Counteractive Strategies Research Articles

Targeting undruggable phosphatase overcomes trastuzumab resistance by inhibiting multi-oncogenic kinases

AimsResistance to targeted therapy is one of the critical obstacles in cancer management. Resistance to trastuzumab frequently develops in the treatment for HER2+ cancers. The role of protein tyrosine phosphatases (PTPs) in trastuzumab resistance is not well understood. In this study, we aim to identify pivotal PTPs affecting trastuzumab resistance and devise a novel counteracting strategy. MethodsFour public datasets were used to screen PTP candidates in relation to trastuzumab responsiveness in HER2+ breast cancer. Tyrosine kinase (TK) arrays were used to identify kinases that linked to protein tyrosine phosphate receptor type O (PTPRO)-enhanced trastuzumab sensitivity. The efficacy of small activating RNA (saRNA) in trastuzumab-conjugated silica nanoparticles was tested for PTPRO upregulation and resistance mitigation in cell models, a transgenic mouse model, and human cancer cell line-derived xenograft models. ResultsPTPRO was identified as the key PTP which influences trastuzumab responsiveness and patient survival. PTPRO de-phosphorated several TKs, including the previously overlooked substrate ERBB3, thereby inhibiting multiple oncogenic pathways associated with drug resistance. Notably, PTPRO, previously deemed “undruggable,” was effectively upregulated by saRNA-loaded nanoparticles. The upregulated PTPRO simultaneously inhibited ERBB3, ERBB2, and downstream SRC signaling pathways, thereby counteracting trastuzumab resistance. ConclusionsAntibody-conjugated saRNA represents an innovative approach for targeting “undruggable” PTPs.

Prevalence of smoking habits, attitudes and knowledge on counteractive strategies among a sample of healthcare employees: results of the smoking-free health environments project in the province of Palermo, Italy.

Tobacco use is responsible for over 7 million deaths annually, making smoking the leading cause of preventable mortality globally. Over the last two decades in Italy, the prevalence of smoking among physicians has consistently decreased, while it remains higher and is gradually decreasing among non-physician healthcare workers. The aim of this study was to investigate the Prevalence of smoking habits, attitudes, and knowledge on counteractive strategies among employees in the Primary Healthcare Facilities in the Province of Palermo, Italy. A cross-sectional survey was conducted between June 2020 and December 2020 through a previously validated anonymous questionnaire structured in four sections including 34 items. Data were analyzed using Stata/MP 12.1 statistical software. Overall, 2,645 participants answered the questionnaire. The prevalence of either current or former smokers was 18.6%. Based on the multivariable analysis conducted, a significantly higher frequency of current smokers was observed among male participants (AdjOR: 1.29; CI95%: 1.02-1.64) and those belonging to the Surgical Unit (AdjOR: 1.92; CI95%: 1.27-2.90). Conversely, the prevalence of current smokers was significantly lower among those with at least one child (AdjOR: 0.67; CI95%: 0.49-0.91), with an educational qualification equal to or greater than a graduation degree (AdjOR: 0.56; CI95%: 0.43-0.73), those who considered second-hand smoke harmful (AdjOR: 0.06; CI95%: 0.008-0.60), those who had observed smoking or detected the smell of smoke in their workplace (AdjOR: 0.64; CI95%: 0.45-0.91). Furthermore, the prevalence of current smokers was significantly lower among participants who believed that healthcare professionals could play a crucial role in influencing their patients' lifestyles (AdjOR: 0.67; CI95%: 0.50-0.90) and among those who recommend their patients to quit smoking (AdjOR: 0.35; CI95%: 0.24-0.51). The results of the current research demonstrate that, despite the decline in smoking prevalence among physicians, the rate of smokers among healthcare facility employees remains unacceptably high. This underscores the need to re-evaluate current anti-tobacco strategies in the workplace.

Challenges and Counteracting Strategies Including Optimum Health Service Practices for Frontline Nurses During the Mpox Outbreak and Futuristic Vision.

