Miracle-dz/UniFAR-FTUs huggingface dataset:
TGF-β1 secreted by M2 phenotype macrophages enhances the stemness and migration of glioma cells via the SMAD2/3 signalling pathway

The positive correlation between the number of M2 phenotype TAMs (M2-TAMs) and tumour development suggests a supportive role of M2-TAMs in glioma progression. In the present study, the molecular link between glioma cells and M2-TAMs was investigated and it was demonstrated that transforming growth factor-β1 (TGF-β1) secreted by M2-TAMs is key in facilitating the stemness and migration of glioma cells. Cluster of differentiation (CD)133 and CD44, markers for the M2 phenotype, were assessed by western blotting. A sphere formation assay and trans-well assay were applied to test the stemness and migration abilities of glioma cells following co-cultured with M2-TAMs. Stemness markers CD133 and CD44, epithelial-mesenchymal transition-associated markers and mothers against decapentaplegic homolog (SMAD)2/3 and sex determining region Y-box 4/2 (SOX4/2) levels were also evaluated by western blotting. A xenograft tumor mouse model was used to demonstrate the tumor forming ability of glioma cells. The results showed that the U251 glioma cells co-cultured with M2-TAMs exhibited high level of sphere formation, stemness and migration ability. Recombinant TGF-β1 protein treatment was able to achieve the same effects on U251 cells, whereas a TGF-β pathway inhibitor reversed the stemness and migration abilities of the glioma cells induced by M2-TAMs. It was also demonstrated that TGF-β1 secreted by M2-TAMs upregulated the phosphorylation of SMAD2/3 and the expression of SOX4/2 in glioma cells. In a mouse xenograft model, solid tumours formed by U251 cells co-cultured with M2-TAMs or pre-treated with TGF-β1 were larger in size and had a higher growth rate. Taken together, results of the present study demonstrated that M2-TAMs promoted the stemness and migration abilities of glioma cells by secreting TGF-β1, which activated the SMAD2/3 pathway and induced the expression of SOX4 and SOX2. These results highlight the mechanism by which M2-TAMs and glioma interact and demonstrate potential therapeutic strategies for glioma treatment.
Tree diversity regulates soil respiration through elevated tree growth in a microcosm experiment

Soil respiration is an essential component of carbon (C) cycling in terrestrial ecosystems. Despite increasing awareness of the significance of aboveground-belowground interactions, little is known about tree diversity effects on soil respiration and the underlying mechanisms. Here, we conducted a 105-days microcosm experiment in a climate chamber to test the effects of tree diversity (1, 2, and 4 species) on soil respiration. We expected tree diversity to affect soil respiration through changes in tree growth and surface litter decomposition (indicated by the litter mass loss). Our results show that soil respiration varied among the four focal tree species and increased with tree species richness. Path analysis revealed tree growth as the main mechanism driving soil respiration and explaining the tree diversity effect in this short-term experiment. Our results indicate that tree diversity and particular tree traits regulate C dynamics through balancing C storage (plant productivity) and C release (soil respiration).
Phytochemistry, Traditional Uses and Pharmacological Profile of Rose Hip: A Review.

BACKGROUND The fruit of genus Rosa, known as "rose hip", is frequently used in different traditional medicines. Rose hips have long been used to treat kidney stones, gastroenteric ailments, hypertension and respiratory problems such as bronchitis, cough and cold. AIM This review is focused on the ethnopharmacological uses of rose hip as well as phytochemical and pharmacological aspects. RESULTS Ethno-medical uses of rose hip have been recorded in many countries since a long time. Approximately, 129 chemical compounds have been isolated and identified from rose hip. This fruit contains some major active components such as flavonoids, tannins, anthocyanin, phenolic compounds, fatty oil, organic acids and inorganic compounds. Scientific studies have suggested a wide range of pharmacological activities for rose hip including antioxidant, anti-inflammatory, anti-obesity, anti-cancer, hepatoprotective, nephroprotective, cardioprotective, antiaging, anti H. pylori, neuroprotective and antinociceptive activities. In particular, the rose hip powder and extract have been reported to exert therapeutic effects on arthritis. CONCLUSION Some of the ethnomedical indications of rose hip, such as nephroprotective and gastroproetctive actions, have been confirmed by preclinical pharmacological studies. Additional investigations on the pharmacological effects of rose hip as well as evidence from randomized controlled trials are essential to assess the therapeutic value of this natural product.
Empowerment-driven Exploration using Mutual Information Estimation

