Miracle-dz/UniFAR-FTUs huggingface dataset:
Virotherapy combined with anti-PD-1 transiently reshapes the tumor immune environment and induces anti-tumor immunity in a preclinical PDAC model

Introduction Pancreatic ductal adenocarcinoma (PDAC) is largely refractory to cancer immunotherapy with PD-1 immune checkpoint blockade (ICB). Oncolytic virotherapy has been shown to synergize with ICB. In this work, we investigated the combination of anti-PD-1 and oncolytic measles vaccine in an immunocompetent transplantable PDAC mouse model. Methods We characterized tumor-infiltrating T cells by immunohistochemistry, flow cytometry and T cell receptor sequencing. Further, we performed gene expression profiling of tumor samples at baseline, after treatment, and when tumors progressed. Moreover, we analyzed systemic anti-tumor and anti-viral immunity. Results Combination treatment significantly prolonged survival compared to monotherapies. Tumor-infiltrating immune cells were increased after virotherapy. Gene expression profiling revealed a unique, but transient signature of immune activation after combination treatment. However, systemic anti-tumor immunity was induced by virotherapy and remained detectable even when tumors progressed. Anti-PD-1 treatment did not impact anti-viral immunity. Discussion Our results indicate that combined virotherapy and ICB induces anti-tumor immunity and reshapes the tumor immune environment. However, further refinement of this approach may be required to develop its full potential and achieve durable efficacy.
Variability of phytoplasma associated with few ornamental crop species in Uttar Pradesh, India

Abstract The economic importance of ornamentals has been advancing significantly in many countries due to continuous international demand. Like other crops, ornamental plants are also affected by a number of pathogens and the phytoplasmas diseases are equally important group of pathogens which is responsible for damaging the different ornamental plant species and thereby affecting their market value. In the present investigation, total 24 symptomatic leaf samples of 8 ornamental plant species (C. roseus, R. rubiginosa, C. variegatum, Z. elegans, J. gendurusa, T. erecta, H. rosa sinensis, J. sambrac) were analyzed which were found positive in nested PCR assays with R16F2n/R16R2 primers. The phytoplasma associated with ornamental plant species collected from different districts of UP in the present investigation are belongs to 16Sr I, II, VI and XIV group.
Firm Value and Pyramidal Structures: New Evidence for Family Firms

Abstract In this paper, we analyze what effects separating ownership and control have on the performance of a sample of 99 Chilean family-controlled firms for the period 2001–2014. Our results show an inverse U-shaped relationship between voting rights and cash flow rights divergence and firm value. This result suggests that excessive divergence of rights makes the firm’s value decline and can aggravate potential conflicts of interest inside family firms. We also find a positive moderating effect of business group affiliation, which highlights the ability of business groups to attenuate the negative impact of separating rights, particularly at high levels. We also find that family CEOs exert a beneficial effect on family firm performance at lower levels of divergence of rights, but that said effect disappears as the divergence of rights increases, suggesting that, when in control, family shareholders can ensure entrenchment by installing family member CEOs.
Mitochondrial plasticity supports proliferative outgrowth and invasion of ovarian cancer spheroids during adhesion