Monkeypox (mpox) is an evolving infectious disease caused by the monkeypox virus (MPXV). On July 23, 2022, the WHO declared the recent mpox outbreaks a public health emergency of international concern (PHEIC), which terminated on May 11, 2023. As of July 11, 2023, 88,288 confirmed cases and 149 deaths have been reported from 112 countries and territories. Currently, mpox is not a PHEIC, as the outbreak and its impacts are nearly over. Nurses played significant roles during the mpox 2022 outbreak as frontline workers. In light of the impending mpox global outbreak in 2022, this brief report provides an update on the enormous difficulties faced by frontline nurses while playing a crucial role in handling the mpox outbreak and some potential solutions to these difficulties. The methodological framework employed in this narrative brief report involves conducting a comprehensive analysis and synthesis of relevant literature and hypothetical scenarios. The aim is to put forth practical strategies that can effectively tackle the difficulties encountered by frontline nurses in the context of the mpox outbreak. Additionally, the report seeks to envision a healthcare system that is more resilient in the face of future challenges. It is important to understand the challenges the nurses face from their perspective. As frontline health care workers, the various health issues of nurses and their concerns must be taken care of appropriately by adopting optimum health service practices, adequate safety measures, recommended precautionary measures, and boosting them mentally while handling mpox patients. Counseling and the arrangement of workshops are required. Appropriate care should be taken to address the various health issues concerning nurses by adopting health service practices at optimum levels. Side by side, recommended safety and precautionary measures should be followed.

Cyber threat intelligence practices in the national sphere of government in South Africa

Over the past two decades, cybercrime and cybercriminals have had a great impact on the safety, security and protection of the public sector’s confidential data and information assets. The increased usage of the internet and new, advanced 4IR technologies, and the digitisation of government’s public sector goods and services have become a growing concern to the government and its public sector institutions. In the South African context, as a developing country, it unfortunately lags behind advanced and developed nations in terms of fully counteracting cybercrime and cybercriminal operations. Despite this challenge, the South African government has been making tremendous efforts in combatting cybercrime. The aim of this article is to contextualise the study and practice of cyber threat intelligence at the national sphere of government in the South African public sector, namely, the former Department of Energy (DoE), former Department of Science and Technology (DST) and the former Department of Environmental Affairs (DEA) a qualitative research approach was followed using a case study approach. Primary data was collected through semi-structured interviews with senior departmental management. The findings are presented according to the Threat Intelligence Lifecycle analysis which serves as an analytical framework. The study concludes that in order to achieve effective cybersecurity practices and principles in the public sector , the government must identify the top trends commonly associated with cybersecurity to be able to develop and implement counteractive strategies and approaches, as well as to improve security systems and programs to ensure that an organisation is sufficiently prepared for and protected against cybercriminals and cyberattacks.

Cancer Cachexia: Underlying Mechanisms and Potential Therapeutic Interventions.

Cancer cachexia, a multifactorial metabolic syndrome developed during malignant tumor growth, is characterized by an accelerated loss of body weight accompanied by the depletion of skeletal muscle mass. This debilitating condition is associated with muscle degradation, impaired immune function, reduced functional capacity, compromised quality of life, and diminished survival in cancer patients. Despite the lack of the known capability of fully reversing or ameliorating this condition, ongoing research is shedding light on promising preclinical approaches that target the disrupted mechanisms in the pathophysiology of cancer cachexia. This comprehensive review delves into critical aspects of cancer cachexia, including its underlying pathophysiological mechanisms, preclinical models for studying the progression of cancer cachexia, methods for clinical assessment, relevant biomarkers, and potential therapeutic strategies. These discussions collectively aim to contribute to the evolving foundation for effective, multifaceted counteractive strategies against this challenging condition.

Hepatitis C Virus Disrupts Annexin 5-Mediated Occludin Integrity through Downregulation of Protein Kinase Cα (PKCα) and PKCη Expression, Thereby Promoting Viral Propagation.

