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Background: One of the causes of maternal and infant mortality is childbirth that still occurs at home with inadequate health facilities. Delivery at adequate health care facilities can reduce Mother Mortality Rate and Infant Mortality Rate. Objectives: This study aims to analyze the effect of antenatal care, family support and health support of workers regarding a place of delivery choice based on the MCH Revolution in working area of Sikumana Health Center, Kupang. Methods: This study used a case control design. The sample size of the case group was 30 women who gave birth in non-adequate health facilities and the control group was 30 women who gave birth in adequate health facilities. The sample collected by random sampling technique and used direct interview and questionnaire. Data analysis was carried out using Chi Square statistical test. Results: The results of the analysis indicated that from the studied variables, variables that influenced the choice of labor place were the mother's attitude (p = 0.000), and the history of previous place (p = 0.038), while the variable of mother's age did not affect (p = 0.778). Conclusion: The mother's attitude and previous delivery history had an effect on the choice of labor place, while the mother's age did not have any effect. These risk factors are expected to be a special concern for health workers in providing counseling for pregnant women in determining the place of labor. In addition, intense support from health workers is needed to motivate mothers and families to choose adequate health facilities as a place of labor.

This paper aims to focus on the current developments of Microwave Hybrid Heating (MHH) as a promising alternative method in soldering, characterization of solder joint properties related to the MHH and comparison with the conventional methods. A brief introduction to conventional heating, microwave heating and the concept of MHH in soldering is described in the earlier topic of this review. Further investigation on wettability, phase, and structural evaluation, interfacial intermetallic compounds (IMC) morphology, and tensile properties are presented and discussed in parallel with previous work (in the last decade) and the current works. The essential value of this review is to provide an in-depth understanding of MHH for an alternative soldering approach by compiling all the most recent research, technical setup, and key discoveries. This helps the electronic packaging sector, which is dealing with difficulties in meeting the growing demands for downsizing and adding multifunctionality in a single electronic device. Hence, any necessary advancement in this sector will help in future efforts to advance the soldering industry.

Access to learning that is not limited by space and time must continue even though during the COVID-19 emergency, lecturers and students are required to prepare devices for learning from home and PGRI Palembang University has facilitated by using an application called E-Learning Sisfo. Although the use of e-learning as a learning medium in higher education is not yet optimal, it has become one of the interesting things to be researched so that a study was conducted to determine the perceptions of students of the Accounting Education Study Program in using SISFO. E-learning network application at FKIP PGRI Palembang University. The sample in this study is a student majoring in Accounting who uses e-learning in the lecture process where data is collected by means of a questionnaire or questionnaire and analyzed using the regression method. The results of the regression test show that the perception of students of the Accounting Education Study Program. Based on the results of the study, it can be concluded that the perception of students of the Accounting Education Study Program in using the e-learning application SISFO at PGRI Palembang University is an average of seventy three point fifty percent in the high category. and have good motivation in using e-learning as a learning medium.

Microwave hybrid heating (MHH) is a possible approach for soldering; yet, the long-term reliability of solder joints is still unclear. In this work, a comparative study was carried out on the influence of isothermal aging on SAC305/Cu solder joints by conventional reflow and MHH. The conventional reflow oven was set to 260 °C at 60 s holding time, and MHH was carried out at high operating power at 40 s. The reflowed sample was isothermally aged at 150 °C for various aging times (0, 240, 480 and 960 h) in a laboratory oven. The conventional reflow and MHH transformed the IMC structure from scallop-like to a planar-like Cu6Sn5 with a linear increase in thickness and a thin layer of Cu3Sn was observed at 240 h of aging. While Ag3Sn particles grew larger at longer aging time. The MHH shows a thinner Cu6Sn5 layer, and a smaller grain size compared to conventional reflow. The ultimate tensile strength (UTS) for conventional reflow (32.7 MPa) is 26.8% lower compared to MHH (44.7 MPa). The UTS for MHH is greater than conventional reflow as the isothermal aging time increases.

