Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and Efficacy of Stereotactic Body Radiation Therapy for Locoregional Recurrences After Prior Chemoradiation for Advanced Esophageal Carcinoma

Purpose: This study aimed to investigate the feasibility of stereotactic body radiation therapy (SBRT) as salvage therapy for locally recurrent esophageal cancer. We hypothesized that SBRT would provide durable treated tumor control with minimal associated toxicity in patients with progressive disease after definitive radiation, chemotherapy, and surgical resection. Methods: This single-institution retrospective study assessed outcomes in patients who received SBRT for locoregional failure of esophageal cancer after initial curative-intent treatment. Only patients who had received neoadjuvant chemoradiation (≥41.4 Gy) for esophageal cancer were selected. Subsequent surgical resection was optional but institutional follow-up by an oncologist was required. The primary endpoints of this study were gastrointestinal and constitutional toxicity, scored with the Common Terminology Criteria for Adverse Events v5.0. A secondary outcome, treated-tumor control, was assessed with RECIST v1.1. Results: Nine patients (11 locoregional recurrences) treated with SBRT were reviewed, with a median follow-up time of 10.5 months. Most patients initially presented with T3 (88.9%), N1 (55.6%), moderately differentiated (66.7%) adenocarcinoma (88.9%), and had received a median 50.4 Gy delivered over 28 fractions with concurrent carboplatin/paclitaxel chemotherapy followed by surgical resection. Median time to recurrence was 16.3 months. Median total dose delivered by SBRT was 27.5 Gy (delivered in five fractions). Two patients experienced acute grade 1 fatigue and vomiting. No patient experienced grade 3 or higher toxicity. One patient experienced failure in the SBRT treatment field at 5.8 months after treatment and six patients developed distant failure. The median progression-free survival time for SBRT-treated tumors was 5.0 months, and median overall survival time was 12.9 months. Conclusions: This single-institution study demonstrated the feasibility of SBRT for locoregional recurrence of esophageal cancer with minimal treatment-related toxicity and high rates of treated tumor control. Prospective studies identifying ideal salvage SBRT candidates for locoregional failure as well as validating its safety are needed.
Supraphysiological Levels of Testosterone Induce Vascular Dysfunction via Activation of the NLRP3 Inflammasome

Background: Both supraphysiological and subphysiological testosterone levels are associated with increased cardiovascular risk. Testosterone consumption at supraphysiological doses has been linked to increased blood pressure, left ventricular hypertrophy, vascular dysfunction, and increased levels of inflammatory markers. Activation of the NLRP3 inflammasome contributes to the production of proinflammatory cytokines, leading to cardiovascular dysfunction. We hypothesized that supraphysiological levels of testosterone, via generation of mitochondrial reactive oxygen species (mROS), activates the NLRP3 inflammasome and promotes vascular dysfunction. Methods: Male, 12 week-old C57Bl/6J (WT) and NLRP3 knockout (NLRP3−/−) mice were used. Mice were treated with testosterone propionate [TP (10 mg/kg) in vivo] or vehicle for 30 days. In addition, vessels were incubated with testosterone [Testo (10−6 M, 2 h) in vitro]. Testosterone levels, blood pressure, vascular function (thoracic aortic rings), pro-caspase-1/caspase-1 and interleukin-1β (IL-1β) expression, and generation of reactive oxygen species were determined. Results: Testosterone increased contractile responses and reduced endothelium-dependent vasodilation, both in vivo and in vitro. These effects were not observed in arteries from NLRP3−/− mice. Aortas of TP-treated WT mice (in vivo), as well as aortas from WT mice incubated with testo (in vitro), exhibited increased mROS levels and increased caspase-1 and IL-1β expression. These effects were not observed in arteries from NLRP3−/− mice. Flutamide [Flu, 10−5 M, androgen receptor (AR) antagonist], carbonyl cyanide m-chlorophenyl hydrazone (CCCP, 10−6 M, mitochondrial uncoupler) and MCC950 (MCC950, 10−6 M, a NLRP3 receptor inhibitor) prevented testosterone-induced mROS generation. Conclusion: Supraphysiological levels of testosterone induce vascular dysfunction via mROS generation and NLRP3 inflammasome activation. These events may contribute to increased cardiovascular risk.
PD-L1 Is Expressed and Promotes the Expansion of Regulatory T Cells in Acute Myeloid Leukemia

