Immunotherapeutics and other anticancer agents in the management of advanced gastric cancer

Advanced gastric cancer (AGC) is characterized by high mortality. The survival is estimated as 14.2 months. The treat­ment of choice in the early stages of GC is surgery. Due to high potential of malignancy, postoperative chemotherapy is usually administered. Novel methods of treatment involve immunotherapeutic agents (IA). The new therapies seem to be a hopeful perspective for patients with advanced GC. In this review, we present the outcomes of clinical trials in GC treatment with IA and their mechanisms of action. Furthermore, we present the benefits and shortcomings of immunotherapy and describe potential directions for future research

Immunotherapeutics and other anticancer agents in the management of advanced gastric cancer

Advanced gastric cancer (AGC) is characterized by high mortality. The survival is estimated as 14.2 months. The treat­ment of choice in the early stages of GC is surgery. Due to high potential of malignancy, postoperative chemotherapy is usually administered. Novel methods of treatment involve immunotherapeutic agents (IA). The new therapies seem to be a hopeful perspective for patients with advanced GC. In this review, we present the outcomes of clinical trials in GC treatment with IA and their mechanisms of action. Furthermore, we present the benefits and shortcomings of immunotherapy and describe potential directions for future research

Leiomyosarcoma in adrenal gland

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The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) in axillary lymph nodes – a case report and review of 29 other cases from world literature

Introduction. Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALC) is a new disease established by the WHO in 2016. BIA-ALCL is one of the most severe adverse effects of breast augmentation or breast reconstruction with the use of silicone implants. Material and methods. In our report we present a case of a 46-year-old patient diagnosed with BIA-ALCL in the General and Oncological Surgery Clinic of the Pomeranian Medical University in Szczecin. This is one of the first described cases of this disease in Poland. Especially interesting is the fact that the lymphoma developed two years after the removal of the implants and the pathology occurred in the axillary lymph nodes. In order to compare the published case of BIA-ALCL we reviewed 29 cases from literature. Results. We described the most clinically relevant factors. The age range of females analysed with diagnosed BIA-ALCL is between 27 to 87 years. The time from implant insertion to the appearance of the first symptoms varies. The use of textured implants seems to be one of the most important risk factors of novel lymphoma. Conclusions. The patients with breast implants should be informed about the risk of BIA-ALCL and related symptoms. The number of articles about BIA-ALCL is minimal, therefore knowledge about the disease remains limited. There is a need to broaden knowledge about the pathological process, clinical manifestations, risk factors and medical tests crucial to achieve an accurate diagnosis.Introduction. Breast implant associated anaplastic large cell lymphoma (BIA-ALC) is a new disease established by the WHO in 2016. BIA-ALCL is one of the most severe adverse effects of breast augmentation or breast reconstruction with the use of silicone implants.  Material and methods. In our report we present a case of a 46-year-old patient diagnosed with BIA-ALCL in the General and Oncological Surgery Clinic of the Pomeranian Medical University in Szczecin. This is one of the first described cases of this disease in Poland. Especially interesting is the fact that the lymphoma developed two years after the removal of the implants and the pathology occurred in the axillary lymph nodes. In order to compare the published case of BIA-ALCL we reviewed 29 cases from literature.  Results. We described the most clinically relevant factors. The age range of females analysed with diagnosed BIA-ALCL is between 27 to 87 years. The time from implant insertion to the appearance of the first symptoms varies. The use of textured implants seems to be one of the most important risk factors of novel lymphoma.  Conclusions. The patients with breast implants should be informed about the risk of BIA-ALCL and related symptoms. The number of articles about BIA-ALCL is minimal, therefore knowledge about the disease remains limited. There is a need to broaden knowledge about the pathological process, clinical manifestations, risk factors and medical tests crucial to achieve an accurate diagnosis.

Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins

Background: The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing under‑ standing of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to chal‑ lenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic under‑ standing of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP). Main body: The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respira‑ tory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell–cell interac‑ tions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential. Conclusion: The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.org platform to expand the mechanistic data, improve the confidence in each of the proposed KE and key event relations (KERs), and allow for the identification of new, or refinement of established KE and KERs

Clinical manifestations of intermediate allele carriers in Huntington disease

Objective: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. Methods: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Results: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p 0.002). Conclusions: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. ClinicalTrials.gov identifier: NCT01590589