Less-Lethal Weapons, including electric Tasers, velocity-reduction bullet-capture projectiles, rubber bullets, beanbag rounds, and other less-lethal projectiles used in police departments, federal and local law enforcement agencies, and military policing operations, as well as for private use, are topics of significant debate in recent years. These weapons can reduce collateral damage, reputational risk, and legal exposure while preventing wrongful and unnecessary deaths caused by conventional bullet wounds. Yet, opponents have highlighted concerns regarding the safety and effectiveness of these weapons, as well as their potential to cause injury or even death. While the primary duty of law enforcement officials is to preserve order and execute the law while protecting individual rights, they ultimately achieve these goals by exercising their coercive authority. Society expects police officers to rely on their professional training and judgment when using physical force to defend citizens and themselves or to apprehend criminal suspects. Because police officers must occasionally participate in physical acts of coercion, it is unavoidable that some of these interactions may result in bodily injuries to individuals, including the officers themselves. These injuries have real costs, such as medical treatment, lost wages, municipal liability, court claims and settlements, riots, and legal or even criminal exposure, as well as less-tangible collateral costs, such as the erosion of police legitimacy and public trust, which are more difficult to quantify but arguably more influential in shaping long-term public perceptions than personal injuries alone. Less lethal technology eliminates some of the concerns raised by lethal weaponry. This study reviews the advantages and disadvantages of these less-lethal weapon technologies versus traditional firearms for use by the police force, federal agencies, and military police while also performing advanced analytics to model the valuation and return on investment for a law enforcement organization implementing such technologies.

Cancer, a pervasive threat to human health, presents formidable challenges to traditional treatment approaches. Tumor immunotherapy has emerged as a promising strategy for combating malignancies by bolstering the body's immune response to thwart tumor metastasis and recurrence. Nonetheless, the intricacies of tumors, patient heterogeneity, and the presence of tumor-immunosuppressive microenvironments have limited the overall efficacy of immunotherapy, achieving only approximately a 20% success rate. In recent years, nanomaterials have garnered increasing attention in the realm of tumor immunotherapy due to their inherent advantages, such as excellent biocompatibility, precise targeting, and controlled drug release. Nanomaterials empower immunostimulatory molecules and therapeutic agents with the ability to specifically target tumors, amplify drug accumulation at tumor sites, facilitate local immune modulation, alleviate immunosuppressive microenvironments, and thereby enhance the effectiveness of tumor immunotherapy. This review provides an overview of the current state of immunotherapy and offers insights into the ongoing research progress surrounding various nanomaterials aimed at augmenting the efficacy of immunotherapy.

This research evaluates the efficacy of survival models in forecasting startup failures and investigates their economic implications. Several machine learning survival models, including Kernel SVM, DeepSurv, Survival Random Forest, and MTLR, are assessed using the concordance index (C-index) as a measure of prediction accuracy. The findings reveal that more sophisticated models, such as Multi-Task Logical Regression (MTLR) and Random Forest, outperform the standard Cox and Kaplan Meier (K-M) models in terms of predicted accuracy.

The paramount prerequisite for effective anti-cancer drugs is their ability to eradicate malignant cells while sparing non-cancer cells. The divergence in properties between malignant and non-cancer cells establishes a "therapeutic window," a critical consideration for achieving desirable treatment outcomes. Central to this is the imperative of a cancer drug's "selectivity and specificity." Taxanes, a pivotal class of successful anti-cancer drugs, continue to serve as the linchpin of cancer treatment due to their efficacy across a spectrum of cancer types. Operating as broad-spectrum chemotherapeutic agents, taxanes exert cytotoxic effects on proliferative cancer cells by binding to and stabilizing microtubules, disrupting mitosis, inducing mitotic catastrophe, and resulting in cell death. The distinct proliferative nature of cancer cells, as opposed to less proliferative non-cancer cells, affords taxanes a measure of specificity and selectivity. Nevertheless, sporadic yet recurring evidence suggests that taxanes also operate through non-mitotic mechanisms. Taxanes' binding and stabilization of microtubules lead to micronucleation and subsequent cell death, impacting both mitotic and non-mitotic cells. Recent discoveries indicate that the flexible and weakened nuclear envelope of malignant cells renders them sensitive to taxane-mediated micronucleation and cell death during various phases of the cell cycle. Conversely, non-cancerous cells typically exhibit a more robust and sturdy nuclear envelope, rendering them more tolerant to taxane-induced nuclear envelope fragmentation and subsequent micronucleation and cell death. The expression levels of nuclear envelope structural proteins, particularly Lamin A/C, emerge as indicators of taxane sensitivity. This evolving understanding underscores that nuclear envelope malleability, in conjunction with a high proliferation rate, is a pivotal determinant of taxane specificity and selectivity against malignant cells. These insights necessitate reconsidering oncological strategies to augment taxane efficacy, overcome resistance, and mitigate side effects.