Annexins (ANXs) comprise a family of calcium- and phospholipid-binding proteins and are implicated in the hepatitis C virus (HCV) life cycle. Here, we demonstrate a novel role of ANX5 in the HCV life cycle. Comparative analysis by quantitative PCR in human hepatoma cells revealed that ANX2, ANX4, and ANX5 were highly expressed among the ANX family proteins. Knockdown of ANX5 mRNA resulted in marked enhancement of HCV RNA replication but had no effect on either HCV translation or assembly. Using the HCV pseudoparticle (HCVpp) system, we observed enhancement of HCVpp infectivity in ANX5 knockdown Huh-7OK1 cells, suggesting that ANX5 is involved in suppression of HCV entry. Additionally, we observed that subcellular localizations of tight-junction proteins, such as claudin 1 (CLDN1) and occludin (OCLN), were disrupted in the ANX5 knockdown cells. It was reported that HCV infection was facilitated by disruption of OCLN distribution and that proper distribution of OCLN was regulated by its phosphorylation. Knockdown of ANX5 resulted in a decrease of OCLN phosphorylation, thereby disrupting OCLN distribution and HCV infection. Further analysis revealed that protein kinase C (PKC) isoforms, including PKCα and PKCη, play important roles in the regulation of ANX5-mediated phosphorylation and distribution of OCLN and in the restriction of HCV infection. HCV infection reduced OCLN phosphorylation through the downregulation of PKCα and PKCη expression. Taken together, these results suggest that ANX5, PKCα, and PKCη contribute to restriction of HCV infection by regulating OCLN integrity. We propose a model that HCV disrupts ANX5-mediated OCLN integrity through downregulation of PKCα and PKCη expression, thereby promoting HCV propagation. IMPORTANCE Host cells have evolved host defense machinery to restrict viral infection. However, viruses have evolved counteracting strategies to achieve their infection. In the present study, we obtained results suggesting that ANX5 and PKC isoforms, including PKCα and PKCη, contribute to suppression of HCV infection by regulating the integrity of OCLN. The disruption of OCLN integrity increased HCV infection. We also found that HCV disrupts ANX5-mediated OCLN integrity through downregulation of PKCα and PKCη expression, thereby promoting viral infection. We propose that HCV disrupts ANX5-mediated OCLN integrity to establish a persistent infection. The disruption of tight-junction assembly may play important roles in the progression of HCV-related liver diseases.

The emergence of the circulating vaccine-derived poliovirus type 2 in multiple countries requires active surveillance: current scenario and counteracting strategies.

Mohapatra, Ranjan K. MSc, MPhil, PhDa,; Kutikuppala, L.V. Simhachalam MBBSb; Seidel, Veronique PhDc; Ansari, Azaj PhDd; Mishra, Snehasish PhDe; Kandi, Venkataramana PhDf Author Information

Recent surge in cholera outbreaks globally during the COVID-19 pandemic era: a potential threat to the African continent and salient counteracting strategies.

Recent surge in cholera outbreaks globally during the COVID-19 pandemic era: a potential threat to the African continent and salient counteracting strategies.

MERS-CoV recently re-emerged in Qatar, Saudi Arabia, its feasible global health risks amid FIFA world cup 2022 and salient counteracting strategies - an update.

MERS-CoV recently re-emerged in Qatar, Saudi Arabia, its feasible global health risks amid FIFA world cup 2022 and salient counteracting strategies - an update.

Accurate photoactivation monitoring via the construction of an intramolecular synergistic counteracting mechanism of FRET and IFE.

The synergistic modulation of fluorescence resonance energy transfer (FRET) and the inner filter effect (IFE) was constructed within a molecule to control the stable fluorescence intensity as the internal standard, providing a new strategy for the accurate monitoring of photoactivation.