Exploration is a difficult challenge in reinforcement learning and is of prime importance in sparse reward environments. However, many of the state of the art deep reinforcement learning algorithms, that rely on epsilon-greedy, fail on these environments. In such cases, empowerment can serve as an intrinsic reward signal to enable the agent to maximize the influence it has over the near future. We formulate empowerment as the channel capacity between states and actions and is calculated by estimating the mutual information between the actions and the following states. The mutual information is estimated using Mutual Information Neural Estimator and a forward dynamics model. We demonstrate that an empowerment driven agent is able to improve significantly the score of a baseline DQN agent on the game of Montezuma's Revenge.
Risk Factors of Rapid Cognitive Decline in Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.

BACKGROUND The conclusions about risk factors for rapid cognitive decline (RCD) in Alzheimer's disease (AD) and mild cognitive impairment (MCI) remain contradictory. OBJECTIVE To explore the factors predicting RCD in AD and MCI. METHODS We searched the PubMed, EMBASE, and the Cochrane Library from inception to May 27, 2017 for studies investigating factors associated with faster cognitive progression in AD and MCI. Effect sizes were meta-analyzed using fixed-effects and random-effects models. RESULTS Fifty-three studies with 14,330 patients (12,396 AD and 1,934 MCI) were included in the systematic review. The following factors were identified to increase the risk of RCD in AD: Apolipoprotein E4 (ApoE4) (SMD [95% CI]: 0.52 [0.06,0.98]), early age at onset (SMD [95% CI]: -0.42 [-0.71, -0.13]), high level of education (RR = 2.05, 95% CI = 1.26 to 3.33), early appearance of extrapyramidal signs (RR = 2.18; 95% CI = 1.30 to 3.67), and neuropsychiatric conditions including hallucination (RR = 2.01, 95% CI = 1.40 to 2.87), strolling (RR = 1.99, 95% CI = 1.38 to 2.86), agitation (RR = 1.66, 95% CI = 1.23 to 2.24), and psychosis (RR = 1.42, 95% CI = 1.07 to 1.89). Instead, advanced age (≥75 years) (RR = 0.96, 95% CI = 0.93 to 0.99), diabetes (RR = 0.57; 95% CI = 0.35 to 0.93), and multidrug therapy (RR = 0.61, 95% CI = 0.60 to 0.62) would lower the risk of RCD. Furthermore, systematic research also reviewed seven risk factors associated with RCD in MCI. CONCLUSION ApoE4, early onset, early appearance of extrapyramidal signs, high education level, and neuropsychiatric conditions might increase the risk of RCD while older age, diabetes, and multidrug therapy were the protective factors for AD.
Rethinking the Value of Network Pruning

Network pruning is widely used for reducing the heavy inference cost of deep models in low-resource settings. A typical pruning algorithm is a three-stage pipeline, i.e., training (a large model), pruning and fine-tuning. During pruning, according to a certain criterion, redundant weights are pruned and important weights are kept to best preserve the accuracy. In this work, we make several surprising observations which contradict common beliefs. For all state-of-the-art structured pruning algorithms we examined, fine-tuning a pruned model only gives comparable or worse performance than training that model with randomly initialized weights. For pruning algorithms which assume a predefined target network architecture, one can get rid of the full pipeline and directly train the target network from scratch. Our observations are consistent for multiple network architectures, datasets, and tasks, which imply that: 1) training a large, over-parameterized model is often not necessary to obtain an efficient final model, 2) learned "important" weights of the large model are typically not useful for the small pruned model, 3) the pruned architecture itself, rather than a set of inherited "important" weights, is more crucial to the efficiency in the final model, which suggests that in some cases pruning can be useful as an architecture search paradigm. Our results suggest the need for more careful baseline evaluations in future research on structured pruning methods. We also compare with the "Lottery Ticket Hypothesis" (Frankle & Carbin 2019), and find that with optimal learning rate, the "winning ticket" initialization as used in Frankle & Carbin (2019) does not bring improvement over random initialization.
Reconstituted HDL: Drug Delivery Platform for Overcoming Biological Barriers to Cancer Therapy

