Magic Bullet Research Articles

Antibody-Drug Conjugates for the Treatment of Renal Cancer: A Scoping Review on Current Evidence and Clinical Perspectives.

Antibody-drug conjugates (ADCs) are complex chemical structures composed of a monoclonal antibody, serving as a link to target cells, which is conjugated with a potent cytotoxic drug (i.e., payload) through a chemical linker. Inspired by Paul Ehrlich's concept of the ideal anticancer drug as a "magic bullet", ADCs are also highly specific anticancer agents, as they have been demonstrated to recognize, bind, and neutralize cancer cells, limiting injuries to normal cells. ADCs are among the newest pharmacologic breakthroughs in treating solid and hematologic malignancies. Indeed, in recent years, various ADCs have been approved by the Food and Drug Administration and European Medicines Agency for the treatment of several cancers, resulting in a "practice-changing" approach. However, despite these successes, no ADC is approved for treating patients affected by renal cell carcinoma (RCC). In the present paper, we thoroughly reviewed the current literature and summarized preclinical studies and clinical trials that evaluated the activity and toxicity profile of ADCs in RCC patients. Moreover, we scrutinized the potential causes that, until now, hampered the therapeutical success of ADCs in those patients. Finally, we discussed novel strategies that would improve the development of ADCs and their efficacy in treating RCC patients.

Is Discussing Controversial Issues in RE a Magic Bullet to Promote Social Cohesion? Mapping Opportunities and Challenges Based on Previous Research

Abstract In the public debate, it is often argued that RE is important because it promotes social cohesion. In the academic debate, however, this position is controversial because, firstly, this goal is associated with a politicization of RE and, secondly, empirical evidence on whether or how RE causes this effect seems to be lacking. In this article, I argue first that cohesion is an adequate subgoal of RE, assuming a social rather than a state-political understanding of cohesion. Second, I refer to international studies on teaching controversial issues (CIs), which show that students can learn participation, tolerance, and common good orientation through high-quality exploration of CIs in class. However, due to methodological difficulties and negative side effects, the discussion of CIs in RE cannot be assumed to be a magic bullet for achieving cohesion. For instance, uncertainties and ambiguities accompany forms of dissent in the classroom, which may lead to authoritarian dispositions and political intolerance. In addition, there are particular challenges for inclusive and especially denominational RE in terms of teachers, issues, students, and external factors.

Temperature monitoring in cardiac surgery with transesophageal echocardiography probe: magic bullet or underutilization of a powerful tool?

Temperature monitoring in cardiac surgery with transesophageal echocardiography probe: magic bullet or underutilization of a powerful tool?

PEG: The Magic Bullet for Biophysical Analysis of Highly Aggregating Small Molecules in Aqueous Solutions.

Biophysical research plays a crucial role in drug discovery, but many druglike molecules are poorly soluble and prone to aggregation, making their analysis challenging and susceptible to artifacts. To address this issue, we propose an approach that uses poly(ethylene glycol) (PEG) as an excipient in aqueous buffers to reduce the propensity of small molecules to aggregate. We show how PEG allows us to measure the thermodynamics of a complex formed by a heterobifunctional Small Molecule (hSM) that brings two proteins together. Our model accounts for all of the equilibrium states of the small molecule in solution, resulting in more precise parameters for describing how the proteins and the ligand interact. These precise parameters are important for designing better lead molecules.

Lifestyle medication vitamin D. What evidence is available?

An undersupply of 25-(OH) vitamin D3 (calcifediol) exists in many countries with moderate sunlight, long winters and only moderate fish consumption. Risk groups for vitamin D3 deficiency are older persons over 65years, geriatric persons in nursing homes, infants and children/adolescents. Therefore, there are also many situations in Germany which justify vitamin D substitution; however, vitamin D3 is currently praised as a "magic bullet" against everything. But what do the data look like? Where can it help and where can it not help?

Antibody-Drug Conjugates for Breast Cancer Treatment: Emerging Agents, Targets and Future Directions.

