Miracle-dz/UniFAR-FTUs huggingface dataset:
Malnutrition Alters the Innate Immune Response and Increases Early Visceralization following Leishmania donovani Infection

ABSTRACT Malnutrition is a risk factor for the development of visceral leishmaniasis. However, the immunological basis for this susceptibility is unknown. We have developed a mouse model to study the effect of malnutrition on innate immunity and early visceralization following Leishmania donovani infection. Three deficient diets were studied, including 6, 3, or 1% protein; these diets were also deficient in iron, zinc, and calories. The control diet contained 17% protein, was zinc and iron sufficient, and was provided ab libitum. Three days after infection with L. donovani promastigotes, the total extradermal (lymph nodes, liver, and spleen) and skin parasite burdens were equivalent in the malnourished (3% protein) and control mice, but in the malnourished group, a greater percentage (39.8 and 4.0%, respectively;P = 0.009) of the extradermal parasite burden was contained in the spleen and liver. The comparable levels of parasites in the footpads in the two diet groups and the higher lymph node parasite burdens in the well-nourished mice indicated that the higher visceral parasite burdens in the malnourished mice were not due to a deficit in local parasite killing but to a failure of lymph node barrier function. Lymph node cells from the malnourished, infected mice produced increased levels of prostaglandin E2(PGE2) and decreased levels of interleukin-10. Inducible nitric oxide synthase activity was significantly lower in the spleen and liver of the malnourished mice. Thus, malnutrition causes a failure of lymph node barrier function after L. donovani infection, which may be related to excessive production of PGE2and decreased levels of IL-10 and nitric oxide.
Geographic characteristics of sable (Martes zibellina) distribution over time in Northeast China

Abstract Understanding historical context can help clarify the ecological and biogeographic characteristics of species population changes. The sable (Martes zibellina) population has decreased dramatically in Northeast China since the l950s, and understanding the changes in its distribution over time is necessary to support conservation efforts. To achieve this goal, we integrated ecological niche modeling and historical records of sables to estimate the magnitude of change in their distribution over time. Our results revealed a 51.71% reduction in their distribution in 2000–2016 compared with the potential distribution in the 1950s. This reduction was related to climate change (Pearson's correlation: Bio1, −.962, p < .01; Bio2, −.962, p < .01; Bio5, .817, p < .05; Bio6, .847, p < .05) and human population size (−.956, p < .01). The sable population tended to migrate in different directions and elevations over time in different areas due to climate change: In the Greater Khingan Mountains, they moved northward and to lower elevations; in the Lesser Khingan Mountains, they moved northward; and in the Changbai Mountains, they move southward and to higher elevations. Active conservation strategies should be considered in locations where sable populations have migrated or may migrate to.
A parent‐directed intervention for addressing academic risk in Latino survivors of childhood leukemia: results of a pilot study

Laura Bava, Jemily Malvar, Richard Sposto, Maki Okada, Betty Gonzalez-Morkos, Lisl M. Schweers, Christopher Nuñez, Kathleen Ruccione, Ernest R. Katz and David R. Freyer* Survivorship and Supportive Care Program, Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, Los Angeles, CA, USA Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, Los Angeles, CA, USA Division of Hematology, Oncology and Blood and Marrow Transplantation, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
111In-Bevacizumab Imaging of Renal Cell Cancer and Evaluation of Neoadjuvant Treatment with the Vascular Endothelial Growth Factor Receptor Inhibitor Sorafenib

