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Objective: This study aims to identify the incidence of malignancy in solitary nodule thyroid in a tertiary care hospital in Kalaburagi, Karnataka. Methods: This was a prospective non-randomized hospital-based interventional study carried out on 50 patients over a period of 1 y, who presented with clinically palpable solitary thyroid swellings and subsequently underwent surgery for the same at the Department of General surgery, Gulbarga Institute of Medical Sciences, Kalaburagi, Karnataka. Results: Over the total duration of the study period, there were 50 cases of clinically detected solitary thyroid nodule with a high female preponderance. The mean age of the incidence of solitary thyroid nodule was 40.6 y. The incidence of malignancy in solitary thyroid nodule was found to be 18%. Conclusion: It is concluded from the present study that 18% of solitary thyroid nodules are malignant, with female preponderance and a mean age of solitary thyroid nodule is 40.62 y.

Some strongly nonlinear oscillators have been investigated with the help of combined modified Lindstedt–Poincare and homotopy perturbation methods. The solutions are more accurate than those obtained by the modified Lindstedt–Poincare method. Moreover, the determination of solutions is simpler than usual homotopy perturbation methods. Some similarities and dissimilarities between the present method and other existing methods have also been discussed.

BackgroundRisk factors for COPD in high-income settings are well understood; however, less attention has been paid to contributors of COPD in low-income and middle-income countries (LMICs) such as pulmonary tuberculosis. We sought to study the association between previous tuberculosis disease and COPD by using pooled population-based cross-sectional data in 13 geographically diverse, low-resource settings.MethodsWe pooled six cohorts in 13 different LMIC settings, 6 countries and 3 continents to study the relationship between self-reported previous tuberculosis disease and lung function outcomes including COPD (defined as a postbronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) below the lower limit of normal). Multivariable regressions with random effects were used to examine the association between previous tuberculosis disease and lung function outcomes.ResultsWe analysed data for 12 396 participants (median age 54.0 years, 51.5% male); 332 (2.7%) of the participants had previous tuberculosis disease. Overall prevalence of COPD was 8.8% (range 1.7%–15.5% across sites). COPD was four times more common among those with previous tuberculosis disease (25.7% vs 8.3% without previous tuberculosis disease, p1(−0.70, 95% CI −0.84 to −0.55), FVC (−0.44, 95% CI −0.59 to −0.29) and the FEV1:FVC ratio (−0.63, 95% CI −0.76 to −0.51) when compared with those without previous tuberculosis disease.ConclusionsPrevious tuberculosis disease is a significant and under-recognised risk factor for COPD and poor lung function in LMICs. Better tuberculosis control will also likely reduce the global burden of COPD.

The effect of mechanical exclusion devices and its number in combination viz. probe trap (A; 1-3), two-in-one trap with 3 mm perforations (B; 1-5) and two-in-one trap with 2 mm perforations (C; 1-3) were investigated to test the efficiency of these traps for trapping larvae and adults of khapra beetle Trogoderma granarium Everts. Colour change and weight loss (%) happening in wheat stored in bins of 50 kg capacity for six months were used as the criteria. The experiments were planned using a three-factor-three-level Box and Behnken design of response surface methodology and were optimized for maximum trapping, with minimum change in colour and weight loss. Analysis of variance (ANOVA) revealed significantly (p

Allogeneic hematopoietic cell transplantation (HCT) is a well-established and potentially curative treatment for a broad range of hematological diseases, bone marrow failure states, and genetic disorders. Acute graft-versus-host disease (GvHD), mediated by donor T cells attacking host tissues, still represents a major cause of morbidity and mortality following allogeneic HCT. Current approaches to diagnosis of gastrointestinal acute GvHD rely on clinical and pathological criteria that manifest at late stages of disease. New strategies allowing for GvHD prediction and diagnosis, prior to symptom onset, are urgently needed. Noninvasive antibody-based positron emission tomography (PET) (immunoPET) imaging of T-cell activation post–allogeneic HCT is a promising strategy toward this goal. In this work, we identified inducible T-cell costimulator (ICOS) as a potential immunoPET target for imaging activated T cells during GvHD. We demonstrate that the use of the Zirconium-89-deferoxamine-ICOS monoclonal antibody PET tracer allows in vivo visualization of donor T-cell activation in target tissues, namely the intestinal tract, in a murine model of acute GvHD. Importantly, we demonstrate that the Zirconium-89-deferoxamine-ICOS monoclonal antibody PET tracer does not affect GvHD pathogenesis or the graft-versus-tumor (GvT) effect of the transplant procedure. Our data identify ICOS immunoPET as a promising strategy for early GvHD diagnosis prior to the appearance of clinical symptoms.