Drug delivery to malignant tumors is limited by several factors, including off-target toxicities and suboptimal benefits to cancer patient. Major research efforts have been directed toward developing novel technologies involving nanoparticles (NPs) to overcome these challenges. Major obstacles, however, including, opsonization, transport across cancer cell membranes, multidrug-resistant proteins, and endosomal sequestration of the therapeutic agent continue to limit the efficiency of cancer chemotherapy. Lipoprotein-based drug delivery technology, “nature’s drug delivery system,” while exhibits highly desirable characteristics, it still needs substantial investment from private/government stakeholders to promote its eventual advance to the bedside. Consequently, this review focuses specifically on the synthetic (reconstituted) high-density lipoprotein rHDL NPs, evaluating their potential to overcome specific biological barriers and the challenges of translation toward clinical utilization and commercialization. This highly robust drug transport system provides site-specific, tumor-selective delivery of anti-cancer agents while reducing harmful off-target effects. Utilizing rHDL NPs for anti-cancer therapeutics and tumor imaging revolutionizes the future strategy for the management of a broad range of cancers and other diseases.
Quorum sensing communication: Bradyrhizobium‐Azospirillum interaction via N‐acyl‐homoserine lactones in the promotion of soybean symbiosis

Quorum‐sensing (QS) mechanisms are important in intra‐ and inter‐specific communication among bacteria. We investigated QS mechanisms in Bradyrhizobium japonicum strain CPAC 15 and Azospirillum brasilense strains Ab‐V5 and Ab‐V6, used in commercial co‐inoculants for the soybean crop in Brazil. A transconjugant of CPAC 15‐QS with partial inactivation of N‐acyl‐homoserine lactones (AHLs) was obtained and several parameters were evaluated; in vitro, CPAC 15 and the transconjugant differed in growth, but not in biofilm formation, and no differences were observed in the symbiotic performance in vivo. The genome of CPAC 15 carries functional luxI and luxR genes and low amounts of three AHL molecules were detected: 3‐OH‐C12‐AHL, 3‐OH‐C14‐AHL, and 3‐oxo‐C14‐AHL. Multiple copies of luxR‐like genes, but not of luxI are present in the genomes of Ab‐V5 and Ab‐V6, and differences in gene expression were observed when the strains were co‐cultured with B. japonicum; we may infer that the luxR‐genes of A. brasilense may perceive the AHL molecules of B. japonicum. Soybean symbiotic performance was improved especially by co‐inoculation with Ab‐V6, which, contrarily to Ab‐V5, did not respond to the AHLs of CPAC 15. We concluded that A. brasilense Ab‐V5, but not Ab‐V6, responded to the QS signals of CPAC 15, and that the synergistic interaction may be credited, at least partially, to the QS interaction. In addition, we confirmed inter‐ and intra‐species QS communication between B. japonicum and A. brasilense and, for Azospirillum, at the strain level, impacting several steps of the symbiosis, from cell growth to plant nodulation and growth.
Understanding SOCS protein specificity

Abstract The development and activity of our immune system are largely controlled by the action of pleiotropic cytokines and growth factors, small secreted proteins, which bind to receptors on the surface of immune cells to initiate an appropriate physiological response. Cytokine signalling is predominantly executed by intracellular proteins known as the Janus kinases (JAKs) and the signal transducers and activators of transcriptions (STATs). Although the ‘nuts and bolts’ of cytokine-activated pathways have been well established, the nuanced way in which distinct cellular outcomes are achieved and the precise molecular details of the proteins that regulate these pathways are still being elucidated. This is highlighted by the intricate role of the suppressor of cytokine signalling (SOCS) proteins. The SOCS proteins act as negative feedback inhibitors, dampening specific cytokine signals to prevent excessive cellular responses and returning the cell to a homeostatic state. A great deal of study has demonstrated their ability to inhibit these pathways at the receptor complex, either through direct inhibition of JAK activity or by targeting the receptor complex for proteasomal degradation. Detailed analysis of individual SOCS proteins is slowly revealing the complex and highly controlled manner by which they can achieve specificity for distinct substrates. However, for many of the SOCS, a level of detail is still lacking, including confident identification of the full suite of tyrosine phosphorylated targets of their SH2 domain. This review will highlight the general mechanisms which govern SOCS specificity of action and discuss the similarities and differences between selected SOCS proteins, focusing on CIS, SOCS1 and SOCS3. Because of the functional and sequence similarities within the SOCS family, we will also discuss the evidence for functional redundancy.
The origins of happiness: the science of wellbeing