Etoricoxib is a non-steroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation. The objective of the current study was to develop a sensitive, fast and high-throughput HPLC-ESI-MS/MS method to measure etoricoxib levels in human plasma using a one-step methanol protein precipitation technique. A tandem mass spectrometer equipped with an electrospray ionization (ESI) source operated in a positive mode and multiple reaction monitoring (MRM) were used for data collection. The quantitative MRM transition ions were m/z 359.15 > 279.10 and m/z 363.10 > 282.10 for etoricoxib and IS. The linear range was from 10.00 to 4000.39 ng/mL and the validation parameters were within the acceptance limits of the European Medicine Agency (EMA) and Food and Drug Analysis (FDA) guidelines. The present method was sensitive (10.00 ng/mL with S/N > 40), simple, selective (K prime > 2), and fast (short run time of 2 min), with negligible matrix effect and consistent recovery, suitable for high throughput analysis. The method was used to quantitate etoricoxib plasma concentrations in a bioequivalence study of two 120 mg etoricoxib formulations. Incurred sample reanalysis results further supported that the method was robust and reproducible.

This work describes the development of a new methodology based on magnetic nanoparticles assisted dispersive liquid–liquid microextraction (DLLME-MNPs) for preconcentration and extraction of chloramphenicol (CAP) antibiotic residues in water. The approach is based on the use of decanoic acid as the extraction solvent followed by the application of MNPs to magnetically retrieve the extraction solvent containing the extracted CAP. The coated MNPs were then desorbed with methanol, and the clean extract was analysed using ultraviolet–visible spectrophotometry. Several important parameters, such as the amount of decanoic acid, extraction time, stirring rate, amount of MNPs, type of desorption solvent, salt addition and sample pH, were evaluated and optimized. Optimum parameters were as follows: amount of decanoic acid: 200 mg; extraction time: 10 min; stirring rate: 800 rpm; amount of MNPs: 60 mg; desorption solvent: methanol; salt: 10%; and sample pH, 8. Under the optimum conditions, the method demonstrated acceptable linearity (R2 = 0.9933) over a concentration range of 50–1000 µg l–1. Limit of detection and limit of quantification were 16.5 and 50.0 µg l–1, respectively. Good analyte recovery (91–92.7%) and acceptable precision with good relative standard deviations (0.45–6.29%, n = 3) were obtained. The method was successfully applied to tap water and lake water samples. The proposed method is rapid, simple, reliable and environmentally friendly for the detection of CAP.

Research has been carried out on the process of natural sweeteners from the pulp of the “trembesi” fruit. The purpose of this study was to identify the types of sugar (fructose, glucose, sucrose) and to determine the effect of extraction temperature on the characteristics of natural sweeteners from “trembesi” pulp. This study used a simple completely randomized design (CRD) with extraction temperature treatments (60°C, 70°C, 80°C, 90°C and 100°C). The data obtained were analyzed using the Analysis of Variance (ANOVA) method, if there was a significant difference between treatments, it was continued with Duncan's Test (DMRT). The results of the research, it is known that the pulp of the tamarind fruit contains a total of 53.65% sugar; fructose 20.55%; glucose 12.77%; sucrose 18.21%; water content 25.739%; ash 2.771%; 1.226% protein; fat 7.028%; and carbohydrates 63.196%. The best treatment is the extraction temperature of 100°C; which produces natural sweeteners with the following characteristics: viscosity 11.71 cp; and sensories of viscosity 4.1. Total sugar in natural sweetener from pulp of the “trembesi” fruit 73.36%; fructose 26.40%; glucose 12.11%; and 25.4% sucrose.