To achieve the scheme of "magic bullets" in antitumor therapy, antibody-drug conjugates (ADCs) were developed. ADCs consist of antibodies targeting tumor-specific antigens, chemical linkers, and cytotoxic payloads that powerfully kill cancer cells. With the approval of ado-trastuzumab emtansine (T-DM1) and fam-trastuzumab deruxtecan (T-DXd), the therapeutic potentials of ADCs in breast cancer have come into the spotlight. Nearly 30 ADCs for breast cancer are under exploration to move targeted therapy forward. In this review, we summarize the presenting and emerging agents and targets of ADCs. The ADC structure and development history are also concluded. Moreover, the challenges faced and prospected future directions in this field are reviewed, which give insights into novel treatments with ADCs for breast cancer.

Coupled Oscillators in an Agroecosystem: Integrating Direct and Indirect Effects.

AbstractAgricultural pests are increasingly appreciated as subjects of ecology. One particular case, a pest in coffee production, is analyzed here using the conceptual framework of complex systems, increasingly acknowledged as having an obvious home in the field of ecology, notorious for its complex structures. The particular case analyzed here arguably falls under the control of the complexity of the ecological system rather than of a simple magic bullet of population regulation. The system, which has been under study in southern Mexico for the past quarter century, is analyzed through the lens of neutral oscillations of the classical nondissipative Lotka-Volterra system. Based on three consumer/resource pairs (populations of [1] an ant, [2] a scale insect, [3] a beetle predator of the scale insect, [4] a fungal pathogen of the scale insect, and [5] a fly parasitoid of the ant), this five-dimensional system is well known qualitatively. Coupling all agents through both direct effects and trait-mediated indirect effects, the behavior of the neutral oscillation form of the system reveals a complex set of behaviors, including harmonized invariant sets, chaos, and/or quasiperiodicity. Such behaviors are well-known subjects in the science of complex systems and, it is argued, are ultimately sufficient to effect a degree of regulation on the pest, independent of explicit density-dependent feedback. Control of the system is thus seen as arguably actuated through its complexity, independent of any classic dissipative force.

Global Health Interventions: The Military, the Magic Bullet, the Deterministic Model—and Intervention Otherwise

“Intervention” is central to global health, but the significance and effects of how intervention is practiced are often taken for granted. This review takes interventions into health and medicine as subjects for ethnographic inquiry. We highlight three lines of anthropological contributions: studies of global health interventions that serve imperial and military objectives, studies of “magic bullet” interventions arising from laboratory science, and studies of interventions based on deterministic modeling techniques. We then outline examples of “intervention otherwise,” in which people build relations of solidarity and care through global health programming, design interventions to be interactive and adaptable, and use data and modeling to support health justice. Whereas many global health interventions reproduce Western power hierarchies, intervention otherwise draws attention to alternative forms of knowledge, action, and expertise. Our analysis of lively and multivalent practices of intervention has implications for debates about the im/possibility of decolonizing global health.

New care models for older adults seeking emergency care

New care models for older adults seeking emergency care Professors Katie Robinson and Rose Galvin from the Ageing Research Centre at the University of Limerick describe research on new models of care for older adults seeking emergency care. Research notes that emergency department crowding leads to long waiting times, treatment delays, increased costs, staff burnout and reduced patient satisfaction. While the problem of emergency department crowding is multifaceted and complex, and no magic bullet will resolve the issue, researchers at the Ageing Research Centre UL are exploring how new modes of care for older adults seeking emergency care can improve their overall care experience and clinical outcomes while reducing unscheduled care use. Analysing two trials, the OPTIMEND randomised controlled trial and the ED PLUS pilot trial, the University of Limerick plans to establish what outcomes should be evaluated in ED studies with older adults. They will also be working to develop standards of care for frail older adults attending the ED and a larger-scale evaluation of ED PLUS as well.

Is lirentelimab the "magic bullet" to fight pathological mast cell activation in systemic mastocytosis?

Is lirentelimab the "magic bullet" to fight pathological mast cell activation in systemic mastocytosis?

From the magic bullet to nanotechnology: nanoantimicrobials as therapeutics to fight multidrug-resistant microorganisms

From the magic bullet to nanotechnology: nanoantimicrobials as therapeutics to fight multidrug-resistant microorganisms

Corrigendum to: Searching for the Magic Bullet: Anticancer Platinum Drugs Which Can Be Accumulated or Activated in the Tumor Tissue.

An article was published in the journal "Anti-Cancer Agents in Medicinal Chemistry", Volume 7, No. 01, 2007, pp: 55-73 [1]. The first author is requesting an alteration in the name. Details of a correction are provided here. The original name published was Markus Galanski. The request is to change the name to Mathea Sophia Galanski. The original article can be found online at: https://www.eurekaselect.com/article/3359.