There seem to be few more popular topics to write about these days than happiness. We have noted before this rising tide in happiness studies (Guha & Carson, 2014). The authors of this latest treatise are from the Wellbeing Programme at the London School of Economics. Of the authors, I had only come across the work of Richard Layard before. Readers of this journal looking for a readable introduction to the field might find this tome heavy going and certainly Richard Layard’s other book Happiness: Lessons from a New Science (Layard, 2011) is a more gentle introduction to this area. This book sets out to chart happiness over the life span, and that is exactly what it does. The first part looks at what makes a happy adult? The second, what makes a successful child? The third part is entitled, “So what? ” Perhaps not the wisest choice of title? This is not an easy read. The authors do however warn us on Page 11, “. in this book we rely on naturalistic evidence, subjected to multiple regression analysis.most of the equations are broad brush linear equations. ” There are, however, helpful summaries in layman’s terms at the end of each chapter for the “faint hearted. ” Here, as in a lot of Lord Layard’s writing, we learn that “. the most common cause of deprivation is not poverty or unemployment, but mental illness. ” The authors of the book have policy makers as their target readership and suggest that rather than focussing exclusively on poverty, unemployment, education and physical health, the state needs to pay more attention, inter alia, to domestic violence, alcoholism, depression and anxiety. Herbert Van Rompuy, who was president of the European Council at the time, once gave copies of Leo Bormans’ World Book of Happiness to many of the world’s leading politicians (Bormans, 2012). I somehow doubt that he will be giving this book away.
Return to Work in Patients with Hematological Cancers 1 Year after Treatment: A Prospective Longitudinal Study

Background: Although hematological cancer survivors have a high risk of disability, data on work-related issues are scarce for this population. Methods: We investigated return to work (RTW) and work ability (Work Ability Index, WAI) in hematological cancer patients 6 months and 1 year after cancer treatment. We explored associations between baseline sociodemographic and medical characteristics and RTW as well as work ability at follow-up. Results: The participation rate was 42% (baseline n = 91, after 12 months n = 40 (44%)). 6 months after cancer treatment, 33% (95% confidence interval 21%-46%) of the remaining patients had returned to work. After 12 months, the RTW rate was 58% (42%-73%). Mean WAI sum score ± SD significantly increased from 18.5 ± 7.3 at baseline to 28.3 ± 8.3 after 12 months (p = 0.001). Patients with lymphoma (r = 0.31, p = 0.02) and patients who received radiation therapy (r = 0.29, p = 0.04) were significantly more likely to return to work. Work ability after 6 months was most strongly associated with higher education (r = 0.60, p < 0.01). Patients' subjective prognosis of gainful employment before cancer treatment predicted work ability after 6 (r = 0.62, p < 0.01) and 12 months (r = 0.51, p < 0.01). Conclusion: The chance of returning to work of hematological malignancy survivors is similar to that of other cancer patients.
Assembly-aware Design of Printable Electromechanical Devices