A ground penetrating radar (GPR) survey was done across the Bok Bak Fault zone in Baling, Kedah in order to investigate the shallow subsurface geology of the Bok Bak fault zone, its extension and associated weak zones within the study area. GPR data acquisition was compared with visual inspection on the slope of the outcrop. Ten GPR profiles were acquired using 250 MHz GPR frequency. Basic data processing and filtering to reduce some noise and unwanted signal was done using MALA RAMAC Ground Vision software. The data penetrate around 2 meters in depth for all survey lines. In most lines shows clear images of shallowest Bok Bak Fault (NW trending) as detected at distance of 28 m horizontal marker. It also exhibits several sets of faults as a result of Bok Bak Fault deformation, including the conjugate NE trending fault (Lubok Merbau Fault). Active seismicity encompasses the Malay-Thai Peninsular trigger the changes of Bok Bak Fault dipping direction, steeper dips of conjugate faults and faults or fractures rotational movement.

Computer as a tool that is widely used human beings, it also raises occupational diseases as well as the use of machine in industry. Vision problems caused bye the use of computers, the American Optometric Association (AOA) called Computer Vision Syndrome (CVS) as a compound eye problems related to employment experienced by a person at close range as or related to computer use. The purpose of this study was to analyze the relationship between the working length, the distance eye with the monitor, lighting intensity, work attitude, and identifity the incidence of complaints of CVS workers experienced computer rentals. This study used Cross Sectional approach. Number of population and sample of 36 peoples working computer rental in the area Unnes campus. The instruments used in the form of quetionnatires, meter, and Lux meter. Chi square test result : (1)the working length (p=0,005); (2) the distance eye with the monitor (p=0,012); (3) lighting intensity (p=0,001); (4) work attitude (p=0,014) with complaints of CVS in workers computer rental at the campus Unnes. Suggestion for worker is to check their eyes regulary to the doctor if the complaints of CVS in order to minimize the occurrence of more severe diseases. While other researchers needed for further studies with different variables to better determine other factors associated with symptoms of Computer Vision Syndrome (CVS).

Adenosine is an immunosuppressive factor that limits anti-tumor immunity through the suppression of multiple immune subsets including T cells via activation of the adenosine A 2A receptor (A 2A R). Using both murine and human chimeric antigen receptor (CAR) T cells, here we show that targeting A 2A R with a clinically relevant CRISPR/Cas9 strategy significantly enhances their in vivo efficacy, leading to improved survival of mice. Effects evoked by CRISPR/Cas9 mediated gene deletion of A 2A R are superior to shRNA mediated knockdown or pharmacological blockade of A 2A R. Mechanistically, human A 2A R-edited CAR T cells are significantly resistant to adenosine-mediated transcriptional changes, resulting in enhanced production of cytokines including IFNγ and TNF, and increased expression of JAK-STAT signaling pathway associated genes. A 2A R deficient CAR T cells are well tolerated and do not induce overt pathologies in mice, supporting the use of CRISPR/Cas9 to target A 2A R for the improvement of CAR T cell function in the clinic.

Chimeric antigen receptor (CAR) T cell therapy has been highly successful in hematological malignancies leading to their US Food and Drug Administration (FDA) approval. However, the efficacy of CAR T cells in solid tumors is limited by tumor-induced immunosuppression, leading to the development of combination approaches, such as adjuvant programmed cell death 1 (PD-1) blockade. Current FDA-approved methods for generating CAR T cells utilize either anti-CD3 and interleukin (IL)-2 or anti-CD3/CD28 beads, which can generate a T cell product with an effector/exhausted phenotype. Whereas different cytokine preconditioning milieu, such as IL-7/IL-15, have been shown to promote T cell engraftment, the impact of this approach on CAR T cell responses to adjuvant immune-checkpoint blockade has not been assessed. In the current study, we reveal that the preconditioning of CAR T cells with IL-7/IL-15 increased CAR T cell responses to anti-PD-1 adjuvant therapy. This was associated with the emergence of an intratumoral CD8 + CD62L + TCF7 + IRF4 - population that was highly responsive to anti-PD-1 therapy and mediated the vast majority of transcriptional and epigenetic changes in vivo following PD-1 blockade. Our data indicate that preservation of CAR T cells in a TCF7 + phenotype is crucial for their responsiveness to adjuvant immunotherapy approaches and should be a key consideration when designing clinical protocols., (Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Adoptive cell therapies using genetically engineered T cell receptor or chimeric antigen receptor T cells are emerging forms of immunotherapy that redirect T cells to specifically target cancer. However, tumor antigen heterogeneity remains a key challenge limiting their efficacy against solid cancers. Here, we engineered T cells to secrete the dendritic cell (DC) growth factor Fms-like tyrosine kinase 3 ligand (Flt3L). Flt3L-secreting T cells expanded intratumoral conventional type 1 DCs and substantially increased host DC and T cell activation when combined with immune agonists poly (I:C) and anti-4-1BB. Importantly, combination therapy led to enhanced inhibition of tumor growth and the induction of epitope spreading towards antigens beyond those recognized by adoptively transferred T cells in solid tumor models of T cell receptor and chimeric antigen receptor T cell therapy. Our data suggest that augmenting endogenous DCs is a promising strategy to overcome the clinical problem of antigen-negative tumor escape following adoptive cell therapy.