Human bone marrow stromal cell (hBMSC)–derived exosomes are promising therapeutics for inflammatory diseases due to their unique microRNA (miRNA) and protein cargos. Periodontal diseases often present with chronicity and corresponding exuberant inflammation, which leads to loss of tooth support. In this study, we explored whether hBMSC exosomes can affect periodontitis progression. hBMSC exosomes were isolated from cell culture medium through sequential ultracentrifugation. miRNAs and proteins that were enriched in hBMSC exosomes were characterized by RNA sequencing and protein array, respectively. hBMSC exosomes significantly suppressed periodontal keystone pathogen Porphyromonas gingivalis–triggered inflammatory response in macrophages in vitro. Transcriptomic analysis suggested that exosomes exerted their effects through regulating cell metabolism, differentiation, and inflammation resolution. In vivo, weekly exosome injection into the gingival tissues reduced the tissue destruction and immune cell infiltration in rat ligature-induced periodontitis model. Collectively, these findings suggest that hBMSC-derived exosomes can potentially be used as a host modulation agent in the management of periodontitis.

Onion slices were dried in a low-humidity air-assisted hybrid solar dryer. Drying occurred in the falling rate period, and the drying rate was attenuated with the initial moisture content of the samples. The effects of different drying air temperatures (50, 60, 70°C) and KMS pre-treatments (0.1, 0.3, 0.5%) on drying characteristics of onion slices were also studied. Eight thin layer drying mathematical models viz. Newton, Page, Modified Page, Exponential, Asymptotic, Logistic, Wang and Singh, and two-term exponential were investigated and the results were compared to their goodness of fit in terms of coefficient of correlation (r), standard error (es), and the mean square of the deviation χ2. Drying characteristics of onion slices were better delineated by Page’s regression model for hybrid solar drying with values for the coefficient of correlation (0.9962–0.9999), standard error (0.0048–0.0431), and χ² (5.98E-05 to 2.16E-03). Effective moisture diffusivity values of onion slices ranged between 1.33E-08 m2.s-1 to 2.49E-08 m2.s-1 for the drying conditions under investigation.

The aloe vera pulp contains more than 98% water and less than 1% total soluble solids (TSS). Blending of pineapple juice and roselle extract with aloe vera may not only increases the TSS level but also add other nutritional properties in the final mixed products. The current study was carried out to investigate the different formulations and the quality of various types of mixed beverages prepared from aloe vera, roselle herb and pineapple juice. Developed products were evaluated for their chemical properties as well as sensory attributes. In addition, selected products were tested for shelf-life potentials. Formulated drinks and juices were found as highly nutritious (maximum of 6.86 mg/100 ml ascorbic acid, 0.045% Ca, 0.26% Mg, 0.154% K, 0.034%Na, and 12.09 ppm Fe). Sensory evaluation revealed that products with 20% and 40% aloe vera pulp with pineapple and roselle extract were highly liked by the consumers. With the storage time, pH and ascorbic acid content decreased (maximum around 40% for pH and around 10% for ascorbic acid respectively) in all the formulated beverages, while TSS increased regardless of the formulations. In addition, aloe vera with pineapple and sugar blend exhibited an acceptable level of microbial load during the shelf-life study. Results from this study suggest that it could be possible to commercially produce aloe vera based value added products, which in turn could play an important role in addressing socioeconomic as well as health conditions. Ann. Bangladesh Agric. (2021) 25 (1) : 43-54

