RESUMO
Multiple myeloma (MM) is a clonal plasma cell malignancy typically associated with the high and uniform expression of the CD38 transmembrane glycoprotein. Daratumumab is a humanized IgG1κ CD38 monoclonal antibody (MoAb) which has demonstrated impressive single agent activity even in relapsed refractory MM patients as well as strong synergy with other anti-MM drugs. Natural Killer (NK) cells are cytotoxic immune effector cells that mediate in vivo tumour immunosurveillance. NK cells also play an important role during MoAb therapy by inducing antibody dependent cellular cytotoxicity (ADCC) via their FcγRIII (CD16) receptor. Furthermore, 15% of the population express a naturally occurring variant of CD16 harbouring a single-point polymorphism (F158V). However, the contribution of NK cells to the efficacy of daratumumab remains debatable as clinical data clearly indicate the rapid depletion of CD38high peripheral blood NK cells in patients upon daratumumab administration. In contrast, CD38low peripheral blood NK cells have been shown to survive daratumumab mediated fratricide in vivo, while still retaining their potent anti-MM cytolytic effector functions ex vivo. Therefore, we hypothesize that transiently expressing the CD16F158V receptor using a "safe" mRNA electroporation-based approach on CD38low NK cells in combination with daratumumab could represent a novel therapeutic option for treatment of MM. In the present study, we investigate a NK cell line (KHYG-1), derived from a patient with aggressive NK cell leukemia, as a platform for generating CD38low NK cells expressing CD16F158V which can be administered as an "off-the-shelf" therapy to target both CD38high and CD38low tumour clones in patients receiving daratumumab.
Assuntos
ADP-Ribosil Ciclase 1/metabolismo , Anticorpos Monoclonais/uso terapêutico , Células Matadoras Naturais/imunologia , Mieloma Múltiplo/tratamento farmacológico , Receptores de IgG/metabolismo , Animais , Anticorpos Monoclonais/farmacologia , Linhagem Celular Tumoral , Humanos , Camundongos , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologiaRESUMO
[This corrects the article DOI: 10.3389/fpls.2023.1282217.].
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Aims: To measure and compare length, width and luminal diameters of semi-circular canals (SCC) on Multiplanar reformatted CT images in individuals without any features of vestibular dysfunction. Materials And Methods: A prospective, cross sectional, observational study was conducted in a tertiary care hospital in October - November 2021. Multiplanar reformatted CT temporal bone images of 50 participants without features of vestibular dysfunction were used to measure the curved lengths, widths and luminal diameters of the three semi-circular canals. Unpaired t-test was used to ascertain and compare the values obtained. Results: Fifty participants, 27 women and 23 men (mean age 38.5 years) were included in the study. Mean curved lengths of Superior, posterior and Lateral SCCs were 1.37 cm, 1.33 cm and 1.19 cm respectively. Semi-circular width of Superior SCC (4.8 mm) was significantly larger than Posterior SCC (4.17 mm, p = 0.03) which was significantly larger than Lateral SCC (3.65 mm, p = 0.04). No significant difference was found between mean mid luminal diameters of the three SCCs. Mid luminal diameters were significantly smaller than the diameters at either ends of all SCCs. Conclusion: The results can potentially serve as reference values for Indians and for further studies on pathophysiology of disequilibrium.
