. Screening of other thrombocytopenia pedigrees identified another TUBB1 variant, R251H. TUBB1 encodes the tubulin β‐1 chain, a major component of microtubules abundant in megakaryocytes. Variant TUBB1 disrupted the normal assembly of microtubules and impaired proplatelet formation in vitro. In addition, DNA damage response was severely attenuated by loss of TUBB1. We found that the nuclear accumulation of p53 (also termed TP53) and the expression of pro‐apoptotic genes triggered by genotoxic stress were blocked in TUBB1‐deficient cells and, accordingly, apoptosis after DNA damage was diminished by knockdown of TUBB1. Thus, we have demonstrated that microtubule dysfunction confers resistance to apoptosis, even in DNA damage‐accumulated cells, which explains genome instability in the affected individuals. These studies will lead us to a better understanding of how microtubule dysfunction can contribute to the accumulation of DNA damage, genetic instability and leukaemogenesis.
Identification of DHODH as a therapeutic target in small cell lung cancer

Small cell lung cancer tumors are sensitive to DHODH inhibition, highlighting a potential treatment strategy for this disease. A big step against small cell cancer Small cell lung cancer is a particularly aggressive tumor subtype, for which no specific targeted treatments are available. Li et al. used a CRISPR screening approach to identify a metabolic vulnerability and determine that small cell lung cancer cells are particularly reliant on the pyrimidine biosynthesis pathway and therefore sensitive to its disruption. The authors then demonstrated that brequinar, a pharmacological inhibitor of a key step in this pathway, is effective against small cell lung cancer in vitro and in multiple mouse models, including patient-derived xenografts. Small cell lung cancer (SCLC) is an aggressive lung cancer subtype with extremely poor prognosis. No targetable genetic driver events have been identified, and the treatment landscape for this disease has remained nearly unchanged for over 30 years. Here, we have taken a CRISPR-based screening approach to identify genetic vulnerabilities in SCLC that may serve as potential therapeutic targets. We used a single-guide RNA (sgRNA) library targeting ~5000 genes deemed to encode “druggable” proteins to perform loss-of-function genetic screens in a panel of cell lines derived from autochthonous genetically engineered mouse models (GEMMs) of SCLC, lung adenocarcinoma (LUAD), and pancreatic ductal adenocarcinoma (PDAC). Cross-cancer analyses allowed us to identify SCLC-selective vulnerabilities. In particular, we observed enhanced sensitivity of SCLC cells toward disruption of the pyrimidine biosynthesis pathway. Pharmacological inhibition of dihydroorotate dehydrogenase (DHODH), a key enzyme in this pathway, reduced the viability of SCLC cells in vitro and strongly suppressed SCLC tumor growth in human patient-derived xenograft (PDX) models and in an autochthonous mouse model. These results indicate that DHODH inhibition may be an approach to treat SCLC.
Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma

Objective Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC. Design Transcriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS). Results A total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset. DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025). Conclusion The DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.
The impact of modified exercise and relaxation therapy on chronic lower back pain in office workers: a randomized clinical trial

This study aimed to evaluate the effectiveness of a modified package of exercise therapy combined with relaxation on pain intensity, range of motion (ROM), anxiety, and quality of life (QoL) in office workers with chronic lower back pain. In this clinical trial, 72 office workers aged 20 to 50 years with chronic low back pain were randomized to one of four groups including; group 1, exercise therapy; group 2, psychotherapy (relaxation therapy); group 3, modified protocol (exercise therapy followed by relaxation therapy); group 4, control group (no intervention). Participants exercised 3 times weekly for 6 weeks for 40–45 min of exercise/relaxation. Pain intensity, ROM, anxiety, and QoL were evaluated at baseline, 6 weeks, and 12 weeks after the end of the intervention. Results showed significant decreases in pain intensity and anxiety in the three experimental groups compared to the control group. The three intervention groups indicated a significant decrease in pain intensity and anxiety after 6 and 12 weeks. ROM significantly improved in the exercise therapy and the modified protocol over time (after 6 and 12 weeks). A significant difference in QoL was found between the groups, with the greatest improvement found in the psychotherapy and modified protocol groups. This therapeutic package (including exercise movements and psychological interventions) was found to have a superior effect on pain intensity, ROM, anxiety, and QoL after 6 and 12 weeks compared to other interventions (only exercise and psychotherapy).
From social brains to social robots: applying neurocognitive insights to human–robot interaction