NUMERACY SKILL USE AMONG MIDDLE-AGED AND OLDER WORKERS IN THE US

Abstract In numeric information-rich societies, numeracy is essential both at work and in everyday life (e.g., calculating a budget). Numeracy skills generally decline with aging. Thus, among middle-aged and older workers, maintaining and improving numeracy skills is crucial to securing employment as well as managing everyday life. One of the counteracting strategies is to practice numeracy. However, little is known about how and what kinds of numeracy skills are used among older workers. We analyzed a nationally representative sample of U.S. workers aged 45 to 74 (n = 3,850) from the 2012/2014/2017 Program for International Assessment of Adult Competencies (PIAAC) restricted-use-file. Six dichotomous numeracy use indicators (e.g., calculating a budget, using advanced statistics) at work and in everyday life were considered. Survey weighted latent class analysis (LCA) identified three subgroups with distinctive numeracy skill use patterns, including ubiquitous (both at work and in everyday life) users, occupational users, and non-users. For example, calculating a budget was common both in non-users (40%) and ubiquitous users (84%), whereas uncommon among occupational users (25%). Also, only ubiquitous users practiced advanced math and statistics (14%), while others did not (nearly 0%). The subsequent regression analysis revealed that higher educational attainment, higher income, certain racial group (i.e., Whites), and better self-rated health were associated with greater numeracy skill use. The lack of numeracy skill use leads to lower skill levels and, in turn, social and economic disadvantages in later life. In addition to more detailed LCA results interpretations, possible policy and educational interventions are evaluated.

Mechanisms of CAR T cell exhaustion and current counteraction strategies.

The functional state of chimeric antigen receptor T (CAR T) cells determines their efficacy in vivo. Exhausted CAR T cells exhibit decreased proliferative capacity, impaired anti-tumor activity, and attenuated persistence. CAR T cell exhaustion has been recognized as a vital cause of nonresponse and relapse after CAR T cell therapy. However, the triggers and mechanisms leading to CAR T cell exhaustion remain blurry and complicated. Therefore, it is essential to clear the regulation network of CAR T cell exhaustion and explore potent solutions. Here, we review the diverse inducers of CAR T cell exhaustion in terms of manufacture process and immunosuppressive tumor microenvironment. In addition to the admitted immune checkpoint blockade, we also describe promising strategies that may reverse CAR T cell exhaustion including targeting the tumor microenvironment, epigenetics and transcriptomics.

Strategies for the retail platform to counteract match uncertainty: Virtual showroom and return or exchange policy

In a duopoly market consisting of a brick-and-motor (BM) store and a retailer platform, we explore strategies for the platform to counteract product match uncertainty. Three counteractive strategies are proposed: introducing virtual showrooms, offering a full-refund return policy and offering an exchange policy. Accordingly, duopoly competitive models are constructed to examine the roles of these strategies in mitigating product match uncertainty. In addition, the interaction among these three counteractive strategies is also explored. Results show that: these three strategies have positive effects on the platform’s demands but adverse effects on BM store’s. Both the full-refund return policy and the exchange policy can benefit the platform, especially the exchange policy. Nevertheless, whether introducing virtual showrooms can benefit the platform mainly relies on the establishing cost. In most cases, it is more advisable for the platform to offer an exchange policy rather than a full-refund return policy. Generally, introducing virtual showrooms and offering a return policy (an exchange policy) are two complementary methods, but the refund return policy can be seen as a replaceable measure for the exchange policy. In extensions, we explore the impacts of endogenous signal accuracy, managerial optimism and the partial-refund return policy. Several findings are also achieved: it is always beneficial to establish virtual showrooms if the platform can endogenously determine the accuracy of the information disclosed by the virtual showroom. Compared with managerial pessimism, managerial optimism generates more profits for the platform. A generous return policy leads to a higher selling price and greater profits for the platform.

Microplastics in sewage sludge destined to anaerobic digestion: The potential role of thermal pretreatment

Microplastics (MPs) are plastic particles with size smaller than 5 mm: their removal in municipal wastewater treatment plants mostly results in the accumulation of the coarser fraction into the sludge. The common application of the treated sludge as soil amendment raises the issue of the uncontrolled release of MPs into the environment, which depicts the need to identify suitable counteraction strategies. This work briefly reviews the most recent studies that focus on the fate of MPs during conventional sludge treatments, and, based on the results of this analysis, proposes the thermal pretreatment (120 °C, 30 min) of waste activated sludge (WAS) containing different kinds of MPs, in order to investigate its effect on the anaerobic biodegradability as well as on the abundance and physical features of MPs. Experimental results show that high temperatures did not alter polyethylene terephthalate (PET) MPs but the biodegradable-compostable ones (BIO-MPs), complying with the UNI EN 13432 standards. The profile of methane generation from thermally pretreated samples containing PET-MPs do not indicate any inhibition of the anaerobic process, which was positively influenced by the BIO-MPs in WAS: a 100% and 25% methane increase was observed over the control samples with and without the thermal pretreatment, respectively. Further studies are needed to better understand the mechanisms underlying biodegradable MPs behavior as well as to investigate the influence of high temperature treatments on smaller size MPs during anaerobic processes.