Background Ovarian cancer cells aggregate during or after exfoliation from the primary tumor to form threedimensional spheroids. Spheroid formation provides a survival advantage during peritoneal dissemination in nutrient and oxygen-depleted conditions which is accompanied by a suppressed metabolic phenotype and fragmented mitochondria. Upon arrival to their metastatic sites, spheroids adhere to peritoneal organs and transition to a more epithelial phenotype to support outgrowth and invasion. In this study, we investigated the plasticity of mitochondrial morphology, dynamics, and function upon adhesion. Methods Using our slow-developing (MOSE-L) and fast-developing (MOSE-LTICv) ovarian cancer models, we mimicked adhesion and reoxygenation conditions by plating the spheroids onto tissue culture dishes and changing culture conditions from hypoxia and low glucose to normoxia with high glucose levels after adhesion. We used Western Blot, microscopy and Seahorse analyses to determine the plasticity of mitochondrial morphology and functions upon adhesion, and the impact on proliferation and invasion capacities. Results Independent of culture conditions, all spheroids adhered to and began to grow onto the culture plates. While the bulk of the spheroid was unresponsive, the mitochondrial morphology in the outgrowing cells was indistinguishable from cells growing in monolayers, indicating that mitochondrial fragmentation in spheroids was indeed reversible. This was accompanied by an increase in regulators of mitobiogenesis, PGC1a, mitochondrial mass, and respiration. Reoxygenation increased migration and invasion in both cell types but only the MOSE-L responded with increased proliferation to reoxygenation. The highly aggressive phenotype of the MOSE-LTICv was characterized by a relative independence of oxygen and the preservation of higher levels of proliferation, migration and invasion even in limiting culture conditions but a higher reliance on mitophagy. Further, the outgrowth in these aggressive cells relies mostly on proliferation while the MOSE-L cells both utilize proliferation and migration to achieve outgrowth. Suppression of proliferation with cycloheximide impeded aggregation, reduced outgrowth and invasion via repression of MMP2 expression and the flattening of the spheroids. Discussion Our studies indicate that the fragmentation of the mitochondria is reversible upon adhesion. The identification of regulatory signaling molecules and pathways of these key phenotypic alterations that occur during primary adhesion and invasion is critical for the identification of druggable targets for therapeutic intervention to prevent aggressive metastatic disease.
A study of corneal changes –endothelial cell density (ECD) and central corneal thickness (CCT) in Type -2 DM in relation to Hba1c levels and compare it with healthy individuals

Background: Diabetes in India is very common chronic systemic disease which causes wide range of ocular complications. Besides, diabetic retinopathy, patients with diabetes are prone to developing corneal endothelial damage, corneal oedema, epithelial changes like keratoepitheliopathy in the form of recurrent corneal erosions, persistent epithelial defects, and superficial keratitis. Objectives: The aim of this study was to measure the central corneal thickness and ECD in type -2 DM in relation to Hba1c levels and compare with healthy individuals of same age group. Material and Methods: It was a hospital based, prospective case-control study. A total of 120 patients, 50-70 yrs of age, participated in the study, of whom 60 were diabetic type 2 on oral hypoglycemic already established from medicine department and 60 healthy individuals of same age group attended eye OPD were taken after taking Consents from patients at medical college in Uttarakhand, and approval from ethical committee. Study group was divided into two groups – diabetic type 2 (with Hba1c 7) and healthy individuals. After thorough ocular examination include slit lamp and fundus examination, the central corneal thickness and endothelial cell count (ECD) was measured using specular/ pachymetry nidek machine. Exclusion criteria was any corneal pathology, ocular surgery, trauma any other systemic illness, insulin dependent, on topical drops. Results: Mean CCT was thicker in diabetic group (575.53μm) when compared to non-diabetic group (560.40μm). The difference between the 2 groups was significant (p7 and duration of diabetes. Keywords: Central Corneal thickness1, Pachymetry3, Specularmicroscopy4, Endothelial Cell Density2
Nutrient status of cattle grazing systems in the western brazilian amazon