This study investigates the likelihood of time to bank failures in the US between 2001 and April 2023, based on data collected from the Federal Deposit Insurance Corporation's report on "Bank Failures in Brief - Summary 2001 through 2023". The dataset includes 564 instances of bank failures and several variables that may be related to the likelihood of such events, such as asset amount, deposit amount, ADR, deposit level, asset level, inflation rate, short-term interest rates, bank reserves, and GDP growth rate. We explore the efficacy of machine learning survival models in predicting bank failures and compare the performance of different models. Our findings shed light on the factors that may influence the probability of bank failures with a time perspective and provide insights for improving risk management practices in the banking industry.

Cancer treatment faces multiple challenges, including tumor heterogeneity, drug resistance, microenvironment influence, treatment side effects, and treatment cost. The heterogeneity of the tumor makes the effect of the same treatment vary in different patients, so the development of personalized treatment strategies is crucial. In addition, resistance of tumor cells to therapeutic drugs is a major challenge, and new strategies to overcome resistance are needed. As a cutting-edge field of science and technology, nanotechnology has brought great potential and opportunities for tumor treatment. Nanoparticle drug delivery systems improve drug efficacy and reduce side effects through precise targeted delivery and controlled release. Cell-membrane coated nanoparticles show great promise in tumor therapy. Nanoparticles coated with cell membranes have good biocompatibility, can reduce the obstacles of immune rejection and cell uptake, improve the accumulation and retention of drugs in tumor tissues, and have good drug delivery ability, drug stability and control release ability. This review discusses advances in the use of cell-membrane coated nanoparticles to target tumor drugs.

This study employs empirical analysis using an econometric model that examines the interdependence among environmental degradation, exports, and economic development with energy use. It also provides an environmental Kuznets curve (EKC) for selected South Asian economies utilizing time-series data. The findings reveal a long-term, stable equilibrium link between energy demand and pollution. There exists a positive relationship between structural factors and pollution. Moreover, this study constructs a model of exports and pollution from an interdependent perspective. The three perspectives are tested: the scale and structure of energy consumption considering the twin constraints of export-trade and pollution, and the scale of pollution in export-trade constraint. These results show that the increase in energy use leads to higher CO2 emissions amidst export volume. However, in the presence of income, the scale of effect lowers a little. The analysis also supports the presence of Kuznets curve for south-Asian economies. The results imply substantial scope for development in the energy use and pollution structure within South Asia's current export trade process. This development can be attained by regulating energy use and enhancing system efficacy without necessitating changes to the scale effect or structural effect.

Nanomaterials have shown great potential in anti-tumor applications and are currently the focus of research. This review article aims to provide a comprehensive overview of the challenges encountered in oncology treatment and how nanomaterials are being utilized to overcome these obstacles. The authors discuss the limitations of conventional treatments, including limited efficacy, side effects, and toxicity issues. They highlight the importance of early tumour diagnosis and personalized treatment plans, as well as the need for innovative therapeutic approaches such as targeted therapy, immunotherapy, and gene therapy. The article primarily focuses on how nanomaterials can be engineered to achieve specific recognition and aggregation within tumour tissues through surface modifications involving targeting molecules such as antibodies, peptides, and receptor ligands. This surface modification technique facilitates improved targeting in the targeting of photodynamic therapy, while minimizing harm to normal tissues. The authors also discuss the potential and future prospects of nanomaterials in tumour therapy, including breakthroughs in their application, biosafety concerns, biocompatibility issues, preparation processes, clinical translation challenges, interdisciplinary cooperation, international exchange, relevant regulations and ethical guidelines. Overall, this review highlights the substantial potential of nanomaterials in oncology treatment, emphasizing the need for careful consideration of safety concerns to ensure their safe and effective application. The authors conclude that strengthening interdisciplinary cooperation and international exchange will contribute to the healthy development of nanomaterials in oncology treatment.

Cancer, a global health menace, continues to pose significant challenges in terms of incidence and mortality, necessitating innovative therapeutic strategies. Despite existing treatments, the limitations persist, prompting a quest for novel approaches. The emergence of immunotherapy marked a transformative era in solid tumor treatments, yet its efficacy is constrained by adverse effects. Concurrently, the integration of advanced technologies into cancer treatment explores the vast potential residing at the molecular level through gene analysis and manipulation. This review articulates the role of state-of-the-art genome editing technology, notably clustered regularly interspaced short palindromic repeats (CRISPR-Cas9), in overcoming the constraints of immunotherapy for cancers. Unveiling the intricacies of CRISPR-Cas9-mediated genome editing, the review introduces the formidable CRISPR toolbox. A spotlight is cast on the transformative impact of CRISPR-induced double-strand breaks (DSBs) on cancer immunotherapy, encompassing knockout and knock-in strategies. The utilization of CRISPR/Cas9 technology in pre-clinical cancer research has demonstrated notable success; however, its transition to the clinical setting remains in the nascent stages of development. This review aims to elucidate the fundamental aspects of CRISPR technology and offer a comprehensive survey of its existing applications while outlining its prospective role in the realm of cancer therapies. Through an exploration of CRISPR's mechanisms, current applications, and anticipated future potentials, this review provides valuable insights into the evolving landscape of CRISPR-based cancer treatment strategies.