Twitter-based crowdsourcing: What kind of measures can help to end the COVID-19 pandemic faster?

BackgroundCrowdsourcing is a low-cost, adaptable, and innovative method to collect ideas from numerous contributors with diverse backgrounds. Crowdsourcing from social media like Twitter can be used for generating ideas in a noticeably brief time based on contributions from globally distributed users. The world has been challenged by the COVID-19 pandemic in the last several years. Measures to combat the pandemic continue to evolve worldwide, and ideas and opinions on optimal counteraction strategies are of high interest.ObjectiveThis study aimed to validate the use of Twitter as a crowdsourcing platform in order to gain an understanding of public opinion on what measures can help to end the COVID-19 pandemic faster.MethodsThis cross-sectional study was conducted during the period from December 22, 2021, to February 4, 2022. Tweets were posted by accounts operated by the authors, asking “How to faster end the COVID-19 pandemic?” and encouraging the viewers to comment on measures that they perceive would be effective to achieve this goal. The ideas from the users' comments were collected and categorized into two major themes – personal and institutional measures. In the final stage of the campaign, a Twitter poll was conducted to get additional comments and to estimate which of the two groups of measures were perceived to be important amongst Twitter users.ResultsThe crowdsourcing campaign generated seventeen suggested measures categorized into two major themes (personal and institutional) that received a total of 1,727 endorsements (supporting comments, retweets, and likes). The poll received a total of 325 votes with 58% of votes underscoring the importance of both personal and institutional measures, 20% favoring personal measures, 11% favoring institutional measures, and 11% of the votes given just out of curiosity to see the vote results.ConclusionsTwitter was utilized successfully for crowdsourcing ideas on strategies how to end the COVID-19 pandemic faster. The results indicate that the Twitter community highly values the significance of both personal responsibility and institutional measures to counteract the pandemic. This study validates the use of Twitter as a primary tool that could be used for crowdsourcing ideas with healthcare significance.

Beyond ‘Just Comes’ and ‘Know-It-Alls’: Exploring Strategies to Deal with Returnee Stigmas During Diaspora Return Visits for Knowledge Transfer

Drawing on in-depth interviews with 35 diaspora members on return visits for knowledge transfer as well as conversations with stakeholders in Ethiopia, Sierra Leone and Somaliland, this paper examines returnee stigma in the case of short-term return visits. The diaspora members in this study choose of their own volition to participate in the programme and are mostly highly educated with valued expertise in a certain field. We find that despite their skills, education and voluntariness, the returnees still experience and prepare for stigmatization in their return visits. We examine, first, the general stigmatizations that stakeholders perceive that diaspora members and returnees experience; second, diaspora members’ actual experiences of stigmatization, and third, the strategies used by diaspora members to prevent and counteract the stigmatization. The findings show that stigma towards the highly skilled diaspora members in return visits is rooted in the perceived inequalities among the home employees and communities of origin in comparison to these diaspora members, which are underpinned by global inequalities in terms of citizenship and access to international mobility. These findings contribute to the academic literature on return and returnee stigma by discussing return visits for knowledge transfer as a distinct type of return mobility, exploring returnee stigma in a context other than post-deportation and showing that diaspora returnees use preventive and counteractive strategies. Diaspora return programmes should include preparation and coaching of returnees on stigma to enhance their (re)integration and optimise their contribution to the development of the countries of origin.

Why are people antiscience, and what can we do about it?