Intratumoral accumulation of CD4+CD25+Foxp3+ regulatory T (Treg) cells occurs in acute myeloid leukemia (AML), but little is known about the role of tumor cells themselves in this process. Here, we showed that an immune checkpoint PD-L1 expressed by AML cells promoted the conversion and expansion of Treg cells sustaining high expression of Foxp3 and PD-1 as well as a suppressive function. Furthermore, an AML cell line HEL overexpressed PD-L1 promoted the conversion and expansion of Treg cells and CD4+PD-1+Foxp3+ T (PD-1+Treg) cells from the conventional CD4+ T cells. CD4+CD25highPD-1+ T cells secreted more IL-10 production than CD4+CD25highPD-1− T cells. IL-35, another cytokine secreted by Treg cells, promoted the proliferation of HL-60 cells and enhanced chemoresistance to cytarabine. Blockade of PD-1 signaling using anti-PD-L1 antibody dramatically impaired the generation of Treg cells and sharply retarded the progression of a murine AML model injected with C1498 cells. The frequency of intratumoral PD-1+ Treg cells was capable of predicting patient survival in patients with AML. In conclusion, our data suggest that PD-L1 expression by AML cells may directly drive Treg cell expansion as a mechanism of immune evasion and the frequency of PD-1+ Treg cells is a potential prognostic predictor in patients with AML.
Use of a Rolled-rye Cover Crop for Weed Suppression in No-Till Soybeans

Abstract Cover crop management with a roller/crimper might reduce the need for herbicide. Weed suppression from a rolled cereal rye cover crop was compared to no cover crop with and without postemergence herbicide application in no-till soybean. The experiment was designed as a two-way factorial with rye termination and soybean planting date as the first factor and weed control treatment as the second. Cereal rye was drill-seeded in late September and managed using glyphosate followed by a roller/crimper in the spring. Soybean was no-till seeded after rolling and glyphosate was applied postemergence about 6 wk after planting to half the plots. Rye biomass doubled when delaying rye kill by 10 to 20 d. Weed density and biomass were reduced by the rye cover crop in all site–location combinations except one, but delaying rye kill and soybean planting date only reduced both weed density and biomass at a single location. The cover crop mulch provided weed control similar to the postemergence herbicide in two of four locations. Treatments did not affect soybean grain yield in 2007. In 2008, yield at Landisville with rye alone was equal to those yields receiving the postemergence herbicide, whereas at Rock Springs, it was equivalent or less. The net added cost of a rye cover crop was $123 ha−1 with or $68.50 ha−1 without a postemergence herbicide application. A rolled-rye cover crop sometimes provided acceptable weed control, but weed control alone did not justify the use of the cover crop. The potential for reduced herbicide use and other ecosystem services provided by a cover crop justify further refinement and research in this area. Nomenclature: Glyphosate; rye, Secale cereale L. ; soybean, Glycine max L.
Statistical Learning Signals for Complex Visual Images in Macaque Early Visual Cortex

Animals of several species, including primates, learn the statistical regularities of their environment. In particular, they learn the temporal regularities that occur in streams of visual images. Previous human neuroimaging studies reported discrepant effects of such statistical learning, ranging from stronger occipito-temporal activations for sequences in which image order was fixed, compared with sequences of randomly ordered images, to weaker activations for fixed-order sequences compared with sequences that violated the learned order. Several single-unit studies in macaque monkeys reported that after statistical learning of temporal regularities, inferior temporal (IT) neurons show reduced responses to learned fixed-order sequences of visual images compared with random or mispredicted sequences. However, it is unknown how other macaque brain areas respond to such temporal statistical regularities. To address this gap, we exposed rhesus monkeys (Macaca mulatta) to two types of sequences of complex images. The “regular” sequences consisted of a continuous stream of quartets, and within each quartet, the image order was fixed. The quartets themselves were displayed, uninterrupted, in a random order. The same monkeys were exposed to sequences of other images having a pseudorandomized order (“random” sequence). After exposure, both monkeys were scanned with functional MRI (fMRI) using a block design with three conditions: regular sequence, random sequence, and fixation-only blocks. A whole-brain analysis showed a reduced activation in mainly the occipito-temporal cortex for the regular compared to the random sequences. Marked response reductions for the regular sequence were observed in early extrastriate visual cortical areas, including area V2, despite the use of rather complex images of animals. These data suggest that statistical learning signals are already present in early visual areas of monkeys, even for complex visual images. These monkey fMRI data are in line with recent human fMRI studies that showed a reduced activation in early visual areas for predicted compared with mispredicted complex images.
Oxidation-Specific Epitopes (OSEs) Dominate the B Cell Response in Murine Polymicrobial Sepsis

