B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches.

Despite considerable advances in the treatment of multiple myeloma (MM) in the last decade, a substantial proportion of patients do not respond to current therapies or have a short duration of response. Furthermore, these treatments can have notable morbidity and are not uniformly tolerated in all patients. As there is no cure for MM, patients eventually become resistant to therapies, leading to development of relapsed/refractory MM. Therefore, an unmet need exists for MM treatments with novel mechanisms of action that can provide durable responses, evade resistance to prior therapies, and/or are better tolerated. B-cell maturation antigen (BCMA) is preferentially expressed by mature B lymphocytes, and its overexpression and activation are associated with MM in preclinical models and humans, supporting its potential utility as a therapeutic target for MM. Moreover, the use of BCMA as a biomarker for MM is supported by its prognostic value, correlation with clinical status, and its ability to be used in traditionally difficult-to-monitor patient populations. Here, we review three common treatment modalities used to target BCMA in the treatment of MM: bispecific antibody constructs, antibody-drug conjugates, and chimeric antigen receptor (CAR)-modified T-cell therapy. We provide an overview of preliminary clinical data from trials using these therapies, including the BiTE® (bispecific T-cell engager) immuno-oncology therapy AMG 420, the antibody-drug conjugate GSK2857916, and several CAR T-cell therapeutic agents including bb2121, NIH CAR-BCMA, and LCAR-B38M. Notable antimyeloma activity and high minimal residual disease negativity rates have been observed with several of these treatments. These clinical data outline the potential for BCMA-targeted therapies to improve the treatment landscape for MM. Importantly, clinical results to date suggest that these therapies may hold promise for deep and durable responses and support further investigation in earlier lines of treatment, including newly diagnosed MM

Dual energy CT - a possible new method to assess regression of rectal cancers after neoadjuvant treatment

BACKGROUND AND OBJECTIVES: The measurement of tumor regression after neoadjuvant oncological treatment has gained increasing interest because it has a prognostic value and because it may influence the method of treatment in rectal cancer. The assessment of tumor regression remains difficult and inaccurate with existing methods. Dual Energy Computed Tomography (DECT) enables qualitative tissue differentiation by simultaneous scanning with different levels of energy. We aimed to assess the feasibility of DECT in quantifying tumor response to neoadjuvant therapy in loco-advanced rectal cancer.METHODS: We enrolled 11 patients with histological and MRI verified loco-advanced rectal adenocarcinoma and followed up on them prospectively. All patients had one DECT scanning before neoadjuvant treatment and one 12 weeks after using the spectral imaging scan mode. DECT analyzing tools were used to determine the average quantitative parameters; effective-Z, water- and iodine-concentration, Dual Energy Index (DEI), and Dual Energy Ratio (DER). These parameters were compared to the regression in the resection specimen as measured by the pathologist.RESULTS: Changes in the quantitative parameters differed significantly after treatment in comparison with pre-treatment, and the results were different in patients with different CRT response rates.CONCLUSION: DECT might be helpful in the assessment of rectal cancer regression grade after neoadjuvant treatment.</p

THE VIRTUAL PUBLIC SPHERE: QUESTIONING THE STANDARDS OF FORMATION ACCORDING TO THE TRILOGY OF RECOGNITION BY AXEL HONNETH

This study aims to investigate the extent to which cyber space is able to host public sphere discussions based on public deliberation of issues of public affairs, communicative equality between social subjects. The study attempted to search for the trilogy of recognition (love, solidarity, right) by Axel Honeth and search for it within the cyber platforms that It is relied upon as an incubating environment for public affairs discussions and the formation of a virtual public sphere that seeks to achieve mutual recognition between interacting subjects

Jihad: liberation or terrorism? the thought of sayyid qutb

Magister Artium - MAIncludes bibliographic references (leaves 184-195)"In this thesis, I contrast Qutbs approach towards jihad with that which is found in the primary sources of Islam and as espoused by the proponents of the four schools of thought, as well as key Islamic scholars. This study also attempts to explore the conceptual confusion between terrorism, jihad, and legitimate defense and resistance by comparing the legislation on jihad in Islam with that which exists in international law and conventions. I then turn my attention to the focal point of this study, the writings of Sayyid Qutb on jihad...

Risks of uncertainty propagation in Al-augmented security pipelines

The use of AI technologies is percolating into the secure development of software-based systems, with an increasing trend of composing AI-based subsystems (with uncertain levels of performance) into automated pipelines. This presents a fundamental research challenge and poses a serious threat to safety-critical domains (e.g., aviation). Despite the existing knowledge about uncertainty in risk analysis, no previous work has estimated the uncertainty of AI-augmented systems given the propagation of errors in the pipeline. We provide the formal underpinnings for capturing uncertainty propagation, develop a simulator to quantify uncertainty, and evaluate the simulation of propagating errors with two case studies. We discuss the generalizability of our approach and present policy implications and recommendations for aviation. Future work includes extending the approach and investigating the required metrics for validation in the aviation domain

CIVILIZED COEXISTENCE IN THE HEAVENLY RELIGIONS: A HISTORICAL APPROACH AND A SOCIAL VISION IN THE REALITY OF THE TIMES

The true and pure monotheistic religions of distortions and positive texts emphasized the need for understanding, acquaintance and cooperation between people, but while recognizing the principle of difference between these races, and that is in the service of humanity and its interests, and the basis of that justice and equality, and we as Muslims ordered Islam and the Holy Quran, which God has saved from any distortion or falsification, to preserve that coexistence, and to set the ideals in coexistence with others and preserve their rights, and history is a testament to that and history. This framework includes the objectives of this article entitled: The message of civilized coexistence in the heavenly religions: a historical approach and a social vision in the reality of the times, the first part of which we try to focus on that noble message in all the heavenly religions and approach them through models witnessed by history; The strong dominated the weak and violated his sanctities and ate his rights, and the grinding wars and seditions that are prevalent nowadays are only the result of the interruption of the rope of coexistence and civilized communication, which was and still is The Pure Source Islam through the verses of the Holy Quran and the Prophet's Sunnah

Environmental impact reduction of precast multi-storey buildings by crescent-moon seismic dampers hidden in beam-column joints

The growing demand of sustainable precast structures for multi-storey con-structions is often driven by the optimisation of cross-sections and reinforcement volumes of the structural elements. The present paper describes a real building recently designed and assembled with the installation of crescent-moon hysteretic dampers in the beam-column joints, recently proposed and patented. The joint continuity allows for an optimisation of the lateral load resist-ing system, reducing the size of the columns with respect to the classical precast frame structural arrangement with hinged joints, whilst protecting columns and beams from the large actions deriving from the classical moment-resisting cast-in-situ or partially precast technological solu-tions. After the complete detailed design of the case study building employing the 3 solutions described above, the precast dissipative one being designed with dynamic non-linear analysis, the results of an environmental impact analysis are compared and discussed, confirming a reduced environmental impact for the dissipative solution, with respect to both precast with hinged beam-column joints and moment-resisting cast-in-situ alternatives