Clear cell renal cell cancer (ccRCC) prominently expresses vascular endothelial growth factor-A (VEGF-A), and new treatment strategies for renal cell cancer (RCC) aim at the inhibition of VEGF–VEGF receptor signaling. This study explores the ability of 111In-bevacizumab scintigraphy to depict RCC and to evaluate response to neoadjuvant treatment with sorafenib, a VEGF receptor inhibitor. Methods: The ability to depict RCC with 111In-bevacizumab scintigraphy was tested in 14 patients scheduled to undergo a tumor nephrectomy; of these, 9 RCC patients were treated in a neoadjuvant setting with sorafenib (400 mg orally twice a day). In the latter group, baseline and posttreatment 111In-bevacizumab scans were compared. The intratumoral distribution of 111In-bevacizumab was determined scintigraphically ex vivo in a 1-cm lamella of the resected tumorous kidney. Expression of VEGF-A, glucose transporter-1, carbonic anhydrase IX, α-smooth-muscle actin, and Ki67 was determined by immunohistochemistry and compared with the local concentration of 111In-bevacizumab. Additionally, the VEGF-A content in tumor samples was determined quantitatively by enzyme-linked immunosorbent assay. Results: In all 5 non–neoadjuvant-treated patients, preferential accumulation of 111In-bevacizumab was observed in the tumors. All ccRCC lesions with enhanced 111In-bevacizumab targeting expressed high levels of VEGF-A. Treatment with sorafenib resulted in a significant decrease of 111In-bevacizumab uptake in the tumor in the patients with ccRCC (mean change, −60.5%; range, +1.5% to −90.1%). The decrease in uptake was due to destruction of the tumor neovasculature, whereas the VEGF-A expression remained intact. In the patient with papillary RCC, limited uptake without change after sorafenib was observed. Conclusion: RCC lesions were clearly delineated with 111In-bevacizumab scintigraphy. Neoadjuvant treatment with sorafenib resulted in a significant decrease of 111In-bevacizumab uptake in RCC. 111In-bevacizumab scintigraphy can be an attractive biomarker for response and needs further study.
The splenic marginal zone is absent in alymphoplastic aly mutant mice

aly is a unique spontaneous autosomal recessive mutation in mice that causes a deficiency in the systemic lymph nodes (LN) and Peyer's patches (PP). aly also induces abnormal histological findings in the spleen and a deficiency in humoral and cell‐mediated immune functions, although lymphocytes of the aly/aly mouse show virtually normal immune responses in vitro. We studied the structure of the spleen of aly mice in detail by immunohistochemistry and electron microscopy. We found that the spleen of the aly/aly mouse was deficient in the expression of specific antigens for marginal metallophils (MM), marginal zone macrophages (MZM) and fibroblastic reticular cells (FRC), which are components of the marginal zone (MZ) of the spleen. Morphological analysis indicated that the aly/aly spleen is deficient in the structure of MZ, which may, in part, account for the severe immunodeficiency in the aly/aly mouse. We then performed reciprocal bone marrow transplantation experiments (BMT) between normal and aly mice and found a clear correlation between the formation of LN and the development of the splenic MZ in these mice; i.e. successful development of LN was invariably associated with the appearance of the MZ structure, whereas the failure of LN development was always associated with the absence of the development of MZ. These BMT results suggest that a common factor may regulate the generation of both LN and MZ of the spleen.
INTELLIGENT INTERFACE FOR ADJUVANT TREATMENT PLANNING IN BREAST CANCER

The primary course of therapy for breast cancer patients, following surgery, depends on the expected prognosis together with the key clinical indicators. An interface for use by clinical oncologists is proposed, which addresses three fundamental questions, namely; evidence that the currently used Nottingham Prognostic Index can be enhanced by additional clinical features, prognostic inference for individual patients with quantified confidence levels, and visualisation of the patient database by clinical indicator of adjuvant treatment. This interface is underpinned by detailed prognostic analysis validated through longitudinal cohort studies of mortality with 931 TNM stage I/II patients recruited between 1990 and 1993 at Christie Hospital, Wilmslow. The data shown in the interface are Kaplan-Meier curves from prognostic risk groups inferred by cross validation.
Current features of infective endocarditis in elderly patients: results of the International Collaboration on Endocarditis Prospective Cohort Study.