Relapse after conventional chemotherapy remains a major problem in patients with myeloid malignancies such as acute myeloid leukemia (AML), and the major cause of death after diagnosis of AML is from relapsed disease. The only potentially curative treatment option currently available is allogeneic hematopoietic stem cell transplantation (allo-HSCT), which through its graft-vs.-leukemia effects has the ability to eliminate residual leukemia cells. Despite its long history of success however, relapse following allo-HSCT is still a major challenge and is associated with poor prognosis. In the field of adoptive therapy, CD19-targeted chimeric antigen receptor (CAR) T cells have yielded remarkable clinical success in certain types of B-cell malignancies, and substantial efforts aimed at translating this success to myeloid malignancies are currently underway. While complete ablation of CD19-expressing B cells, both cancerous and healthy, is clinically tolerated, the primary challenge limiting the use of CAR T cells in myeloid malignancies is the absence of a dispensable antigen, as myeloid antigens are often co-expressed on normal hematopoietic stem/progenitor cells (HSPCs), depletion of which would lead to intolerable myeloablation. This review provides a discussion on the current state of CAR T cell therapy in myeloid malignancies, limitations for clinical translation, as well as the most recent approaches to overcome these barriers, through various genetic modification and combinatorial strategies in an attempt to make CAR T cell therapy a safe and viable option for patients with myeloid malignancies., (Copyright © 2020 Mardiana and Gill.)

Purpose: Response rates to immune checkpoint blockade (ICB; anti-PD-1/anti-CTLA-4) correlate with the extent of tumor immune infiltrate, but the mechanisms underlying the recruitment of T cells following therapy are poorly characterized. A greater understanding of these processes may see the development of therapeutic interventions that enhance T-cell recruitment and, consequently, improved patient outcomes. We therefore investigated the chemokines essential for immune cell recruitment and subsequent therapeutic efficacy of these immunotherapies., Experimental Design: The chemokines upregulated by dual PD-1/CTLA-4 blockade were assessed using NanoString-based analysis with results confirmed at the protein level by flow cytometry and cytometric bead array. Blocking/neutralizing antibodies confirmed the requirement for key chemokines/cytokines and immune effector cells. Results were confirmed in patients treated with immune checkpoint inhibitors using single-cell RNA-sequencing (RNA-seq) and paired survival analyses., Results: The CXCR3 ligands, CXCL9 and CXCL10, were significantly upregulated following dual PD-1/CTLA-4 blockade and both CD8 + T-cell infiltration and therapeutic efficacy were CXCR3 dependent. In both murine models and patients undergoing immunotherapy, macrophages were the predominant source of CXCL9 and their depletion abrogated CD8 + T-cell infiltration and the therapeutic efficacy of dual ICB. Single-cell RNA-seq analysis of patient tumor-infiltrating lymphocytes (TIL) revealed that CXCL9/10/11 was predominantly expressed by macrophages following ICB and we identified a distinct macrophage signature that was associated with positive responses to ICB., Conclusions: These data underline the fundamental importance of macrophage-derived CXCR3 ligands for the therapeutic efficacy of ICB and highlight the potential of manipulating this axis to enhance patient responses., (©2019 American Association for Cancer Research.)