Abstract Low-input cultivated pastures to feed cattle have dominated land use after forest clearing for decades in the western Brazilian Amazon. This study was undertaken to help understand the inherent nutrient supply dynamics underwriting cattle performance on three farms in the state of Acre. We assessed soil chemical and physical properties associated over time with different land uses following forest clearing. This information permitted specifying a conceptual model of nutrient stocks and flows under the observed grazing system, which produced insights about the dynamics of soil nutrient degradation. Above ground forage mass, topsoil nutrient concentrations and soil bulk density were measured. Land covers were Brachiaria spp. grasses, a grass-Pueraria phaseoloides mix, cropland and forest. Most soil nutrient parameters initially decreased after clearing, gradually recovering over time with grass-only pastures; however, 20 yr-old pastures had 20% less forage mass. Most pasture system nutrients on these farms resided in topsoil and roots, where large stocks of mature forage supported soil fertility with recycled nutrients from litter. Estimates of partial topsoil nutrient balances were negative. This suggested that corresponding nutrient stocks and the accumulation of forage mass were probably maintained primarily through the sum of inflows from cattle excreta, the subsoil, soil organic matter, and litter mineralization with scant input of commercial fertilizer. Therefore, herd management to increase animal system productivity via higher stocking rates on vegetatively younger forage requires monitoring of nutrient stocks and flows and fertilization that assures replenishment of the nutrients extracted. Otherwise, rapid depletion of soil nutrient stocks will lead to system degradation and failure.
Foreign Trade, FDI and the Upgrading of Regional Industrial Structure in China: Based on Spatial Econometric Model

The upgrading of industrial structure is the core means of coordinating economic development and environment protection. Its spatial agglomeration can also reduce environmental pollution partly. The upgrading of China’s industrial structure has become an important issue concerned by the whole society. To better understand this issue, based on the provincial data of China (1997–2017), this paper strives to explore the spatial effects of foreign trade and foreign direct investment (FDI) on the upgrading of China’s regional industrial structure by constructing the weight matrix of economic distance, and by introducing the spatial autocorrelation analysis method and spatial panel econometric model. The results show that: 1. The Moran’s I index of China’s import, export, FDI, and industrial structure upgrading has passed the 5% significance level test, displaying remarkable spatial agglomeration characteristics. 2. Foreign trade and FDI are important driving factors to upgrade China’s industrial structure. 3. Foreign trade has a significant spatial spillover effect. Imports and exports can not only promote the upgrading of local industrial structure, but also radiate to other regions, promote or inhibit the development of its industry, and further affect the national data. 4. The spatial spillover effect of FDI is not significant. Finally, some policy suggestions are put forward.
Beat-to-beat blood-pressure measurements applied in studies on mental workload

Heart rate variability diminishes during mental task performance. This decrease can be related to a change in control of the autonomic nervous system of blood pressure. This change in sympathetic/parasympathetic balance might be caused by a decrease in baroreflex sensitivity. - To study the characteristics of the baroreflex, blood pressure has to be assessed beat-to-beat. Continuously monitored blood pressure can provide the beat-to-beat values for computing spectral measures of blood pressure, and the baroreflex sensitivity. - The objective of this paper is to show that the effects of mental workload on blood pressure in a series of experiments are very consistent, although different methods were used to measure blood pressure continuously (Intra-arterial, FIN.A.PRES model 3 and 5, Ohmeda 2300). We selected one or two similar tasks from four experiments with small differences in task characteristics. - The cardiovascular effects of mental workload are characterized by a decrease in inter-brat interval, heart rate variability, blood pressure variability, and baroreflex sensitivity, and an increase of blood pressure. The blood pressure increase and the BRS decrease was larger for the more effortful tasks within the experiments. These effects are found in spite of the different methods of blood pressure measurements. - We conclude that the FIN.A. PRES devices are very well applicable in our research, where rest-task comparisons play a major role. The task effects in intra-arterially measured blood pressure are very well reproduced by FIN.A. PRES models.
Targeting type I interferons in systemic lupus erythematous

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with systemic clinical manifestations including, but not limited to, rash, inflammatory arthritis, serositis, glomerulonephritis, and cerebritis. Treatment options for SLE are expanding and the increase in our understanding of the immune pathogenesis is leading to the development of new therapeutics. Autoantibody formation and immune complex formation are important mediators in lupus pathogenesis, but an important role of the type I interferon (IFN) pathway has been identified in SLE patients and mouse models of lupus. These studies have led to the development of therapeutics targeting type I IFN and related pathways for the treatment of certain manifestations of SLE. In the current narrative review, we will discuss the role of type I IFN in SLE pathogenesis and the potential translation of these data into strategies using type I IFN as a biomarker and therapeutic target for patients with SLE.
Double-stranded RNA bending by AU-tract sequences