From smart toys and household appliances to personal robots, electromechanical devices play an increasingly important role in our daily lives. Rather than relying on gadgets that are mass-produced, our goal is to enable casual users to custom-design such devices based on their own needs and preferences. To this end, we present a computational design system that leverages the power of digital fabrication and the emergence of affordable electronics such as sensors and microcontrollers. The input to our system consists of a 3D representation of the desired device's shape, and a set of user-preferred off-the-shelf components. Based on this input, our method generates an optimized, 3D printable enclosure that can house the required components. To create these designs automatically, we formalize a new spatio-temporal model that captures the entire assembly process, including the placement of the components within the device, mounting structures and attachment strategies, the order in which components must be inserted, and collision-free assembly paths. Using this model as a technical core, we then leverage engineering design guidelines and efficient numerical techniques to optimize device designs. In a user study, which also highlights the challenges of designing such devices, we find our system to be effective in reducing the entry barriers faced by casual users in creating such devices. We further demonstrate the versatility of our approach by designing and fabricating three devices with diverse functionalities.
Intergenerational examination of pain and posttraumatic stress disorder symptoms among youth with chronic pain and their parents

Introduction: Posttraumatic stress disorder (PTSD) symptoms are prevalent among youth with chronic pain, and associated with poorer pain outcomes and health-related quality of life (HRQoL). Conceptual models suggest that parent factors, including parents' own chronic pain, may be linked to higher co-occurring pain and PTSD symptoms and lower HRQoL in children. However, this has not been empirically examined. Objectives: The aim of this study was to examine the relationship between parental chronic pain and (1) parent PTSD symptoms, (2) child PTSD symptoms, (3) child pain outcomes, and (4) child HRQoL in a sample of treatment-seeking youth with chronic pain and their parents. Methods: Youth (n = 173) aged 8 to 18 years and parents (n = 204) recruited from a tertiary-level pediatric chronic pain program completed psychometrically-sound measures of pain and PTSD symptoms. Youth also completed measures of pain interference and HRQoL. Results: Half of the parents in this sample reported chronic pain. A series of analyses of covariances revealed that parents with vs without chronic pain reported significantly higher PTSD symptoms, and children of parents with vs without chronic pain reported significantly higher PTSD symptoms and pain interference and lower HRQoL. Conclusion: Findings from this study suggest that having a parent with chronic pain may confer additional risk for children with chronic pain experiencing higher PTSD symptoms, poorer pain outcomes, and lower HRQoL than having a parent without chronic pain. This could be due to genetics or social learning. Future longitudinal research is needed to understand how parental pain influences co-occurring pain and PTSD symptoms, and HRQoL, in children.
Validation of Billewicz Scoring System for Detection of Overt Hypothyroidism During Pregnancy

Background Currently, various clinical and laboratory diagnostic methods are used to detect overt hypothyroidism during pregnancy. The Billewicz scoring index, as a clinical scale for detection of hypothyroidism, has been applied in general populations; however, its application during pregnancy remains a controversial subject of ongoing research. Objectives The purpose of this study was to evaluate the diagnostic value of Billewicz scoring index for overt hypothyroidism in a general population of Iranian pregnant women. Methods This study was conducted on 1843 pregnant women. A comprehensive questionnaire, including Billewicz scoring items, was completed, and relevant clinical examinations were performed. The participants underwent serum measurements of thyroxine (T4), thyroid hormone uptake, thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb). Using the receiver operating characteristic (ROC) curve analysis, the optimal sensitivity and specificity were determined as values with maximum yields on the Youden and Rsquo’s Index (sensitivity + specificity-1). Results The prevalence of overt hypothyroidism and subclinical hypothyroidism was 3.3% and 28.6%, respectively. Overall, 3.6%, 18.9%, and 50% of euthyroid, subclinical hypothyroid, and overt hypothyroid women were TPOAb-positive, respectively. The mean Billewicz scores of euthyroid, overt hypothyroid, and subclinical hypothyroid women were -41.16 (11.16), -17.11 (13.63), and -40.1 (11.2), respectively. Based on the Billewicz scale, at least one sign of hypothyroidism was reported in 38.84% (n, 491) of euthyroid women. Scores ≤ -26.5 (sensitivity, 100%; specificity, 90.82%) were considered as the optimal scores for predicting overt hypothyroidism (Ldquo, Norisk, and Rsquo). Conclusions The Billewicz clinical scoring system, as a reliable and inexpensive clinical tool, used along with laboratory measurements, can help screen overt hypothyroidism during pregnancy, primarily in low-resource settings.