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Sensor-based decision tools provide a quick assessment of nutritional and physiological health status of crop, thereby enhancing the crop productivity. Therefore, a 2-year field study was undertaken with precision nutrient and irrigation management under system of crop intensification (SCI) to understand the applicability of sensor-based decision tools in improving the physiological performance, water productivity, and seed yield of soybean crop. The experiment consisted of three irrigation regimes [I1: standard flood irrigation at 50% depletion of available soil moisture (DASM) (FI), I2: sprinkler irrigation at 80% ETC (crop evapo-transpiration) (Spr 80% ETC), and I3: sprinkler irrigation at 60% ETC (Spr 60% ETC)] assigned in main plots, with five precision nutrient management (PNM) practices{PNM1-[SCI protocol], PNM2-[RDF, recommended dose of fertilizer: basal dose incorporated (50% N, full dose of P and K)], PNM3-[RDF: basal dose point placement (BDP) (50% N, full dose of P and K)], PNM4-[75% RDF: BDP (50% N, full dose of P and K)] and PNM5-[50% RDF: BDP (50% N, full P and K)]} assigned in sub-plots using a split-plot design with three replications. The remaining 50% N was top-dressed through SPAD assistance for all the PNM practices. Results showed that the adoption of Spr 80% ETC resulted in an increment of 25.6%, 17.6%, 35.4%, and 17.5% in net-photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), and intercellular CO2 concentration (Ci), respectively, over FI. Among PNM plots, adoption of PNM3 resulted in a significant (p=0.05) improvement in photosynthetic characters like Pn (15.69 µ mol CO2 m-2 s-1), Tr (7.03 m mol H2O m-2 s-1), Gs (0.175 µmol CO2 mol-1 year-1), and Ci (271.7 mol H2O m2 s-1). Enhancement in SPAD (27% and 30%) and normalized difference vegetation index (NDVI) (42% and 52%) values were observed with nitrogen (N) top dressing through SPAD-guided nutrient management, helped enhance crop growth indices, coupled with better dry matter partitioning and interception of sunlight. Canopy temperature depression (CTD) in soybean reduced by 3.09-4.66°C due to adoption of sprinkler irrigation. Likewise, Spr 60% ETc recorded highest irrigation water productivity (1.08 kg ha-1 m-3). However, economic water productivity (27.5 INR ha-1 m-3) and water-use efficiency (7.6 kg ha-1 mm-1 day-1) of soybean got enhanced under Spr 80% ETc over conventional cultivation. Multiple correlation and PCA showed a positive correlation between physiological, growth, and yield parameters of soybean. Concurrently, the adoption of Spr 80% ETC with PNM3 recorded significantly higher grain yield (2.63 t ha-1) and biological yield (8.37 t ha-1) over other combinations. Thus, the performance of SCI protocols under sprinkler irrigation was found to be superior over conventional practices. Hence, integrating SCI with sensor-based precision nutrient and irrigation management could be a viable option for enhancing the crop productivity and enhance the resource-use efficiency in soybean under similar agro-ecological regions.
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Photosynthesis, crop health and dry matter partitioning are among the most important factors influencing crop productivity and quality. Identifying variation in these parameters may help discover the plausible causes for crop productivity differences under various management practices and cropping systems. Thus, a 2-year (2019-2020) study was undertaken to investigate how far the integrated crop management (ICM) modules and cropping systems affect maize physiology, photosynthetic characteristics, crop vigour and productivity in a holistic manner. The treatments included nine main-plot ICM treatments [ICM1 to ICM4 - conventional tillage (CT)-based; ICM5 to ICM8 - conservation agriculture (CA)-based; ICM9 - organic agriculture (OA)-based] and two cropping systems, viz., maize-wheat and maize + blackgram-wheat in subplots. The CA-based ICM module, ICM7 resulted in significant (p < 0.05) improvements in the physiological parameters, viz., photosynthetic rate (42.56 µ mol CO2 m-2 sec-1), transpiration rate (9.88 m mol H2O m-2 sec-1) and net assimilation rate (NAR) (2.81 mg cm-2 day-1), crop vigour [NDVI (0.78), chlorophyll content (53.0)], dry matter partitioning toward grain and finally increased maize crop productivity (6.66 t ha-1) by 13.4-14.2 and 27.3-28.0% over CT- and OA-based modules. For maize equivalent grain yield (MEGY), the ICM modules followed the trend as ICM7 > ICM8 > ICM5 > ICM6 > ICM3 > ICM4 > ICM1 > ICM2 > ICM9. Multivariate and PCA analyses also revealed a positive correlation between physiological parameters, barring NAR and both grain and stover yields. Our study proposes an explanation for improved productivity of blackgram-intercropped maize under CA-based ICM management through significant improvements in physiological and photosynthetic characteristics and crop vigour. Overall, the CA-based ICM module ICM7 coupled with the maize + blackgram intercropping system could be suggested for wider adoption to enhance the maize production in semiarid regions of India and similar agroecologies across the globe.
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The plantaris muscle (PM) is a vestigial muscle in human. The PM arises as a small muscular belly from the lateral condyle of the femur and then its long tendon inserts into the calcaneum or blends with the tendocalcaneus. There are many reports to describe the variations in the origin, nature of muscle, course of the tendon, and insertion of PM. However, here we report a case of a rare and unreported variation of PM with one common origin and two muscle bellies with peculiar relations with the neurovascular bundle in the popliteal fossa. Although its anatomical functions are insignificant, its tendon is useful as a graft in various reconstructive surgeries and variation in this muscle and its relation to nearby neurovascular bundle may be of clinical interest. Therefore, the present variation is worth considering in predicting uncommon neurovascular entrapment in the leg and may also be useful in various surgical procedures in the region of the knee joint.