BACKGROUND Elderly patients are emerging as a population at high risk for infective endocarditis (IE). However, adequately sized prospective studies on the features of IE in elderly patients are lacking. METHODS In this multinational, prospective, observational cohort study within the International Collaboration on Endocarditis, 2759 consecutive patients were enrolled from June 15, 2000, to December 1, 2005; 1056 patients with IE 65 years or older were compared with 1703 patients younger than 65 years. Risk factors, predisposing conditions, origin, clinical features, course, and outcome of IE were comprehensively analyzed. RESULTS Elderly patients reported more frequently a hospitalization or an invasive procedure before IE onset. Diabetes mellitus and genitourinary and gastrointestinal cancer were the major predisposing conditions. Blood culture yield was higher among elderly patients with IE. The leading causative organism was Staphylococcus aureus, with a higher rate of methicillin resistance. Streptococcus bovis and enterococci were also significantly more prevalent. The clinical presentation of elderly patients with IE was remarkable for lower rates of embolism, immune-mediated phenomena, or septic complications. At both echocardiography and surgery, fewer vegetations and more abscesses were found, and the gain in the diagnostic yield of transesophageal echocardiography was significantly larger. Significantly fewer elderly patients underwent cardiac surgery (38.9% vs 53.5%; P < .001). Elderly patients with IE showed a higher rate of in-hospital death (24.9% vs 12.8%; P < .001), and age older than 65 years was an independent predictor of mortality. CONCLUSIONS In this large prospective study, increasing age emerges as a major determinant of the clinical characteristics of IE. Lower rates of surgical treatment and high mortality are the most prominent features of elderly patients with IE. Efforts should be made to prevent health care-associated acquisition and improve outcomes in this major subgroup of patients with IE.
Localization of the Transglutaminase Cross-linking Site in SVS III, a Novel Glycoprotein Secreted from Mouse Seminal Vesicle*

The nucleotide sequence ofMpSv-1, a novel androgen-regulated gene exclusively expressed in mouse seminal vesicle, was analyzed to establish a 5′-flanking region of 2123 bp, three exons of 95, 765, and 330 bp, and two introns of 222 and 811 bp. The transcription unit is organized with the first exon encoding a signal peptide, and the second a secreted protein, whereas the third encompasses a 3′-non-translated nucleotide that shares common features of rapid evolving substrates of transglutaminase gene family. The protein sequence deduced from this gene contains 265 amino acid residues in which the central part, residues 116–145, is a region composed of five short tandem repeats, consisting of four amino acid residues, QXK(S/T), whereX is an aliphatic amino acid residue. Among the mouse seminal vesicle secretory proteins that could be resolved by SDS-PAGE into seven major components, SVS I–VII, the antiserum against residues 77–109 of the MpSv-1-translated protein only reacted with SVS III. Matrix-assisted laser desorption/ionization-time of flight mass spectral analysis from a trypsin digest of SVS III supported this protein as derived from MpSv-1. SVS III was immunolocalized to the epithelium of both the primary and secondary folds of the seminal vesicle and the copulatory plug. All of mouse SVS I–III were proven to be substrates of transglutaminase and could be cross-linked readily after the enzyme reaction. The transglutaminase cross-linking site of SVS III was identified to be the tandem repeats of QXK(S/T) in the central part of this protein molecule.
Optimizing Growth Conditions for Digoxin Production in Digitalis lanata Ehrh

Objective: Digoxin is a therapeutic cardenolide widely used to treat various heart conditions such as atrial flutter, atrial fibrillation and heart failure in both Western as well as Chinese medicine. Digoxin is extracted from cultivated Digitalis lanata Ehrh. plants, known as Mao Hua Yang Di Huang in Chinese medicine. This manuscript presents two studies that were conducted to optimize the cultivation conditions for digoxin production in the TCM Mao Hua Yan Di Huang in a greenhouse under GAP conditions. Methods: Two experiments were designed in which 4 growth conditions were compared. Levels of digoxin, gitoxin, digitoxin, α-acetyldigoxin, β-acetyl-digoxin were measured using HPLC-UV and compared between the conditions. Results: Normal soil, no CO2 enrichment combined with a cold shock was found to be the optimal condition for producing digoxin in the first experiment. Gitoxin content was significantly lower in plants grown in this condition. Mechanical stress as well as the time of harvesting showed no statistically significant differences in the production of cardenolides. In the second experiment the optimal condition was found to be a combination of cold nights, sun screen, fertilizer use and no milled soil. Conclusion: This study shows that digoxin production can be increased by controlling the growth conditions of D. lanata Ehrh. The effect of cold was important in both experiments for improving digoxin production. Cultivating Chinese herbal medicines in optimized greenhouse conditions might be an economically attractive alternative to regular open air cultivation.
GPR126 Protein Regulates Developmental and Pathological Angiogenesis through Modulation of VEGFR2 Receptor Signaling*