Sequence-dependent structural deformations of the DNA double helix (dsDNA) have been extensively studied, where adenine tracts (A-tracts) provide a striking example for global bending in the molecule. In contrast to dsDNA, much less is known about how the nucleotide sequence affects bending deformations of double-stranded RNA (dsRNA). Using all-atom microsecond long molecular dynamics simulations we found a sequence motif consisting of alternating adenines and uracils, or AU-tracts, that bend the dsRNA helix by locally compressing the major groove. We experimentally tested this prediction using atomic force microscopy (AFM) imaging of long dsRNA molecules containing phased AU-tracts. AFM images revealed a clear intrinsic bend in these AU-tracts molecules, as quantified by a significantly lower persistence length compared to dsRNA molecules of arbitrary sequence. The bent structure of AU-tracts here described might play a role in sequence-specific recognition of dsRNAs by dsRNA-interacting proteins or impact the folding of RNA into intricate tertiary and quaternary structures.
Assessing the Relationship Between Nontraditional Factors and Academic Entitlement

The current study explores the intersection of two trends of interest in higher education: reported increases in academic entitlement (AE) and increases in the proportion of students considered nontraditional. AE has shown to have negative effects in the classroom and for students. Based on reports from educators, levels of AE may be lower for nontraditional students. The current study sought to understand the level of AE in nontraditional students, compare AE levels with traditional students, and investigate if specific nontraditional factors have larger impacts on AE. Four hundred and twenty-nine participants were assessed for nontraditional factors and their current level of AE. Nontraditional students were found to have lower levels of AE than traditional students, having more nontraditional factors predicted lower AE, and AE was found to vary within nontraditional grouping levels. Additionally, age and hours worked were found to be individual factors that best predicted AE levels.
Hemostasis in Cardiac Surgery: How We Do it with Limited Resources

Hemostasis in cardiac surgery is still a severe problem for surgeons. Blood and its products are the most valuable at the same time dangerous arms of surgeons. Industries produced many biological or non-biological products, which increase the cost of operations, are available for this issue. Decision making and producing solutions must be the most important properties of a cardiac surgeon. In any condition and resources, true strategy and patience will bring the success. Antiaggregants and anticoagulants are widely used agents, and in emergency or early cases, surgeons have to operate these patients. Both groups of drugs are growing, and in an emergency position, it is hard to know which drugs the patient using or given and what kind of medical status he/she has. For example non vitamin-K oral anticoagulants newer drugs and not known so much except cardiologists and cardiovascular surgeons. Simple solutions may have better results. Of course, in some conditions, urgent consultation can solve the problem. Cardiac surgeons have to figure out the problem by using their experience and surgical materials. Working as a team is a big advantage, more than one surgeon, experienced operation nurses and closer follow up in intensive care unit.
Accuracy Improvement of UNet Based on Dilated Convolution

Though previous approach for the satellite image semantic segmentation task has already achieved reliable performance across some different benchmarks, there are still some limitations for the existing methods when faced with the scenarios of the high-resolution images. In this paper, we propose a powerful dilated convolution module and successfully apply it into our improved UNet network structure. The dilated convolution module can directly expand the receptive field of the network without reducing the resolution. Experiments on DeepGlobe Road Extraction Task have shown that the proposed method in this work can achieve the mIoU score of 63.72%, which significantly outperforms the original algorithm.
Role of adrenergic receptors in shock

