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Gastrointestinal stromal tumors (GIST) are the most common type of soft tissue sarcoma that occur throughout the gastrointestinal tract. Most of these tumors are caused by oncogenic activating mutations in the KIT or PDGFRA genes. The NCCN Guidelines for GIST provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with these tumors. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised systemic therapy options for unresectable, progressive, or metastatic GIST based on mutational status, and updated recommendations for the management of GIST that develop resistance to specific tyrosine kinase inhibitors.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Aggressive Mature B-Cell Lymphomas include recommendations for the diagnosis and management of pediatric patients with primary mediastinal large B-cell lymphoma (PMBL) and sporadic variants of Burkitt lymphoma and diffuse large B-cell lymphoma. PMBL is now considered as a distinct entity arising from mature thymic B-cells accounting for 2% of mature B-cell lymphomas in children and adolescents. This discussion section includes the recommendations outlined in the NCCN Guidelines for the diagnosis and management of pediatric patients with PMBL.

Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.

The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved in recent years. Targeted therapy with Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors has emerged as an effective chemotherapy-free option for patients with previously untreated or relapsed/refractory CLL/SLL. Undetectable minimal residual disease after the end of treatment is emerging as an important predictor of progression-free and overall survival for patients treated with fixed-duration BCL-2 inhibitor-based treatment. These NCCN Guidelines Insights discuss the updates to the NCCN Guidelines for CLL/SLL specific to the use of chemotherapy-free treatment options for patients with treatment-naïve and relapsed/refractory disease.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte–predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase–positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase–negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.

All else equal, parasites that harm host fitness should depress densities of their hosts. However, parasites that alter host traits may increase host density via indirect ecological interactions. Here, we show how depression of foraging rate of infected hosts can produce such a hydra effect. Using a foraging assay, we quantified reduced foraging rates of a zooplankton host infected with a virulent fungal parasite. We then parameterized a dynamical model of hosts, parasites, and resources with this foraging function, showing how foraging depression can create a hydra effect. Mathematically, the hydra arose when increased resource productivity exceeded any increase in resource consumption per host. Therefore, the foraging-mediated hydra effect more likely emerged (1) for hosts that strongly control logistic-like resources and (2) during larger epidemics of moderately virulent parasites. We then analyzed epidemics from 13 fungal epidemics in nature. We found evidence for a foraging-mediated hydra effect: large outbreaks depressed foraging rate and correlated with increased densities of both algal resources and

In the last decade, a better understanding of the molecular pathogenesis of B-cell non-Hodgkin lymphomas has resulted in the development of novel targeted therapies, such as small molecule inhibitors of select kinases in the B-cell receptor pathway, antibody–drug conjugates, and small molecules that target a variety of proteins (eg, CD-19, EZH2, and XPO-1–mediated nuclear export). Anti-CD19 CAR T-cell therapy, first approved for relapsed/refractory (R/R) diffuse large B-cell lymphoma, has also emerged as a novel treatment option for R/R follicular lymphoma and mantle cell lymphoma. These NCCN Guideline Insights highlight the new targeted therapy options included in the NCCN Guidelines for B-Cell Lymphomas for the treatment of R/R disease.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Herein, we report for the first time a transition-metal-free frustrated Lewis pair (FLP) catalyzed CHF

BACKGROUND Hypertension is a silent killer, an asymptomatic chronic disorder if left untreated which results in major health problems. Goal of treatment is to decrease the morbidity and mortality associated with cardiovascular and cerebrovascular complications of hypertension when it is associated with dyslipidaemia. The renin angiotensin system plays an important role in the regulation of blood pressure and in the pathogenesis of hypertension. Telmisartan is an ARB (angiotensin receptor blocker) and Enalapril is an ACE inhibitor. The purpose of this study is to compare the efficacy of Telmisartan with Enalapril in patients of essential hypertension with dyslipidaemia, and to observe the effects of Telmisartan and Enalapril on blood lipid levels of these patients. METHODS This is a prospective, randomized, comparative and open label study conducted among 70 patients who were included in the study and were divided in to two groups. Group A - consisting of 35 patients receiving Telmisartan 40 mg, and Group B receiving Enalapril 5 mg orally once a day. Informed consent was obtained from all the patients. Follow up was done after 4, 8 and 12 weeks. Blood pressure was recorded at every visit and lipid profile was done at the time of enrolment and after 12 weeks of study period. RESULTS Baseline demographic attributes were comparable between both the groups including total cholesterol and low-density lipoprotein (LDL). The mean reduction in systolic and diastolic blood pressure (BP) after 12 weeks was highly significant (P value < 0.001) in both the groups but when mean reduction in SBP & DBP was compared, there was no significant difference (P > 0.05) between the drugs. Blood levels of total cholesterol, LDL, triglyceride had significantly reduced (P < 0.05) in Telmisartan group compared to Enalapril group after 12 weeks of follow up and mean high density lipoprotein (HDL) level significantly increased in Telmisartan group (P < 0.05) but no increment was seen in Enalapril group. CONCLUSIONS Telmisartan and Enalapril had comparable antihypertensive effect and significant reduction in blood pressure was seen after 12 weeks of therapy in both the groups. In addition, Telmisartan showed more beneficial effects on lipid profile when compared to Enalapril. KEYWORDS Hypertension, Dyslipidemia, Lipid Profile, Telmisartan, Enalapril

Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of T-cell lymphoma associated with an aggressive clinical course and a worse prognosis. HSTCL develops in the setting of chronic immune suppression or immune dysregulation in up to 20% of cases and is most often characterized by spleen, liver, and bone marrow involvement. Diagnosis and management of HSTCL pose significant challenges given the rarity of the disease along with the absence of lymphadenopathy and poor outcome with conventional chemotherapy regimens. These Guidelines Insights focus on the diagnosis and treatment of HSTCL as outlined in the NCCN Guidelines for T-Cell Lymphomas.

Chronic myeloid leukemia (CML) is defined by the presence of Philadelphia chromosome (Ph) which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to aBCR-ABL1fusion gene. CML occurs in 3 different phases (chronic, accelerated, and blast phase) and is usually diagnosed in the chronic phase. Tyrosine kinase inhibitor therapy is a highly effective first-line treatment option for all patients with newly diagnosed chronic phase CML. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with chronic phase CML.

Eosinophilic disorders and related syndromes represent a heterogeneous group of neoplastic and nonneoplastic conditions, characterized by more eosinophils in the peripheral blood, and may involve eosinophil-induced organ damage. In the WHO classification of myeloid and lymphoid neoplasms, eosinophilic disorders characterized by dysregulated tyrosine kinase (TK) fusion genes are recognized as a new category termed, myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2. In addition to these aforementioned TK fusion genes, rearrangements involving FLT3 and ABL1 genes have also been described. These new NCCN Guidelines include recommendations for the diagnosis, staging, and treatment of any one of the myeloid/lymphoid neoplasms with eosinophilia (MLN-Eo) and a TK fusion gene included in the 2017 WHO Classification, as well as MLN-Eo and a FLT3 or ABL1 rearrangement.

Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).

In the last decade, a better understanding of the molecular pathogenesis of B-cell non-Hodgkin lymphomas has resulted in the development of novel targeted therapies, such as small molecule inhibitors of select kinases in the B-cell receptor pathway, antibody-drug conjugates, and small molecules that target a variety of proteins (eg, CD-19, EZH2, and XPO-1-mediated nuclear export). Anti-CD19 CAR T-cell therapy, first approved for relapsed/refractory (R/R) diffuse large B-cell lymphoma, has also emerged as a novel treatment option for R/R follicular lymphoma and mantle cell lymphoma. These NCCN Guideline Insights highlight the new targeted therapy options included in the NCCN Guidelines for B-Cell Lymphomas for the treatment of R/R disease.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

The study presents an analysis of thermal diffusion and diffusion thermoeffects on the heat and mass transfer by natural convection of saturated non-Newtonian Sutterby fluid past a stretching surfa...

Numerical simulation is performed for mixed convective heat transfer past a sphere with uniform heat flux (Isoflux) thermal boundary condition for liquid metals. The steady, incompressible, laminar...

Diffuse large B-cell lymphomas (DLBCLs) and follicular lymphoma (FL) are the most common subtypes of B-cell non-Hodgkin’s lymphomas in adults. Histologic transformation of FL to DLBCL (TFL) occurs in approximately 15% of patients and is generally associated with a poor clinical outcome. Phosphatidylinositol 3-kinase (PI3K) inhibitors have shown promising results in the treatment of relapsed/refractory FL. CAR T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel) has emerged as a novel treatment option for relapsed/refractory DLBCL and TFL. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines for B-Cell Lymphomas regarding the treatment of TFL and relapsed/refractory FL and DLBCL.

Numerical simulation of the flow and forced convective heat transfer past a horizontal flat plate for liquid metals has b een performed in elliptical cylindrical coordinates. The two dimensional, s...