Background: GPR126 plays critical roles in development, but its function in vessels is not well characterized. Results: GPR126 regulates angiogenesis by modulating endothelial cell proliferation and migration via regulation of Vegfr2 expression. Conclusion: GPR126 is important for physiological and pathological angiogenesis. Significance: This finding provides a new functional mechanism for the regulation of angiogenesis. Angiogenesis, the formation of new blood vessels from pre-existing ones, is essential for development, wound healing, and tumor progression. The VEGF pathway plays irreplaceable roles during angiogenesis, but how other signals cross-talk with and modulate VEGF cascades is not clearly elucidated. Here, we identified that Gpr126, an endothelial cell-enriched gene, plays an important role in angiogenesis by regulating endothelial cell proliferation, migration, and tube formation. Knockdown of Gpr126 in the mouse retina resulted in the inhibition of hypoxia-induced angiogenesis. Interference of Gpr126 expression in zebrafish embryos led to defects in intersegmental vessel formation. Finally, we identified that GPR126 regulated the expression of VEGFR2 by targeting STAT5 and GATA2 through the cAMP-PKA-cAMP-response element-binding protein signaling pathway during angiogenesis. Our findings illustrate that GPR126 modulates both physiological and pathological angiogenesis through VEGF signaling, providing a potential target for the treatment of angiogenesis-related diseases.
Apomorphine blocks form-deprivation myopia in chickens by a dopamine D2-receptor mechanism acting in retina or pigmented epithelium

Abstract Studies of form-deprivation myopia (FDM) in animal models have shown that postnatal ocular growth is regulated by the quality of patterned images on the retina. One of the major challenges in myopia research is to identify the biochemical mechanisms which translate retinal visual responses into signals that regulate scleral growth. Dopamine (DA) has been implicated in this process, since retinal DA levels decline in FDM and subconjunctival injections of apomorphine (Apo, a nonspecific DA agonist) prevent FDM in a dose-dependent way (Stone et al., 1989). To gain insight into where and how DA ligands act to regulate ocular elongation, we compared the action and distribution of DA receptor ligands injected intravitreally vs. subconjunctivally in young chicks. Ocular length was measured by A-scan ultrasound. We found that daily intravitreal injections of Apo block FDM at a 50% effective dose (ED50) of 5 pg per day, or a peak concentration in the vitreous humor of 108 pM, compared to an ED50 of 2.5 ng for subconjunctival injections as reported by Stone et al. (1989, 1990). [3H]-spiperone, a D2-receptor antagonist, reached average maximum retinal concentrations of 160 pM and 260 pM, during the first hour after intravitreal and subconjunctival administration, respectively, at the ED50 dose. In contrast, the maximum spiperone concentrations in the retinal pigment epithelium (RPE) were 30 pM and 410 pM, respectively, after intravitreal or subconjunctival ED50 doses. Spiperone concentrations in sclera after ED50 doses to the two sites differed by 4 x 104 (0.4 pM vs. 1.7 nM, respectively). The FDM-preventing action of Apo was blocked completely by simultaneous administration of spiperone but not by SCH 23390 (a D1-receptor antagonist) in 100-fold molar excess. These results show that apomorphine acts to prevent FDM at an intraocular site, presumably in retina and/or pigment epithelium, but not sclera, whether administered intravitreally or subconjunctivally. A dose yielding a concentration of 100–260 pM, delivered ≤1 h per day, produces half-maximal inhibition. This action is mediated by D2-receptors, for which the dissociation constant for apomorphine is ≤1 nM. The retinal pigment epithelium may act as a trophic relay station, responding to a retinal messenger which may be DA and secreting scleral growth-regulator(s) from its basal surface.
Relationship of serum antibody to risk of respiratory syncytial virus infection in elderly adults.

The relationship of serum antibody to respiratory syncytial virus (RSV) and risk of RSV infection was prospectively evaluated in frail elderly persons. Baseline blood samples from 22 subjects who developed symptomatic RSV infection during the 26-month study and from 22 control subjects who did not become infected with RSV were compared. The mean serum IgG titer to RSV fusion protein was significantly lower in the RSV-infected group than in the controls (15.4 +/- 1.6 vs. 16.4 +/- 1.8, P = .05), as were the neutralizing titers to group A RSV (12.4 +/- 2.2 vs. 14.2 +/- 2.2, P = .008) and group B virus (9.1 +/- 2.1, vs. 10.3 +/- 1.5, P = .01). These results suggest that older adults with low titers of serum neutralizing antibody may be at greater risk of developing symptomatic RSV infection than those who have high antibody titers.
A Survey on Skin Cancer Detection System