In murine abdominal sepsis by colon ascendens stent peritonitis (CASP), a strong increase in serum IgM and IgG antibodies was observed, which reached maximum values 14 days following sepsis induction. The specificity of this antibody response was studied in serum and at the single cell level using a broad panel of bacterial, sepsis-unrelated as well as self-antigens. Whereas an antibacterial IgM/IgG response was rarely observed, studies at the single-cell level revealed that IgM antibodies, in particular, were largely polyreactive. Interestingly, at least 16% of the IgM mAbs and 20% of the IgG mAbs derived from post-septic mice showed specificity for oxidation-specific epitopes (OSEs), which are known targets of the innate/adaptive immune response. This identifies those self-antigens as the main target of B cell responses in sepsis.
Syndecan-4–/– Mice Have Smaller Muscle Fibers, Increased Akt/mTOR/S6K1 and Notch/HES-1 Pathways, and Alterations in Extracellular Matrix Components

Background Extracellular matrix (ECM) remodeling is essential for skeletal muscle development and adaption in response to environmental cues such as exercise and injury. The cell surface proteoglycan syndecan-4 has been reported to be essential for muscle differentiation, but few molecular mechanisms are known. Syndecan-4–/– mice are unable to regenerate damaged muscle, and display deficient satellite cell activation, proliferation, and differentiation. A reduced myofiber basal lamina has also been reported in syndecan-4–/– muscle, indicating possible defects in ECM production. To get a better understanding of the underlying molecular mechanisms, we have here investigated the effects of syndecan-4 genetic ablation on molecules involved in ECM remodeling and muscle growth, both under steady state conditions and in response to exercise. Methods Tibialis anterior (TA) muscles from sedentary and exercised syndecan-4–/– and WT mice were analyzed by immunohistochemistry, real-time PCR and western blotting. Results Compared to WT, we found that syndecan-4–/– mice had reduced body weight, reduced muscle weight, muscle fibers with a smaller cross-sectional area, and reduced expression of myogenic regulatory transcription factors. Sedentary syndecan-4–/– had also increased mRNA levels of syndecan-2, decorin, collagens, fibromodulin, biglycan, and LOX. Some of these latter ECM components were reduced at protein level, suggesting them to be more susceptible to degradation or less efficiently translated when syndecan-4 is absent. At the protein level, TRPC7 was reduced, whereas activation of the Akt/mTOR/S6K1 and Notch/HES-1 pathways were increased. Finally, although exercise induced upregulation of several of these components in WT, a further upregulation of these molecules was not observed in exercised syndecan-4–/– mice. Conclusion Altogether our data suggest an important role of syndecan-4 in muscle development.
Cutaneous manifestations of diabetes mellius: a clinico epidemiological study