The pulse beetle Callosobruchus chinensis (L.) is a major pest of stored chickpea. In the present study, efficacy of neem (0.5 and 1.0%) and turmeric powders (0.5 and 1.0%) has been evaluated against this pest, in combination with mustard oil (0.3%), thermal treatment @ 60oC for 20 min and packing materials including open, PP (polypropylene) and LD (low density polyethylene). The results revealed increased efficacy with concentration of neem and turmeric powder. Use of neem oil @ 1.0%+ mustard oil @ 0.3% kept in open packing, proved to be significantly superior at four months of storage. Turmeric powder @ 0.5%+ mustard oil @ 0.3% treated grains showed a significantly better germination. Moisture content differed significantly with treated samples. The colour change and myroflora incidence were comparatively minimum with neem leaf powder @ 0.5%+ mustard oil @ 0.3% treated samples. Thermal treated grains proved superior compared to botanicals, whereas, colour change led to significantly lesser effect. Among the packings, PP and LD packed samples significantly influenced the infestation and germination irrespective of the botanicals.

Ready to eat, nutritious and low-cost snack was developed by composite flour containing defatted soya, rice, salt, radish leaves and pea pods powder. The best possible combination of process parameter was obtained with response surface methodology (RSM) using Box Behnken design. The different process variables viz., screw speed, die temperature, feed moisture and composition of base and supplement materials were optimized to obtain good quality soybean-rice based snack food. The designed experimental runs were conducted to obtain the optimal conditions as 360.42 rpm speed of screw (SS), 152.29°C die temperature (DT), 13.17% feed moisture (FM), 35% vegetable waste-soy powder (VW-SP) proportion and 65% of base flour. The results revealed that the addition of vegetable waste (radish leaves and pea pods powder) and soy powder had the most significant impact on all process variables followed by the feed moisture content. The blend proportion under optimum extrusion conditions had improved the nutritional quality of snack food with 1.55g/ 100g of fiber and 20.61g/100g of protein content and overall acceptability of 78.41%.

Figure S1 shows Surface B7H3 CAR, PD-1, and LAG-3 expression of T-cells transduced with CAR retroviral supernatant

PKM2 analysis in TP459 neurospheres

Supplementary Figure 1 shows [18F]F-AraG Structure and Schematic of AraG Uptake into T Cells Supplementary Figure 2 shows [18F]F-AraG and [3H]F-AraC Uptake and Retention Across Various Immune Cell Lines Supplementary Figure 3 shows AraG Competitive Inhibition of [18F]F-AraG Uptake Across Various Immune Cell Lines Supplementary Figure 4 shows Comparison of [18F]F-AraG and [3H]F-AraC Uptake and Retention Across Various Solid Tumor Cell Lines Supplementary Figure 5 shows Western Blot Analysis of dCK Expression in Wild-type and Mutant CCRF-CEM cells Supplementary Figure 6 shows dGK overexpression in CHO-K1 cells leads to increased [18F]F-AraG uptake and retention Supplementary Figure 7 shows [3H]F-AraC Accumulates in Cells via dCK Activity Supplementary Figure 8 shows Uptake of [18F]F-AraG in Activated Versus Resting Murine T Cells Supplementary Figure 9 shows Isolation and Activation of Primary Human T Cells Supplementary Figure 10 shows Uptake and Retention of [3H]AraG and [3H]F-AraC in Resting and Activated Human Primary T Cells Supplementary Figure 11 shows Evaluation of GFP+ Donor T cells in Spleens and Cervical Lymph Nodes (CLNs) at Day 3 and Day 10 of Acute GVHD Supplementary Figure 12 shows Evaluation of Proliferation of Donor T Cells in Cervical Lymph Nodes