Objectives: Investigation of variable response rates to cancer immunotherapies has exposed the immunosuppressive tumor microenvironment (TME) as a limiting factor of therapeutic efficacy. A determinant of TME composition is the tumor location, and clinical data have revealed associations between certain metastatic sites and reduced responses. Preclinical models to study tissue-specific TMEs have eliminated genetic heterogeneity, but have investigated models with limited clinical relevance., Methods: We investigated the TMEs of tumors at clinically relevant sites of metastasis (liver and lungs) and their impact on αPD-1/αCTLA4 and trimAb (αDR5, α4-1BB, αCD40) therapy responses in the 67NR mouse breast cancer and Renca mouse kidney cancer models., Results: Tumors grown in the lungs were resistant to both therapies whereas the same tumor lines growing in the mammary fat pad (MFP), liver or subcutaneously could be completely eradicated, despite greater tumor burden. Assessment of tumor cells and drug delivery in 67NR lung or MFP tumors revealed no differences and prompted investigation into the immune TME. Lung tumors had a more immunosuppressive TME with increased myeloid-derived suppressor cell infiltration, decreased T cell infiltration and activation, and decreased NK cell activation. Depletion of various immune cell subsets indicated an equivalent role for NK cells and CD8 + T cells in lung tumour control. Thus, targeting T cells with αPD-1/αCTLA4 or trimAb was not sufficient to elicit a robust antitumor response in lung tumors., Conclusion: Taken together, these data demonstrate that tissue-specific TMEs influence immunotherapy responses and highlight the importance in defining tissue-specific response patterns in patients., Competing Interests: The authors declare no conflict of interest., (© 2019 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

The development of new cancer immunotherapies including checkpoint blockade and chimeric antigen receptor (CAR) T cell therapy has revolutionized cancer treatment. CAR T cells have shown tremendous success in certain B cell malignancies, resulting in U.S. Food and Drug Administration (FDA) approval of this approach for certain types of leukemia and lymphoma. However, response rates against solid cancer have been less successful to date. Approaches to modulate the immunosuppressive tumor microenvironment including targeting checkpoint pathways, modulating metabolic pathways, and generating cytokine-producing T cells have led to considerable enhancement of adoptive T cell immunotherapy, first in preclinical models and now in patients. This review provides a discussion of the most recent strategies to enhance the efficacy of CAR T cell antitumor responses in solid cancers., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Adoptive cellular therapy involving genetic modification of T cells with chimeric antigen receptor (CAR) transgene offers a promising strategy to broaden the efficacy of this approach for the effective treatment of cancer. Although remarkable antitumor responses have been observed following CAR T-cell therapy in a subset of B-cell malignancies, this has yet to be extended in the context of solid cancers. A number of promising strategies involving reprogramming the tumor microenvironment, increasing the specificity and safety of gene-modified T cells and harnessing the endogenous immune response have been tested in preclinical models that may have a significant impact in patients with solid cancers. This review will discuss these exciting new developments and the challenges that must be overcome to deliver a more sustained and potent therapeutic response.