Skin cancers are the most common form of cancers found in humans. This is the most deadly form of cancer. Most of the skin cancers are curable at initial stages. So an early detection of skin cancer can save the patients. With the advancement of technology, early detection of skin cancer is possible. According to the literature, skin lesion structure is an important diagnostic parameter. In this paper, an introduction is given about different characteristics of the skin cancer and a brief review has been on types of skin cancer, skin cancer causes & symptoms. A survey has been given which carry out the analysis of skin cancer detection by different methods of the diagnosing methodology uses Image processing techniques. Finally, general method of skin cancer detection is presented with all possible image segmentation algorithms.
Tyk2 Negatively Regulates Adaptive Th1 Immunity by Mediating IL-10 Signaling and Promoting IFN-γ-Dependent IL-10 Reactivation1

The Jak, Tyk2, is activated in response to IL-12 and IFN-αβ and promotes IFN-γ production by Th1-type CD4 cells. Mice deficient in Tyk2 function have been previously shown to be resistant to autoimmune arthritis and septic shock but are acutely susceptible to opportunistic pathogens such as Toxoplasma gondii. In this study, we show that Tyk2, in addition to mediating the biological effects of IL-12 and IFN-αβ, is an important regulator for the signaling and expression of the immunosuppressive cytokine IL-10. In the absence of Tyk2, Ag-reactive CD4 cells exhibit impaired IL-10 synthesis following rechallenge of T. gondii vaccine-primed mice. The impaired IL-10 reactivation leads to unopposed antimicrobial effector mechanisms which results in a paradoxically superior protection of immune Tyk2−/− mice against virulent T. gondii challenge. We further demonstrate that Tyk2 indirectly controls CD4 IL-10 reactivation by signaling for maximal IFN-γ secretion. The unexpected role of IFN-γ in mediating IL-10 reactivation by Th1 cells provides compelling evidence that conditions driving Th1 responses establish a negative feedback loop, which will ultimately lead to its autoregulation. Thus, Tyk2 can be viewed as a dual-function Jak, mediating both pro and anti-inflammatory cytokine responses.
An Overview of Feature Extraction Methods in CBIR

In multimedia processing, content based image retrieval plays the important role. This paper presents an overview of the feature extraction methods related to the CBIR. Image segmentation is first key step to have the features of particular image. Image can be indexed by these features in terms of the vectors. Here, we have studied the past and present methods of feature extraction. Retrieval time can be saved by using the efficient feature extraction method. Paper ends with the importance of segmentation and retrieval time. This paper may help the CBIR researchers for identifying or developing the feature extraction strategy or technique.
Reduction of ischemic injury by nitroglycerin during acute myocardial infarction.

ARRHYTHMIAS and cardiac failure are two of the major, potentially lethal sequelae of acute myocardial infarction. Although measures used to treat arrhythmias are usually considered separately from those used to treat myocardial failure, it is clear that arrhythmias and myocardial failure share a common precipitating mechanism —severe ischemic injury (as defined by a reduction in oxygen delivery to the myocardial cell resulting initially in aberrations of biochemical, electrophysiologic and mechanical function and, if unrelieved, ultimately in cell death). Moreover, in some cases of acute myocardial infarction complicated by left ventricular failure and ventricular arrhythmias, the temporal sequence of events suggests .
A Non-Isolated Single Phase On-Line UPS with Universal Input Output Voltage

This work deals with the development of a single phase on-line uninterruptible power supply(UPS) with universal input output voltage rating(110V/220V). The converter is consisted of an ac-dc/dc-dc three level boost converter combined with a double half bridge inverter. In this type of configuration, size, cost and efficiency are improved due to the fact of reduced number of switches, batteries and not requiring isolation transformer operating in lower frequency to realize bypass operation. A higher frequency operation of both converters is adopted using a passive non-dissipative snubber circuit in the boost converter and latest available commercial technology of IGBTs switches in inverters. A simple and well known control strategy is presented. Principle of operation, simulated results and experimental results of a 2.6kVA prototype is also presented to demonstrate UPS performance.