Miracle-dz/UniFAR-FTUs huggingface dataset:
CXCL12 induces migration of oligodendrocyte precursor cells through the CXCR4-activated MEK/ERK and PI3K/AKT pathways

Demyelination is a nervous system disease in which the myelin sheaths of neurons are damaged due to inflammatory reactions, inherited abnormalities or trauma. This damage impairs the conduction of signals in the affected nerves, which in turn causes deficiencies in sensation, movement and cognition. Oligodendrocyte precursor cells (OPCs) are able to induce remyelination. However, the remyelination is suboptimal due to the limited migration of OPCs. In the present study, neonatal OPCs were isolated from rats for the investigation of the role of C-X-C motif chemokine ligand 12 (CXCL12), an important chemokine, in mediating the migration ability of OPCs. The present results demonstrated that CXCL12 stimulation markedly promoted the migration of OPCs and activated the dual specificity mitogen-activated protein kinase kinase 1 (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/RAC-α serine/threonine-protein kinase (AKT) pathways. Knockdown of C-X-C motif chemokine receptor 4 (CXCR4; a receptor of CXCL12) reversed the CXCL12-induced migration of OPCs and blocked the MEK/ERK and PI3K/AKT pathways. In addition, specific inhibitors of the MEK/ERK and PI3K/AKT pathways significantly reduced the migration of OPCs. Based on these findings, it was concluded that CXCL12 may induce the migration of OPCs through the CXCR4-activated MEK/ERK and PI3K/AKT pathways. The results of the present study support the manipulation of CXCL12-mediated OPC migration to improve remyelination.
Radiologic and Pathological Investigation of Pseudarthrosis in Ankylosing Spondylitis: Distinguishing Between Inflammatory and Traumatic Etiology

Objective. To investigate the pathogenesis of pseudarthrosis in ankylosing spondylitis (AS) based on the pathological analysis of specimens harvested during surgery. Methods. Radiographic and clinical data for 17 consecutive AS patients with pseudarthrosis were retrospectively analyzed. Meanwhile, the pathological analysis of specimens obtained during surgery was also performed. Results. In total, 18 extensive Andersson lesions were included. Pseudarthrosis located at the apical region were noted in 12 patients. Complete ossified anterior longitudinal ligaments above or below pseudarthrosis and fracture through posterior elements or facet joints were observed in 7 and 6 lesions, respectively. The most definitive pathological characteristic in all cases was proliferating hypovascular edematous fibrous tissue involving disc, bone-disc border, and vertebral body. Fibrinoid necrosis, necrotic bone fragments, hemosiderin deposits, and active subchondral osteogenesis were found, indicating trauma process. Mild perivascular collections of inflammatory cells were detected in only 2 cases. Conclusion. AS-related pseudarthrosis is more likely to originate from mechanical trauma than inflammation. The above-mentioned radiological and histological findings showed that multiple mechanisms lead to the formation of pseudarthrosis. These mechanisms include excessive stress, insufficiency fracture, and an acute fracture involving a 3-column structure.
Partially ablative radiotherapy (PAR) for large mass tumors using simultaneous integrated boost: A dose‐escalation feasibility study

Abstract Purpose This study aimed to assess the feasibility to plan and deliver highly heterogeneous doses to symptomatic large tumors using volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) during a short course palliative accelerated radiotherapy. Methods A patient with a large symptomatic chordoma infiltrating the right gluteal region was selected. A modified SIB treatment was implemented to irradiate the central volume of the tumor (boost target volume, BTV) up to 10 Gy/fraction in a dose escalation trial while maintaining the remaining tumor volume (planning target volume, PTV) and the surrounding healthy tissues within 5 Gy/fraction in twice daily fractions for two consecutive days. Four SIB plans were generated in the dual‐arc modality; a basal dose of 20 Gy was prescribed to the PTV, while the BTV was boosted up to 40 Gy. For comparison purposes, plans obtained with a sequential boost (SEQ plans) were also generated. All plans were optimized to deliver at least 95% of the prescription dose to the targets. Dose contrast index (DCI), conformity index (CI), integral dose (ID), and the irradiated body volumes at 5, 10, and 20 Gy were evaluated. Results At equal targets coverage, SIB plans provided major improvement in DCI, CI, and ID with respect to SEQ plans. When BTV dose escalated up to 200% of PTV prescription, DCI resulted in 66% for SIB plans and 37% for SEQ plans; the ID increase was only 11% for SIB plans (vs 27% for SEQ plans) and the increase in healthy tissues receiving more than 5, 10, and 20 Gy was less than 2%. Pretreatment dose verification reported a γ‐value passing rate greater than 95% with 3%(global)‐2 mm. Conclusion A modified SIB technique is dosimetrically feasible for large tumors, where doses higher than the tolerance dose of healthy tissues are necessary to increase the therapeutic gain.
Motivation for sport participation and eating disorder risk among female collegiate athletes