Amidst the fourth industrial revolution, social robots are resolutely moving from fiction to reality. With sophisticated artificial agents becoming ever more ubiquitous in daily life, researchers across different fields are grappling with the questions concerning how humans perceive and interact with these agents and the extent to which the human brain incorporates intelligent machines into our social milieu. This theme issue surveys and discusses the latest findings, current challenges and future directions in neuroscience- and psychology-inspired human–robot interaction (HRI). Critical questions are explored from a transdisciplinary perspective centred around four core topics in HRI: technical solutions for HRI, development and learning for HRI, robots as a tool to study social cognition, and moral and ethical implications of HRI. Integrating findings from diverse but complementary research fields, including social and cognitive neurosciences, psychology, artificial intelligence and robotics, the contributions showcase ways in which research from disciplines spanning biological sciences, social sciences and technology deepen our understanding of the potential and limits of robotic agents in human social life. This article is part of the theme issue ‘From social brains to social robots: applying neurocognitive insights to human–robot interaction’.
Comparison of Clinical Manifestation, Diagnosis, and Outcomes of Invasive Pulmonary Aspergillosis and Pulmonary Mucormycosis

Objects: Invasive pulmonary mold infection usually has devastating outcomes. Timely differentiation between invasive pulmonary aspergillosis (IPA) from pulmonary mucormycosis (PM) is critical for treatment decision-making. However, information on IPA and PM differentiation is limited. Methods: We conducted a retrospective, multicenter, observational study, with proven and probable IPA and PM patients from January 2004 to December 2017. Demographics, clinical manifestations, image reports, histopathological findings, and outcomes were analyzed. Results: A total of 46 IPA (33 proven and 13 probable) and 19 PM (18 proven and one probable) cases were analyzed. The majority of tissues (81% in IPA and 61% in PM) were obtained using bronchoscopy. Prior influenza infection was a predisposing factor for IPA, and abscess formation in CT scan was associated with PM (p = 0.0491, p = 0.0454, respectively). The positive culture rate for PM was lower than that for IPA (37% vs. 67%, p = 0.0294). The galactomannan (GM) level from serum and bronchoalveolar lavage (BAL) fluid was significantly higher in IPA than in PM (3.3 ± 0.5 vs. 0.8 ± 0.6, p = 0.0361; 4.0 ± 0.6 vs. 0.59 ± 0.1, p = 0.0473, respectively). The overall mortality rate was 65%, which was similar among IPA and PM groups. Systemic steroid exposure and high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores on admission were independently correlated to mortality in IPA (p = 0.027, p = 0.026, respectively). However, there was no predictor for mortality found in PM patients. Conclusions: Influenza infection, abscess formation in CT scan, and GM level may help physicians to differentiate IPA and PM. Bronchoscopy-guided biopsy and lavage specimen provide timely and definite diagnosis. The prognosis of IPA is associated with systemic steroid exposure and higher APACHE II scores on admission.
microRNA‐203 promotes proliferation, differentiation, and migration of osteoblasts by upregulation of Msh homeobox 2