Clinical Characteristics of patients imaged with [18F]DASA-23

Figure S2 shows characterization of B7H3-sr39tk CAR phenotypic subsets

[18F]DASA-23 administered activity in brain tumor patients

A major barrier to successful use of allogeneic hematopoietic cell transplantation is acute graft-versus-host disease (aGVHD), a devastating condition that arises when donor T cells attack host tissues. With current technologies, aGVHD diagnosis is typically made after end-organ injury and often requires invasive tests and tissue biopsies. This affects patient prognosis as treatments are dramatically less effective at late disease stages. Here, we show that a novel PET radiotracer, 2′-deoxy-2′-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG), targeted toward two salvage kinase pathways preferentially accumulates in activated primary T cells. [18F]F-AraG PET imaging of a murine aGVHD model enabled visualization of secondary lymphoid organs harboring activated donor T cells prior to clinical symptoms. Tracer biodistribution in healthy humans showed favorable kinetics. This new PET strategy has great potential for early aGVHD diagnosis, enabling timely treatments and improved patient outcomes. [18F]F-AraG may be useful for imaging activated T cells in various biomedical applications. Cancer Res; 77(11); 2893–902. ©2017 AACR.

Imaging of IC-2

Day4_Control

Purpose:Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and patients with GBM.Experimental Design:[18F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/μmol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next, we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with glioma.Results:In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio of 3.6 ± 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood–brain barrier and was rapidly cleared. In patients with GBM, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced MRI. The uptake of [18F]DASA-23 was markedly elevated in GBMs compared with normal brain, and it identified a metabolic nonresponder within 1 week of treatment initiation.Conclusions:We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy–induced normalization of aberrant cancer metabolism.

Day7_Control

Hematology laboratory testing results of patients imaged with [18F]DASA-23

Imaging of IC-4

Imaging strategies to monitor chimeric antigen receptor (CAR) T-cell biodistribution and proliferation harbor the potential to facilitate clinical translation for the treatment of both liquid and solid tumors. In addition, the potential adverse effects of CAR T cells highlight the need for mechanisms to modulate CAR T-cell activity. The herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene has previously been translated as a PET reporter gene for imaging of T-cell trafficking in patients with brain tumor. The HSV1-TK enzyme can act as a suicide gene of transduced cells through treatment with the prodrug ganciclovir. Here we report the molecular engineering, imaging, and ganciclovir-mediated destruction of B7H3 CAR T cells incorporating a mutated version of the HSV1-tk gene (sr39tk) with improved enzymatic activity for ganciclovir. The sr39tk gene did not affect B7H3 CAR T-cell functionality and in vitro and in vivo studies in osteosarcoma models showed no significant effect on B7H3 CAR T-cell antitumor activity. PET/CT imaging with 9-(4-[18F]-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]FHBG) of B7H3-sr39tk CAR T cells in an orthotopic model of osteosarcoma revealed tumor homing and systemic immune expansion. Bioluminescence and PET imaging of B7H3-sr39tk CAR T cells confirmed complete tumor ablation with intraperitoneal ganciclovir administration. This imaging and suicide ablation system can provide insight into CAR T-cell migration and proliferation during clinical trials while serving as a suicide switch to limit potential toxicities.Significance:This study showcases the only genetically engineered system capable of serving the dual role both as an effective PET imaging reporter and as a suicide switch for CAR T cells.

[18F]DASA-23 Radiosynthesis

Evaluation of PKM2 expression in U87-GFP/luc orthotopic GBM

Vital signs of the patients administered with [18F]DASA-23

FIgure S3 shows B7H3 CAR expression of remaining viable B7H3-sr39tk CAR T-cells after GCV treatment

Day4_GVHD

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Figure S5 shows flow cytometry of spleens at 9 days following the final GCV treatment

Comparative metabolic PET/CT imaging in U87-GFP/luc GBM mice

CHO Cell Transfection Tracer Uptake and Efflux Assays for Adherent Cells Western Blot Immunofluorescence Staining of Lymphoid Organs Ex Vivo Donor T Cell Proliferation Analysis Automated preparation of [18F]FAraG for human imaging using the Neptis perform PET synthesizer Imaging Studies in Humans Statistics