ABSTRACT In light of conflicting research regarding eating disorder risk and sports participation, the current study examined the relationship between specific aspects of sports participation (i.e., level of competition, leanness requirements, and physical/cardiovascular intensity level), an individual’s motivation for sports participation, and eating disorder symptomatology/risk. Participants included 319 female collegiate athletes (M age = 19.88; SD = 1.62) representing a variety of sports and competition levels. Multilevel modeling found that level of competition, receiving a scholarship, age, and years of collegiate sport played did not predict eating disorder risk. In the final model, there was a significant interaction between intrinsic motivation and sport intensity. For high intensity sports, higher levels of intrinsic motivation were associated with lower eating disorder risk. For low intensity sports, the level of intrinsic motivation did not impact eating disorder risk. For all sport intensities, extrinsic motivation was associated with a higher eating disorder risk. Results suggest that it is not the specific sport but athletes’ motivation for those sports with high physical/cardiovascular intensity and leanness requirements that is associated with untoward consequences. The results clarify conflicting results previously reported in the literature that have primarily employed univariate analyses and have implications for athletic development programs.
Dual targeting of HSP70 does not induce the heat shock response and synergistically reduces cell viability in muscle invasive bladder cancer

Muscle invasive bladder cancer (MIBC) is a common malignancy and major cause of morbidity worldwide. Over the last decade mortality rates for MIBC have not decreased as compared to other cancers indicating a need for novel strategies. The molecular chaperones HSP70 and HSP90 fold and maintain the 3-dimensional structures of numerous client proteins that signal for cancer cell growth and survival. Inhibition of HSP70 or HSP90 results in client protein degradation and associated oncogenic signaling. Here we targeted HSP70 and HSP90 with small molecule inhibitors that trap or block each chaperone in a low client-affinity “open” conformation. HSP70 inhibitors, VER155008 (VER) and MAL3-101 (MAL), along with HSP90 inhibitor, STA-9090 (STA), were tested alone and in combination for their ability to reduce cell viability and alter protein levels in 4 MIBC cell lines. When combined, VER+MAL synergistically reduced cell viability in each MIBC cell line while not inducing expression of heat shock proteins (HSPs). STA+MAL also synergistically reduced cell viability in each cell line but induced expression of cytoprotective HSPs indicating the merits of targeting HSP70 with VER+MAL. Additionally, we observed that STA induced the expression of the stress-related transcription factor HSF2 while reducing levels of the co-chaperone TTI1.
Involvement of GLUT1-mediated glucose transport and metabolism in gefitinib resistance of non-small-cell lung cancer cells