<p class="abstract"><strong>Background:</strong> Diabetes mellitus is one of the commonest non communicable diseases seen all over the world, constituting 49% from India, i.e., 72 million patients according to the Indian Council of Medical Research. The aim of the study was to study the various skin manifestations in diabetic patients and to correlate them with glycemic levels. </p><p class="abstract"><strong>Methods:</strong> Patients for the study were chosen among those who were on treatment for diabetes mellitus and presented to the skin department with various cutaneous manifestations. <strong></strong></p><p class="abstract"><strong>Results:</strong> Infections were commonest cutaneous manifestations in both type 1 and type 2. Among infections, fungal infections were commoner followed by bacterial infections. Among house wives, the commoner was candidal dermatosis intertrigo-toe/finger cleft followed by chronic paronychia. Among bacterial infections, erythrasma was commonly followed by pyoderma. Among pyodermas, furunculosis was common. Most common associated dermatoses were acanthosis nigricans and acrochordons. Treatment-related manifestations were not found. </p><p><strong>Conclusions:</strong> In type 2 diabetic patients, infections were commonly followed by acanthosis nigricans, acrochordons, and generalized pruritus. Glycemic levels were higher in those with candidiasis and also with pyodermas. </p>
Protective Mechanisms of Quercetin Against Myocardial Ischemia Reperfusion Injury

Quercetin has attracted more attention in recent years due to its protective role against ischemia/reperfusion injury. Quercetin can alleviate oxidative stress injury through the inhibition of NADPH oxidase and xanthine oxidase, blockage of the Fenton reaction, and scavenging of reactive oxygen species. Quercetin can also exert anti-inflammatory and anti-apoptotic effects by reducing the response to inflammatory factors and inhibiting cell apoptosis. Moreover, it can induce vasodilation effects through the inhibition of endothelin-1 receptors, the enhancement of NO stimulation and the activation of the large-conductance calcium-activated potassium channels. Finally, Quercetin can also antagonize the calcium overload. These multifaceted activities of Quercetin make it a potential therapeutic alternative for the treatment of ischemia/reperfusion injury.
Identifying Individuals at High Risk for Permanent Disability From Depression and Anxiety

Mental illnesses, among which depression and anxiety are most common, are the leading cause for permanent disability. It is of interest to know what case characteristics determine if a person returns to the work force in spite of mental illness to tailor specific interventions. So far, there has been little research into this field. In the present study a sample of 202 workers who had permanent disability due to depression/anxiety were followed-up on. 22% started some kind of work during follow-up in a period of 30 to 75 months. Logistic regression analyses showed that quick progression into disability, short period of disability, younger age, adequacy of income replacement through insurance benefits and no previous disability predicted return to work. These findings also allow to identify individuals at high risk for progression into permanent disability that can benefit from supporting interventions.
Reactions to Problematic Internet Use Among Adolescents: Inappropriate Physical and Mental Health Perspectives

Although numerous studies have examined the factors influencing problematic Internet use (PIU), few studies have investigated the interactions between inappropriate physical and mental health (e.g., cyberbullying, Internet pornography, and Internet fraud) as factors facilitating PIU and examined the moderating effect of community bond. Thus, this study analyzed the moderating role of community bond in the relationship between cyberbullying, Internet pornography, Internet fraud, and PIU. Using a cross-sectional survey, adolescents were surveyed through self-report questionnaires. A total of 5,211 responses were received from participant students at 60 senior high schools in Taiwan. Statistical analyses were performed using structural equation modeling. The results indicated that cyberbullying, Internet pornography, Internet fraud, and community bond have significant positive effects on PIU. Community bond has a significant moderating effect in the relationship between cyberbullying, Internet fraud, and the PIU of adolescents. Parental Internet attitude and behavior were found to significantly moderate the relationship between inappropriate physical and mental health, community bond, and PIU. The results suggest that public health and education policies should focus more on adolescents who require additional assistance. Furthermore, school policies could be more informed in regard to relevant psychosocial variables and patterns of Internet use. Finally, this study may serve as a reference for parents, schools, and government education authorities.
Open Problem: Fast and Optimal Online Portfolio Selection

Online portfolio selection has received much attention in the COLT community since its introduction by Cover, but all state-of-the-art methods fall short in at least one of the following ways: they are either i) computationally infeasible; or ii) they do not guarantee optimal regret; or iii) they assume the gradients are bounded, which is unnecessary and cannot be guaranteed. We are interested in a natural follow-the-regularized-leader (FTRL) approach based on the log barrier regularizer, which is computationally feasible. The open problem we put before the community is to formally prove whether this approach achieves the optimal regret. Resolving this question will likely lead to new techniques to analyse FTRL algorithms. There are also interesting technical connections to self-concordance, which has previously been used in the context of bandit convex optimization.
Evaluation of the TRMM Product for Monitoring Drought over Paraíba State, Northeastern Brazil: A Statistical Analysis