Emergence of Third Generation Tetracyclines: New Magic Bullets to Tackle Antibiotic Resistance in the Post-antibiotic Era

Tetracyclines are broad-spectrum antibiotics effective against a wide variety of microorganisms including bacteria, both Gram-positive and Gram-negative, mycoplasmas, rickettsiae, chlamydiae, and protozoan parasites. Owing to their broad-spectrum antimicrobial activities and inexpensiveness, tetracyclines have been used extensively in both human and animal infections and in animal feed as growth promoters. Owing to this, the global prevalence of antibiotic resistance, particularly of tetracyclines, for Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae and Gram-negative extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella species is high. Indeed, the acquisition of tetracycline-specific resistance genes, mutations within the ribosomal binding site, and/or chromosomal mutations lead to both class-specific and intrinsic antimicrobial resistance (AMR) mechanisms. As drug resistance increases globally, rendering diseases difficult to manage and eventually to mortality, antibiotics are becoming progressively less effective. Therefore, the discovery and development of novel antibiotics with appropriate indications is of the utmost importance. Among all antibiotics, the tetracyclines have acquired much attention due to the optimization of their chemical structures that paved the way to develop and introduce modern tetracyclines, referred to as third generation, namely tigecycline in the recent past, followed by omadacycline, eravacycline, and sarecycline very recently. Intriguingly, these novel tetracyclines are unique in two ways, first, these are highly effective against pathogens that acquired tetracycline-class resistance, and second, these agents exhibit either narrow or broad spectrum of in vitro activity against Gram-positive, Gram-negative, anaerobic, and atypical pathogens, including many drug-resistant strains lead to approval for limited use and unique indications. These beneficial effects represent a new era in the rational use of newer tetracyclines, the new magic bullets to tackle AMR in the post-antibiotic era. The present review focuses on third-generation tetracyclines emphasizing their safety, efficacy, and therapeutic choices in various clinical conditions of in-patient and out-patient settings.

Coevolution of species colonisation rates controls food-chain length in spatially structured food webs.

How the complexity of food webs depends on environmental variables is a long-standing ecological question. It is unclear though how food-chain length should vary with adaptive evolution of the constitutive species. Here we model the evolution of species colonisation rates and its consequences on occupancies and food-chain length in metacommunities. When colonisation rates can evolve, longer food-chains can persist. Extinction, perturbation and habitat loss all affect evolutionarily stable colonisation rates, but the strength of the competition-colonisation trade-off has a major role: weaker trade-offs yield longer chains. Although such eco-evo dynamics partly alleviates the spatial constraint on food-chain length, it is no magic bullet: the highest, most vulnerable, trophic levels are also those that least benefit from evolution. We provide qualitative predictions regarding how trait evolution affects the response of communities to disturbance and habitat loss. This highlights the importance of eco-evolutionary dynamics at metacommunity level in determining food-chain length.

NUTRIENT`S POCKET GAMES THE EFFECTIVENESS OF INTERACTIVE MEDIA IN UNDERSTANDING CHILD NUTRITION IN KEDUNGPEDARINGAN II KEPANJEN ELEMENTARY SCHOOL STUDENTS

Child nutrition is important for children's physical and cognitive development. However,
 many children do not have a good understanding of child nutrition. Interactive media has the potential
 to be an effective tool to teach children about child nutrition. This study aims to determine the
 effectiveness of interactive media (Game Saku Gizi) in improving students' understanding of child
 nutrition. This study used a pre-experimental research design with a one-group pretest-posttest design.
 The participants of this study were a group of grade 1 to grade 5 elementary school students at SDN
 Kedungpedaringan II Kepanjen, Indonesia. The results showed that there was a significant difference
 in students' understanding of child nutrition between the pretest and posttest. This means that the useof interactive media (Game Saku Gizi) can improve students' understanding of child nutrition. Thefindings of this study have important implications for the use of interactive media in education.Interactive media can be used to develop educational games and simulations that can help students to learn about various topics, including child nutrition. However, it is important to note that interactivemedia is not a magic bullet. It is important to use interactive media along with other teaching methods,such as lectures and discussions. In addition, it is also important to choose interactive media that isappropriate for the age and learning level of the students. Based on the results of the study, it can beconcluded that the Nutritional Pocket Game can improve the nutritional knowledge of students of

Past, present, and future options for right ventricular outflow tract reconstruction.