Mastocytosis is a group of heterogeneous disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin and/or in various extracutaneous organs. Systemic mastocytosis is the most common form of mastocytosis diagnosed in adults, characterized by mast cell infiltration of one or more extracutaneous organs (with or without skin involvement). The identification of KIT D816V mutation and the emergence of novel targeted therapies have significantly improved the diagnosis and treatment of systemic mastocytosis. However, certain aspects of clinical care, particularly the diagnosis, assessment, and management of mediator-related symptoms continue to present challenges. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with systemic mastocytosis.

In this paper, we numerically investigate the influence of Prandtl number on the thermo-fluidic transport characteristics for steady laminar mixed convection from a sphere in an assisting flow configuration. The stream function-vorticity formulation with a higher order finite difference compact scheme in spherical polar coordinates has been used to solve the governing transport equation of motion and thermal energy. The fluid flow and heat transfer characteristics are presented in terms of streamline and isotherm contours in close proximity to the sphere together with local Nusselt number along the sphere surface and average Nusselt number for the Reynolds number in the range 5 ≤ Re ≤ 200, Richardson number in the range 0 ≤ Ri ≤ 1.5 and Prandtl number ranging from 0.72 to 40. Critical Richardson number has been identified for different values of Reynolds number and Prandtl number, signifying the strength of the force of streamwise acceleration due to the buoyancy and externally imposed flow field relative to the combined viscous resistance and pressure force, for which the flow separation phenomenon occurring in the downstream region of the sphere gets suppressed. It reveals that for lower values of Reynolds number, the average Nusselt number monotonically increases with Richardson number for any particular value of Prandtl number. At higher values of Reynolds number, contrasting features have been observed. For lower values of Prandtl number, the average Nusselt number increases monotonically with Richardson number, while for higher values of Prandtl number the variation is non-monotonous.

Numerical simulation is conducted to study the forced convective heat transfer from an isoflux sphere for liquid metals. The flow is considered as steady, symmetric and incompressible with the fluids are Newtonian. The spherical geometry higher-order compact scheme (SGHOCS) has been applied to solve a nonlinear governing transport equation. The results of heat transfer characteristics are demonstrated in terms of local and average Nusselt number on the sphere surface by varying the parameters: Re (Reynolds number) from 1 to 200, for specific Pr (Prandtl number) of liquid metals, namely liquid sodium (Pr = 0.004), liquid gallium alloy (Pr = 0.0208) and liquid lithium (Pr = 0.065). The study reveals that the rate of heat transfer on the sphere surface is more for isoflux case when compared to the isothermal case. Furthermore, it is verified that as grid refines, the present results approach to fourth-order accuracy.

An investigation has been performed to study the influences of Soret and Dufour on steady, viscous dissipative Casson fluid flow along a linear stretching surface. Numerical solution of this problem is obtained by Spectral Relaxation Method. The outcomes are enumerated in terms of profiles of velocity, temperature, concentration, coefficients of skin friction, Nusselt and Sherwood numbers with reference to certain physical parameters. The results show that velocity reduces when there is an increase in Casson parameter. The Nusselt number enhances with Soret number whereas it decreases by enhancing Dufour number. Also, Nusselt number as well as Sherwood number increase with ratio parameter. Further, concentration profiles decrease because of increment in ratio parameter and Schmidt number, but they raise for higher Casson parameter and Soret number values.

All else equal, parasites that harm host fitness should depress densities of their hosts. However, parasites that alter host traits may increase host density via indirect ecological interactions. Here, we show how depression of infected host foraging rate can produce such a hydra effect. Using a foraging assay, we quantified reduced foraging rates of a zooplankton host infected with a virulent fungal parasite. We then parameterized a dynamical model of hosts, parasites, and resources with this foraging function, showing how foraging depression can create a hydra effect. Mathematically, the hydra arose when increased resource productivity exceeded any increase in resource consumption per host. Therefore, the foraging-mediated hydra effect more likely emerged (1) for hosts which strongly control logistic-like resources and (2) during larger epidemics of moderately virulent parasites. We then analyzed epidemics from 13 fungal epidemics in nature. We found evidence for a foraging-mediated hydra effect: large outbreaks depressed foraging rate and correlated with increased densities of both algae and hosts. Therefore, depression of foraging rate of infected hosts can produce higher host densities even during epidemics of parasites that increase host mortality. Such hydras might prevent collapse of host populations but also could produce higher densities of infected hosts.

Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).