Use of epidermal growth factor receptor (EGFR) inhibitors represented by gefitinib and erlotinib has become the standard of treatment for non-small-cell lung cancers (NSCLCs) with activating EGFR mutations. However, the majority of NSCLCs, which overexpress EGFR without such mutations, are resistant to EGFR inhibitors, and the mechanism(s) behind such primary resistance of NSCLCs without activating EGFR mutations to EGFR inhibitors still remains poorly understood. Here in this study, we show that glucose metabolism mediated by GLUT1, a facilitative glucose transporter, is involved in gefitinib resistance of NSCLC cells. We found that GLUT1 expression and glucose uptake were increased in resistant NSCLC cells after gefitinib treatment and that genetic as well as pharmacological inhibition of GLUT1 sensitized not only NSCLC cells with primary resistance but also those with acquired resistance to gefitinib. In vivo, the combination of systemic gefitinib and a GLUT1 inhibitor, both of which failed to inhibit tumor growth when administered alone, significantly inhibited the growth of xenograft tumors formed by the implantation of NSCLC cells with wild-type EGFR (wt-EGFR). Since our data indicated that GLUT1 was similarly involved in erlotinib resistance, our findings suggest that the activity of GLUT1-mediated glucose metabolism could be a critical determinant for the sensitivity of NSCLC cells to EGFR inhibitors and that concurrent GLUT1 inhibition may therefore be a mechanism-based approach to treating NSCLCs resistant to EGFR inhibitors, including those with wt-EGFR.
Network Recasting: A Universal Method for Network Architecture Transformation

This paper proposes network recasting as a general method for network architecture transformation. The primary goal of this method is to accelerate the inference process through the transformation, but there can be many other practical applications. The method is based on block-wise recasting; it recasts each source block in a pre-trained teacher network to a target block in a student network. For the recasting, a target block is trained such that its output activation approximates that of the source block. Such a block-by-block recasting in a sequential manner transforms the network architecture while preserving the accuracy. This method can be used to transform an arbitrary teacher network type to an arbitrary student network type. It can even generate a mixed-architecture network that consists of two or more types of block. The network recasting can generate a network with fewer parameters and/or activations, which reduce the inference time significantly. Naturally, it can be used for network compression by recasting a trained network into a smaller network of the same type. Our experiments show that it outperforms previous compression approaches in terms of actual speedup on a GPU.
Safety and Impact of Low-dose Methotrexate on Endothelial Function and Inflammation in Individuals With Treated Human Immunodeficiency Virus: AIDS Clinical Trials Group Study A5314.

BACKGROUND Chronic inflammation in treated HIV infection is associated with mortality and atherosclerotic cardiovascular disease (ASCVD). We evaluated the safety and potential efficacy of low-dose methotrexate (LDMTX) in treated HIV. METHODS This was a phase 2 randomized, double-blind, multicenter trial in adults ≥40 years old with treated HIV, with CD4+ T-cell count ≥400 cells/μL and with/at increased risk for ASCVD. Participants received LDMTX (5-15 mg/week) or placebo (plus folic acid) for 24 weeks and were followed for an additional 12 weeks. Primary endpoints were safety and brachial artery flow-mediated dilation (FMD). RESULTS The 176 participants (90% male) had a median (Q1, Q3) age of 54 (49, 59) years. LDMTX was associated with decreases in CD4+ T cells at week 24 and CD8+ T cells at weeks 8, 12, and 24. Eleven participants (12.8%) experienced safety events in the LDMTX group vs 5 (5.6%) in placebo (Δ = 7.2%, upper 1-sided 90% CI, 13.4%; Pnoninferiority = .037). Week 24 change in FMD was 0.47% with LDMTX and 0.09% with placebo (P = .55). No inflammatory markers changed differentially with LDMTX compared to placebo. CONCLUSIONS Adults with HIV and increased ASCVD risk treated with LDMTX had more safety events than with placebo, but the prespecified noninferiority margin of 15% was not exceeded. LDMTX had no significant effect on endothelial function or inflammatory biomarkers but was associated with a significant decrease in CD8+ T cells. The balance of risks and potential benefits of LDMTX in this population will require additional investigation. CLINICAL TRIALS REGISTRATION NCT01949116.
Obesity causes PGC‐1α deficiency in the pancreas leading to marked IL‐6 upregulation via NF‐κB in acute pancreatitis