From vaccination refusal to climate change denial, antiscience views are threatening humanity. When different individuals are provided with the same piece of scientific evidence, why do some accept whereas others dismiss it? Building on various emerging data and models that have explored the psychology of being antiscience, we specify four core bases of key principles driving antiscience attitudes. These principles are grounded in decades of research on attitudes, persuasion, social influence, social identity, and information processing. They apply across diverse domains of antiscience phenomena. Specifically, antiscience attitudes are more likely to emerge when a scientific message comes from sources perceived as lacking credibility; when the recipients embrace the social membership or identity of groups with antiscience attitudes; when the scientific message itself contradicts what recipients consider true, favorable, valuable, or moral; or when there is a mismatch between the delivery of the scientific message and the epistemic style of the recipient. Politics triggers or amplifies many principles across all four bases, making it a particularly potent force in antiscience attitudes. Guided by the key principles, we describe evidence-based counteractive strategies for increasing public acceptance of science.

Addressing the Social Loafing Problem in Assessment Practices from the Perspectives of Tanzania’s Pre-service Teachers

Recent developments of higher teacher education in Tanzania have witnessed high student enrolments necessitating change of an emphasis from individual assessment to group-based assessment practices. In this context, informed by the constructivist philosophical perspective, this article reports on the pre-service teachers’ voices regarding the prevalence, impacts and counteractive strategies of social loafing. The pre-service teachers are drawn from one higher education institution in Tanzania that serves as a case study. It draws on qualitative data collected from a sample of purposively selected undergraduate pre-service teachers. The study found social loafing tendencies to be commonplace and with far-reaching consequences amongst students as they engaged in group-based assessment tasks, hence calling for measures to redress them. Addressing social loafing in higher teacher education is crucial to avoid compromising the quality of assessment practices in the contexts of ever-rising student enrolments in many lower income countries

Advances in the study of the pathogenesis of cancer-related cognitive impairment

Advances in diagnostic and therapeutic strategies have significantly contributed to an increase in the survival rate of cancer patients. Recently, several studies suggested that cancer patients may exhibit symptoms of cognitive impairment before, during and even many years after the completion of therapies, negatively impacting the quality of life and functional independence of cancer survivors. Clinically, the coexistence of cancer and cognitive impairment reminds scientists of paraneoplastic syndrome, especially limbic encephalitis. However, some cancer patients show symptoms of cognition deterioration after treatment, without any typical psychiatric symptoms, epileptic seizures or positive antineuronal antibodies, suggesting that the relationship between cancer and cognitive deficits is more common than previously anticipated. Most importantly, many aspects of the association between cancer and cognitive impairment remain uncertain. The definitive connection between systemic cancer and central nervous system is yet to be established. Therefore, this review summarizes the current evidence on the potential pathophysiology in these patients with cancer-related cognitive impairment, and reviews the knowledge gaps and the potential counteracting strategies.

Molecular Prerequisites for Neutrophil Extracellular Trap Formation and Evasion Mechanisms of Staphylococcus aureus.

NETosis is a multi-facetted cellular process that promotes the formation of neutrophil extracellular traps (NETs). NETs as web-like structures consist of DNA fibers armed with granular proteins, histones, and microbicidal peptides, thereby exhibiting pathogen-immobilizing and antimicrobial attributes that maximize innate immune defenses against invading microbes. However, clinically relevant pathogens often tolerate entrapment and even take advantage of the remnants of NETs to cause persistent infections in mammalian hosts. Here, we briefly summarize how Staphylococcus aureus, a high-priority pathogen and causative agent of fatal diseases in humans as well as animals, catalyzes and concurrently exploits NETs during pathogenesis and recurrent infections. Specifically, we focus on toxigenic and immunomodulatory effector molecules produced by staphylococci that prime NET formation, and further highlight the molecular and underlying principles of suicidal NETosis compared to vital NET-formation by viable neutrophils in response to these stimuli. We also discuss the inflammatory potential of NET-controlled microenvironments, as excessive expulsion of NETs from activated neutrophils provokes local tissue injury and may therefore amplify staphylococcal disease severity in hospitalized or chronically ill patients. Combined with an overview of adaptation and counteracting strategies evolved by S. aureus to impede NET-mediated killing, these insights may stimulate biomedical research activities to uncover novel aspects of NET biology at the host-microbe interface.