Drought is a natural phenomenon that originates from the absence of precipitation over a certain period and is capable of causing damage to societal development. With the advent of orbital remote sensing, rainfall estimates from satellites have appeared as viable alternatives to monitor natural hazards in ungauged basins and complex areas of the world; however, the accuracies of these orbital products still need to be verified. Thus, this work aims to evaluate the performance of Tropical Rainfall Measuring Mission (TRMM) satellite rainfall estimates in monitoring the spatiotemporal behavior of droughts at multiple temporal scales over Paraíba State based on the standardized precipitation index (SPI) over 20 years (1998–2017). For this purpose, rainfall data from 78 rain gauges and 187 equally spaced TRMM cell grids throughout the region are used, and accuracy analyses are performed at the single-gauge level and in four mesoregions at eight different time scales based on 11 statistical metrics calculations divided into three different categories. The results show that in the mesoregions close to the coast, the satellite-based product is less accurate in capturing the drought behavior regardless of the evaluated statistical metrics. At the temporal scale, the TRMM is more accurate in identifying the pattern of medium-term droughts; however, there is considerable spatial variation in the accuracy of the product depending on the performance index. Therefore, it is concluded that rainfall estimates from the TRMM satellite are a valuable source of data to identify drought behavior in a large part of Paraíba State at different time scales, and further multidisciplinary studies should be conducted to monitor these phenomena more accurately based on satellite data.
LiDAR-Aided Interior Orientation Parameters Refinement Strategy for Consumer-Grade Cameras Onboard UAV Remote Sensing Systems

Unmanned aerial vehicles (UAVs) are quickly emerging as a popular platform for 3D reconstruction/modeling in various applications such as precision agriculture, coastal monitoring, and emergency management. For such applications, LiDAR and frame cameras are the two most commonly used sensors for 3D mapping of the object space. For example, point clouds for the area of interest can be directly derived from LiDAR sensors onboard UAVs equipped with integrated global navigation satellite systems and inertial navigation systems (GNSS/INS). Imagery-based mapping, on the other hand, is considered to be a cost-effective and practical option and is often conducted by generating point clouds and orthophotos using structure from motion (SfM) techniques. Mapping with photogrammetric approaches requires accurate camera interior orientation parameters (IOPs), especially when direct georeferencing is utilized. Most state-of-the-art approaches for determining/refining camera IOPs depend on ground control points (GCPs). However, establishing GCPs is expensive and labor-intensive, and more importantly, the distribution and number of GCPs are usually less than optimal to provide adequate control for determining and/or refining camera IOPs. Moreover, consumer-grade cameras with unstable IOPs have been widely used for mapping applications. Therefore, in such scenarios, where frequent camera calibration or IOP refinement is required, GCP-based approaches are impractical. To eliminate the need for GCPs, this study uses LiDAR data as a reference surface to perform in situ refinement of camera IOPs. The proposed refinement strategy is conducted in three main steps. An image-based sparse point cloud is first generated via a GNSS/INS-assisted SfM strategy. Then, LiDAR points corresponding to the resultant image-based sparse point cloud are identified through an iterative plane fitting approach and are referred to as LiDAR control points (LCPs). Finally, IOPs of the utilized camera are refined through a GNSS/INS-assisted bundle adjustment procedure using LCPs. Seven datasets over two study sites with a variety of geomorphic features are used to evaluate the performance of the developed strategy. The results illustrate the ability of the proposed approach to achieve an object space absolute accuracy of 3–5 cm (i.e., 5–10 times the ground sampling distance) at a 41 m flying height.
Protohydra leuckarti near Plymouth

A new location for Protohydra leuckarti is reported near Plymouth at Millbrook Lake (Tamar Estuary). To place this finding in context, notes follow on a familiar habitat of this species in the White Sea, and on the general ecology and distribution of Protohydra and its enigmatic phylogeny.