Obesity is associated with local and systemic complications in acute pancreatitis. PPARγ coactivator 1α (PGC‐1α) is a transcriptional coactivator and master regulator of mitochondrial biogenesis that exhibits dysregulation in obese subjects. Our aims were: (1) to study PGC‐1α levels in pancreas from lean or obese rats and mice with acute pancreatitis; and (2) to determine the role of PGC‐1α in the inflammatory response during acute pancreatitis elucidating the signaling pathways regulated by PGC‐1α. Lean and obese Zucker rats and lean and obese C57BL6 mice were used first; subsequently, wild‐type and PGC‐1α knockout (KO) mice with cerulein‐induced pancreatitis were used to assess the inflammatory response and expression of target genes. Ppargc1a mRNA and protein levels were markedly downregulated in pancreas of obese rats and mice versus lean animals. PGC‐1α protein levels increased in pancreas of lean mice with acute pancreatitis, but not in obese mice with pancreatitis. Interleukin‐6 (Il6) mRNA levels were dramatically upregulated in pancreas of PGC‐1α KO mice after cerulein‐induced pancreatitis in comparison with wild‐type mice with pancreatitis. Edema and the inflammatory infiltrate were more intense in pancreas from PGC‐1α KO mice than in wild‐type mice. The lack of PGC‐1α markedly enhanced nuclear translocation of phospho‐p65 and recruitment of p65 to Il6 promoter. PGC‐1α bound phospho‐p65 in pancreas during pancreatitis in wild‐type mice. Glutathione depletion in cerulein‐induced pancreatitis was more severe in KO mice than in wild‐type mice. PGC‐1α KO mice with pancreatitis, but not wild‐type mice, exhibited increased myeloperoxidase activity in the lungs, together with alveolar wall thickening and collapse, which were abrogated by blockade of the IL‐6 receptor glycoprotein 130 with LMT‐28. In conclusion, obese rodents exhibit PGC‐1α deficiency in the pancreas. PGC‐1α acts as selective repressor of nuclear factor‐κB (NF‐κB) towards IL‐6 in pancreas. PGC‐1α deficiency markedly enhanced NF‐κB‐mediated upregulation of Il6 in pancreas in pancreatitis, leading to a severe inflammatory response. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Image Superresolution Using Densely Connected Residual Networks

Recently, convolutional neural networks (CNN) have achieved impressive breakthroughs in single image superresolution. In particular, an efficient nonlinear mapping by increasing the depth and width of the network can be learned between the low-resolution input image and the high-resolution target image. However, this will lead to a substantial increase in network parameters, requiring the massive amount of training data to prevent overfitting. Besides, most CNN-based methods ignore the full use of different levels of features and, therefore, achieve relatively low performance. In this letter, we propose a deep convolutional network named densely connected residual networks (DRNet). Our proposed DRNet can reach very deep and wide while requiring fewer parameters. The significant performance improvement of our model is mainly due to the integration of dense skip connection and residual learning. In this way, DRNet mitigates the problems of overfitting, vanishing gradient, and training instability during training very deep and wide networks. Moreover, it can improve the propagation and reuse of features by creating direct connections from the previous layers to the subsequent layers. We evaluate the proposed method using images from four benchmark datasets and set a new state of the art.
Transaction Fraud Detection Based on Total Order Relation and Behavior Diversity

With the popularization of online shopping, transaction fraud is growing seriously. Therefore, the study on fraud detection is interesting and significant. An important way of detecting fraud is to extract the behavior profiles (BPs) of users based on their historical transaction records, and then to verify if an incoming transaction is a fraud or not in view of their BPs. Markov chain models are popular to represent BPs of users, which is effective for those users whose transaction behaviors are stable relatively. However, with the development and popularization of online shopping, it is more convenient for users to consume via the Internet, which diversifies the transaction behaviors of users. Therefore, Markov chain models are unsuitable for the representation of these behaviors. In this paper, we propose logical graph of BP (LGBP) which is a total order-based model to represent the logical relation of attributes of transaction records. Based on LGBP and users’ transaction records, we can compute a path-based transition probability from an attribute to another one. At the same time, we define an information entropy-based diversity coefficient in order to characterize the diversity of transaction behaviors of a user. In addition, we define a state transition probability matrix to capture temporal features of transactions of a user. Consequently, we can construct a BP for each user and then use it to verify if an incoming transaction is a fraud or not. Our experiments over a real data set illustrate that our method is better than three state-of-the-art ones.
Ultrastructure Study of the Stored Lipid Reserves in Gyrodactylus gasterostei (Monogenea) Using Confocal and Transmission Electron Microscopy