Despite the improvements in fracture healing, about 10% of patients undergo abnormal healing. As a tumor suppressor, upregulation of microRNA (miR)‐203 has been observed in osteogenic differentiation. Herein, we aimed to explore the functional role of miR‐203 in osteoblasts as well as the underlying mechanisms. The expression of miR‐203 in MC3T3‐E1 cells that underwent osteogenic differentiation was determined by quantitative reverse transcription PCR (qRT‐PCR). The effects of aberrantly expressed miR‐203 on cell viability, migration, and expressions of proteins associated with proliferation, migration, and osteogenic differentiation were measured by using a Cell Counting Kit‐8 assay, Transwell cell migration assay, and western blot/qRT‐PCR, respectively. The possible downstream factor of miR‐203 was subsequently studied. Finally, involvements of the mitogen‐activated protein kinase (MAPK)/activator of transcription (STAT) pathways were assessed by western blot. We found that the miR‐203 level was increased in osteogenic differentiation of MC3T3‐E1 cells with increasing duration time (28th day, p < 0.001). After cell transfection, we interestingly found that miR‐203 overexpression could increase cell viability (p < 0.05), promote proliferation, migration (p < 0.05), and osteogenic differentiation, and upregulate Msh homeobox 2 (Msx2) expression. Furthermore, Msx2 knockdown was proved to abrogate the effects of miR‐203 overexpression on MC3T3‐E1 cells. Finally, phosphorylated levels of key kinases in the MAPK/STAT pathways were increased by miR‐203 overexpression via upregulating Msx2 expression. In conclusion, miR‐203 overexpression promoted proliferation, migration, and osteogenic differentiation of MC3T3‐E1 cells through upregulating Msx2 along with activation of the MAPK/STAT pathways.
Rat Left Ventricular Cardiomyocytes Characterization in the Process of Postinfarction Myocardial Remodeling

Ischemic lesions of the heart, including myocardial infarction, are the most common pathologies of human cardiovascular system. Despite all the research and achievements of medicine in this field, the mortality from this disease remains heavy. Therefore, studying of processes occurring in the myocardium in the early and late postinfarction periods remains important. Rat left ventricular cardiomyocyte (CMC) ploidy, hypertrophy, hyperplasia, and ultrastructure were investigated in 2, 6, and 26 weeks after experimental myocardial infarction, caused by permanent ligation of left coronary artery. Cytofluorimetric study of CMC ploidy revealed no difference between normal, sham‐operated, and infarcted animals for all the tested stages. However, interference microscopy indicated significant changes in cells size. CMC dry mass of infarcted rats in 2 weeks after surgery was 1.5 times lower than in control and sham operated groups. Electron microscopy analysis of CMC revealed disruption of sarcomere structure. However, in 6 weeks after surgery CMC dry mass was 1.6 times higher than in control. In 26 weeks after myocardial infarction CMC dry mass exceeded control only in peri‐infarction zone. Cell counting showed that the number of left ventricular CMC, reduced as a result of myocardial infarction, was not restored during myocardial remodeling. © 2019 International Society for Advancement of Cytometry
Degradable Calcium Phosphate-Coated Upconversion Nanoparticles for Highly Efficient Chemo-Photodynamic Therapy.

The development of a stimulus-responsive nanosystem provides an effective method for improving the accuracy and efficiency of chemotherapy. Meanwhile, traditional photodynamic therapy (PDT) has been substantially restricted by the low dosage of photosensitizer and limited penetration depth of the ultraviolet (UV) or visible light used for excitation. Here, we designed a smart multifunctional nanoplatform by coating a core-shell composite (mesoporous silica encapsulated up-conversion nanoparticles (UCNPs) and chlorin (Ce6) with degradable calcium phosphate, followed by the loading of doxorubicin (DOX). In our structure, the as-synthesized nanoplatform exhibits high responsiveness to a low pH value and degrade rapidly in the weakly acidic tumor microenvironment, allowing the quick release of loaded DOX in tumor sites. Interestingly, the loaded DOX, whose release depends on the pH value and positively correlates with the calcium ion concentration, enables drug release to be monitored in real time. Combined with photosensitizer Ce6-induced PDT triggered by 808 nm NIR light, synergistic chemo-photodynamic therapy is achieved, thus leading to a highly efficient anticancer treatment in vitro and in vivo. Importantly, the inherent properties of rare earth ions (Gd3+, Yb3+, and Nd3+) make the nanoplatform possess UCL, MRI, and CT tri-mode imaging capabilities, thus achieving a multiple imaging modality-guided synergistic therapy.