Immunotherapy is widely accepted as a powerful new treatment modality for the treatment of cancer. The most successful form of immunotherapy to date has been the blockade of the immune checkpoints PD-1 and CTLA-4. Combining inhibitors of both PD-1 and CTLA-4 increases the proportion of patients who respond to immunotherapy. However, most patients still do not respond to checkpoint inhibitors, and prognostic biomarkers are currently lacking. Therefore, a better understanding of the mechanism by which these checkpoint inhibitors enhance antitumor immune responses is required to more accurately predict which patients are likely to respond and further enhance this treatment modality. Our current study of two mouse tumor models revealed that CD4 + Foxp3 - cells activated by dual PD-1/CTLA-4 blockade modulated the myeloid compartment, including activation of conventional CD103 + dendritic cells (DC) and expansion of a myeloid subset that produces TNFα and iNOS (TIP-DCs). CD4 + Foxp3 - T cell-mediated activation of CD103 + DCs resulted in enhanced IL12 production by these cells and IL12 enhanced the therapeutic effect of dual PD-1/CTLA-4 blockade. Given the importance of these myeloid subsets in the antitumor immune response, our data point to a previously underappreciated role of CD4 + Foxp3 - cells in modulating this arm of the antitumor immune response. Cancer Immunol Res; 6(9); 1069-81. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Purpose: While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model. Experimental Design: In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100). We used a regimen of adoptive cell transfer incorporating vaccination (ACTIV), with recombinant vaccinia virus expressing gp100, to treat a range of tumors including orthotopic breast tumors and large liver tumors. Results: ACTIV therapy induced durable complete remission of a variety of Her2 + tumors, some in excess of 150 mm 2 , in immunocompetent mice expressing Her2 in normal tissues, including the breast and brain. Vaccinia virus induced extensive proliferation of T cells, leading to massive infiltration of T cells into tumors. Durable tumor responses required the chemokine receptor CXCR3 and exogenous IL2, but were independent of IFNγ. Mice were resistant to tumor rechallenge, indicating immune memory involving epitope spreading. Evidence of limited neurologic toxicity was observed, associated with infiltration of cerebellum by T cells, but was only transient. Conclusions: This study supports a view that it is possible to design a highly effective combination immunotherapy for solid cancers, with acceptable transient toxicity, even when the target antigen is also expressed in vital tissues. Clin Cancer Res; 23(10); 2478-90. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Adoptive immunotherapy utilizing chimeric antigen receptor (CAR) T cells has demonstrated high success rates in hematologic cancers, but results against solid malignancies have been limited to date, due in part to the immunosuppressive tumor microenvironment. Activation of the 4-1BB (CD137) pathway using an agonistic α-4-1BB antibody is known to provide strong costimulatory signals for augmenting and diversifying T-cell responses. We therefore hypothesized that a combination of α-4-1BB and CAR T-cell therapy would result in improved antitumor responses. Using a human-Her2 self-antigen mouse model, we report here that α-4-1BB significantly enhanced CAR T-cell efficacy directed against the Her2 antigen in two different established solid tumor settings. Treatment also increased the expression of IFNγ and the proliferation marker Ki67 in tumor-infiltrating CAR T cells when combined with α-4-1BB. Strikingly, α-4-1BB significantly reduced host immunosuppressive cells at the tumor site, including regulatory T cells and myeloid-derived suppressor cells, correlating with an increased therapeutic response. We conclude that α-4-1BB has a multifunctional role for enhancing CAR T-cell responses and that this combination therapy has high translational potential, given current phase I/II clinical trials with α-4-1BB against various types of cancer. Cancer Res; 77(6); 1296-309. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Chimeric antigen receptor (CAR) T cells have been highly successful in treating hematological malignancies, including acute and chronic lymphoblastic leukemia. However, treatment of solid tumors using CAR T cells has been largely unsuccessful to date, partly because of tumor-induced immunosuppressive mechanisms, including adenosine production. Previous studies have shown that adenosine generated by tumor cells potently inhibits endogenous antitumor T cell responses through activation of adenosine 2A receptors (A2ARs). Herein, we have observed that CAR activation resulted in increased A2AR expression and suppression of both murine and human CAR T cells. This was reversible using either A2AR antagonists or genetic targeting of A2AR using shRNA. In 2 syngeneic HER2+ self-antigen tumor models, we found that either genetic or pharmacological targeting of the A2AR profoundly increased CAR T cell efficacy, particularly when combined with PD-1 blockade. Mechanistically, this was associated with increased cytokine production of CD8+ CAR T cells and increased activation of both CD8+ and CD4+ CAR T cells. Given the known clinical relevance of the CD73/adenosine pathway in several solid tumor types, and the initiation of phase I trials for A2AR antagonists in oncology, this approach has high translational potential to enhance CAR T cell efficacy in several cancer types.