This study examines the distribution and depletion of stored lipids in Gyrodactylus gasterostei Gläser, 1974, migrating off its three-spine stickleback host Gasterosteus aculeatus L. , with the prospect that it might prove informative for interpreting the biology of other gyrodactylids species more generally. Nonfeeding life cycle stages, such as the dispersal stages of parasites, are dependent for survival upon finite energy reserves gathered during feeding phases. Thus, those individuals with more limited reserves will die sooner and consequently have less time available to find a new host once detached. At this stage, the principal energy reserves in gyrodactylids are stored as large lipid droplets. Confocal laser scanning microscopy has been used to investigate the distribution of lipid droplets in Gyrodactylus, which have migrated off their fish host, testing the hypothesis that these droplets function as a proxy for the nutritional state. This study demonstrated that the lipid droplets were particularly associated with the gut and that there is a significant variability in the volume of stored lipid carried out by each individual. Transmission electron microscopy showed that gyrodactylids carry lipid droplets at all stages of their life cycle, including at release from the birth pore. It is likely that transferring worms requires stored energy reserves to survive in the event of failure to establish contact with a new host. These reserves could allow the parasite to survive without a host for several days.
Psychopathology of Israeli Soldiers Presenting to a General Hospital Emergency Department: Lessons for the Attending Physician and Psychiatrist.

BACKGROUND There is scant research on the psychopathology of Israeli soldiers who present to a general hospital emergency department (ED). OBJECTIVES To assess the psychopathology among a cohort of Israeli soldiers who presented to a general hospital ED for mental health assessment. METHODS The demographic and clinical characteristics of 124 consecutive soldiers who presented to the ED for psychiatric assessment between January 2008 and September 2012 were reviewed. Twenty-seven soldiers from the cohort were contacted for follow-up by telephone on average 52 months later. RESULTS The reasons for presentation to the ED, usually during the early stages of military service, included self-harming behavior, suicidal ideation, somatoform complaints, and dissatisfaction with their military service. Psychiatric diagnoses included adjustment disorder and personality disorder. Self-harming behavior/suicidal ideation was significantly correlated with unspecified adjustment disorder (P = 0.02) and personality disorder (P = 0.001). At follow-up, there was a lack of substantial psychopathology: none of the subjects engaged in self-harming behavior/suicidal ideation and a consistent trend was observed toward clinical improvement. CONCLUSIONS Psychiatric intervention of soldiers who present to a general hospital ED because of emotional difficulties may provide the opportunity for crisis intervention and validation of the soldier's distress. To the best of our knowledge this is the first Israeli study of psychopathology among soldiers who presented to an ED.
Kicking foot swing planes and support leg kinematics in rugby place kicking: Differences between accurate and inaccurate kickers

Abstract Place kicking is a complex whole-body movement that contributes 45% of the points scored in international Rugby Union. This study compared the kicking foot swing plane characteristics of accurate and inaccurate kickers, underpinned by differences in their support leg and pelvis kinematics at support foot contact, to identify key technique characteristics. Motion capture data (240 Hz) were collected from 33 experienced kickers, and distinct groups of accurate (n = 18) and inaccurate (n = 8) kickers were identified based on their performance characteristics. All accurate kickers were capable of kicking successfully from at least 33.3 m, whereas all inaccurate kickers would have missed left from distances greater than 30.7 m. The accurate group exhibited a moderately shallower swing plane inclination (50.6 ± 4.8° vs. 54.3 ± 2.1°) and directed the plane moderately further to the right of the target (20.2 ± 5.4° vs. 16.7 ± 4.1°). At support foot contact, the accurate group placed their support foot moderately less far behind the ball (0.08 ± 0.08 m vs. 0.12 ± 0.04 m) and positioned their centre of mass moderately further to the support leg side (0.77 ± 0.07 m vs. 0.72 ± 0.01 m) due to a moderately greater stance leg lean (29.3 ± 4.1° vs. 26.8 ± 3.2°). The kicking foot swing plane is highly planar in rugby place kicking but its orientation differs between accurate and inaccurate kickers. These plane characteristics may be controlled by support foot placement and support leg and pelvis kinematics at support foot contact.