The pulmonary valve is the most frequently replaced cardiac valve in congenital heart diseases. Whether the valve alone or part of the right ventricular outflow tract have to be repaired or replaced depends on the specific pathological anatomy of the malformation. Once the decision to replace the pulmonary valve has been made, two options are available: the isolated transcatheter pulmonary valve replacement and the surgical implantation of a prosthetic valve either isolated or in combination with a procedure on the right ventricular outflow tract. In this paper, we will focus on the different past and present surgical options and present a new concept called "endogenous tissue restoration," a promising alternative to the hitherto existing implants. From a general point of view, neither the transcatheter nor the surgical valvular implants are magic bullets in the arsenal for the management of valvular diseases. Smaller valves have to be frequently replaced because of outgrowth of the patients, larger tissue valves may present late structural valve deterioration, while xenograft and homograft conduits may calcify and therefore become narrowed within unpredictable incidence and interval following implantation. Based on long-term research efforts combining the knowledge of supramolecular chemistry, electrospinning, and regenerative medicine, endogenous tissue restoration has emerged most recently as a promising option to create long-term functioning implants. This technology is appealing because following resorption of the polymer scaffold and timely replacement through autologous tissue, no foreign material remain at all in the cardiovascular system. Proof-of-concept studies as well as small first-in-man series have been completed and have demonstrated favorable anatomic and hemodynamic results, comparable to currently available implants in the short term. Based on the initial experience, important modifications to improve the pulmonary valve function have been initiated.

THE CIRCULAR ECONOMY: A Slippery Step on the Path to Sustainability?

Kieren Mayers, Tom Davis, and Luk N. Van Wassenhove explain how the unquestioning adoption of the circular economy approach to sustainable resource use will lead us to unintended environmental consequences. There is no magic bullet; wise use of the earth’s resources requires us to embrace the complexity of our industrial ecosystems and more carefully account for our impact on a case-by-case basis.

Competency Frameworks in the South African Public Service: The Wrong Magic Bullets?

Competency Frameworks in the South African Public Service: The Wrong Magic Bullets?

A modular systematic review of antenatal interventions targeting modifiable environmental exposures in improving low birth weight

BackgroundLow birth weight (LBW) increases the risk of short- and long-term morbidity and mortality from early life to adulthood. Despite research effort to improve birth outcomes the progress has been slow. ObjectiveThis systematic search and review of English language scientific literature on clinical trials aimed to compare the efficacy antenatal interventions to reduce environmental exposures including a reduction of toxins exposure, and improving sanitation, hygiene, and health-seeking behaviors, which target pregnant women to improve birth outcomes. MethodsWe performed eight systematic searches in MEDLINE (OvidSP), Embase (OvidSP), Cochrane Database of Systematic Reviews (Wiley Cochrane Library), Cochrane Central Register of Controlled Trials (Wiley Cochrane Library), CINAHL Complete (EbscoHOST) between 17 March 2020 and 26 May 2020. ResultsFour documents identified describe interventions to reduce indoor air pollution: two randomised controlled trials (RCTs), one systematic review and meta-analysis (SRMA) on preventative antihelminth treatment and one RCT on antenatal counselling against unnecessary caesarean section. Based on the published literature, interventions to reduce indoor air pollution (LBW: RR: 0.90 [0.56, 1.44], PTB: OR: 2.37 [1.11, 5.07]) or preventative antihelminth treatment (LBW: RR: 1.00 [0.79, 1.27], PTB: RR: 0.88 [0.43, 1.78]) are not likely to reduce the risk of LBW or Preterm birth (PTB). Data is insufficient on antenatal counselling against caesarian-sections. For other interventions, there is lack of published research data from RCTs. ConclusionsWe conclude that there is a paucity of evidence from RCT on interventions that modify environmental risk factors during pregnancy to potentially improve birth outcomes. Magic bullets approach might not work and that it would be important to study the effect of the broader interventions, particularly in LMIC settings. Global interdisciplinary action to reduce harmful environmental exposures, is likely to help to reach global targets for LBW reduction and sustainably improve long-term population health.

Venous air embolism in pediatric spine surgeries: Adrenaline as the magic bullet?

Venous air embolism in pediatric spine surgeries: Adrenaline as the magic bullet?