Shock is a severe, life-threatening medical condition with a high mortality rate worldwide. All four major categories of shock (along with their various subtypes)—hypovolemic, distributive, cardiogenic, and obstructive, involve a dramatic mismatch between oxygen supply and demand, and share standard features of decreased cardiac output, reduced blood pressure, and overall hypoperfusion. Immediate and appropriate intervention is required regardless of shock type, as a delay can result in cellular dysfunction, irreversible multiple organ failure, and death. Studies have shown that dysfunction and downregulation of adrenergic receptors (ARs) are often implicated in these shock conditions; for example, their density is shown to be decreased in hypovolemic and cardiogenic shock, while their reduced signaling in the brain and vasculature decrease blood perfusion and oxygen supply. There are two main categories of ARs, α, and β, each with its subtypes and distributions. Our group has demonstrated that a dose of . 02 mg/kg body wt of centhaquine (CQ) specifically activates α2B ARs on venous circulation along with the central α2A ARs after hypovolemic/hemorrhagic shock. Activating these receptors by CQ increases cardiac output (CO) and reduces systemic vascular resistance (SVR), with a net increase in blood pressure and tissue perfusion. The clinical trials of CQ conducted by Pharmazz Inc. in India have demonstrated significantly improved survival in shock patients. CQ improved blood pressure and shock index, indicating better blood circulation, and reduced lactate levels in the blood compared to in-use standard resuscitative agents. After successful clinical trials, CQ is being marketed as a drug (Lyfaquin®) for hypovolemic/hemorrhagic shock in India, and United States FDA has approved the phase III IND application. It is anticipated that the phase III trial in the United States will begin in 2023. Thus, we have demonstrated that α2 ARs could be suitable targets for treating or managing hypovolemic/hemorrhagic shock. Further understanding of ARs in shock would help find new potential pharmacological targets.
Magnetic Resonance Image Segmentation Based on Multi-Scale Convolutional Neural Network

The incidence of nervous system and soft tissue is getting higher, and nuclear magnetic resonance is the preferred method of examination and is widely used. The segmentation of brain magnetic resonance (MR) images is the key to the subsequent operations such as three-dimensional reconstruction, quantitative analysis of normal tissues and diseased tissues. The accuracy of image segmentation is critical in the doctor’s assessment with the location, shape, and size of the lesion tissue, as well as the determination of the disease and the correct diagnosis plan. The results of this study indicate that the multi-scale convolutional neural network (MSCNN) model can segment brain tumors accurately and effectively. Through multi-scale input, this paper overcomes the need to select specific input scales according to the size of the tumor, accommodate more neighborhood information from various angles, and adapt to different tumor sizes, thus improving the segmentation accuracy of brain tumors. Based on the same accuracy, the segmentation speed is accelerated to ensure the real-time segmentation further. This method can effectively segment the brain lesion tissue in the nuclear magnetic resonance image, which improves the generalization ability. It can be used for identifying the brain lesion tissue of the nuclear magnetic resonance medical image.
Attitudes and practices of medical students regarding video-games: should community medicine educationists get serious about serious games

Background: Present medicos belong to a generation called ‘Millennials’ or ‘Net Generation’. They spend less time reading, and are more comfortable in image-rich environments provided by New Media. The objective of the study is to identify knowledge, attitudes and practices of medical students regarding video-games, with the aim of prompting community medicine teachers to consider serious games as a teaching-learning tool . Methods: The study was conducted among undergraduate medical students who self-administered a structured questionnaire eliciting their practices and attitudes regarding video-games, perceptions regarding impact of video-gaming on their academic performances and acceptability of serious games as a learning tool in community medicine. Results: A total of 255 medical students participated in the study, out of which 242 (94.9%) were current video-gamers. The students started playing video-games at a mean age of 11.72+3.63 years. Mobile phones were the commonest platform for video-gaming. The median duration of video-gaming was 150 minutes/week, with semi-inter-quartile range of 255 minutes. 57.4% of students reported that video-games helped them relax, while 26% felt that video-gaming increased their skills. The study revealed that 43.6% students were aware of serious games and 22.7% had used them as a learning tool in last three months. Moreover, about 95% of medicos welcomed learning of community medicine through serious games. Conclusions: The study reveals that contemporary medical students are spending considerable time playing video-games. It also shows that the learner is willing to learn community medicine through serious games. The study prompts community medicine educationists to consider serious games as a teaching-learning tool.