The enactment of policies that bolster new research and development (R&D) institutions stands as a pivotal strategy to catalyze urban innovation and development. Adopting a strategic lens of innovation chain management and employing the Differences-in-Differences (DID) method to scrutinize panel data from 43 Chinese cities spanning 2008 to 2019, this study probes the efficacy and underlying mechanisms of policies designed to support nascent R&D institutions in facilitating urban innovation. Empirical findings reveal that policies in support of new R&D institutions have markedly enhanced the three integral stages of the urban innovation chain: research and development, transfer, and application. Furthermore, the innovation ambiance within cities and the innovative activities of enterprises emerge as significant mediators between support policies and the output of urban innovation across these stages. A regional heterogeneity analysis unveils that the impact of support policies on the output of urban innovation diverges across regions, with a notably more pronounced effect observed in the eastern region compared to central and western regions. An objective appraisal of the policy's impact on urban innovation not only aids in delving into the profound implementation effects of policy instruments but also furnishes policy-makers with decision-making references for optimizing the utilization of support policies for new R&D institutions to advance the edification of the national innovation system.

The requirement of having multiple nanocarriers (NCs) and active agents for improved therapy, imaging, and controlled release of medications efficiently in one platform has made the creation of therapeutics and theragnostic nanodrug delivery systems a difficult task for present researchers. Multiple drug resistance (MDR), a high clearance rate, severe side effects, undesirable drug distribution to the specific site of liver cancer, and a low concentration of medication that reaches liver cancer cells are just a few of the drawbacks of traditional liver cancer chemotherapy. As a result, new techniques and NCs must be developed to transport the medication molecules targeted to the malignant hepatocytes in an acceptable number and duration inside the therapeutic window. Because of the great efficacy of drug loading or drug encapsulation efficiency, high cellular uptake, high drug release, and minimal adverse effects, therapeutics and theragnostic systems have benefits over conventional chemotherapy. These NCs have a high drug accumulation rate in tumours while causing minimal toxicity in healthy tissues. This study focuses on current research on NC-based therapies and theragnostic drug delivery systems, omitting nanotechnology's negative consequences in the field of drug delivery systems. Clinical advancements of theragnostic NCs for liver cancer, on the other hand, are not covered in this article. Only the most current breakthroughs in NC-based drug delivery systems for liver cancer therapy and diagnosis are discussed in this study. This review will not go over the detrimental effects of individual NCs in the medication delivery system.

Approximately 28 million individuals in the United States face the risk of developing precancerous colonic adenomas (polyps) and potentially progressing to colorectal cancer (CRC). While a promising strategy for CRC prevention involves pharmacological intervention, such as cancer chemoprevention or interception, currently, there are no FDA-approved drugs capable of preventing the formation or progression of adenomas to adenocarcinoma. Numerous clinical, epidemiological, and preclinical studies have offered compelling evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention. However, the prolonged use of NSAIDs is not FDA-approved due to potential life-threatening toxicities resulting from cyclooxygenase (COX) inhibition and the depletion of physiological prostaglandins. Despite indications that the COX inhibitory activity of NSAIDs may not be essential for their antineoplastic effects, the absence of a well-defined target impeded the development of derivatives that do not inhibit COX. Earlier research suggests that the inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) may be responsible, at least in part, for the antineoplastic activity of the NSAID sulindac. This could potentially offer a novel target for CRC chemoprevention. To identify the cGMP PDE isozyme(s) contributing to the antineoplastic activity of sulindac, we synthesized a chemically diverse library of over 1500 compounds, all sharing the indene scaffold of sulindac. Subsequently, we screened these compounds for their impact on cancer cell growth and PDE inhibitory activity. From this screening, a series of lead compounds emerged. These compounds lacked COX-1 and COX-2 inhibitory activity, surpassing sulindac in potency to inhibit CRC cell growth. Importantly, they demonstrated greater selectivity by not affecting normal cell growth. Through chemical optimization, we identified several development candidates that selectively inhibit PDE5 and/or PDE10. These compounds activate cGMP/PKG signaling, suppressing Wnt/β-catenin transcription. This action counters the growth advantages resulting from APC or CTNNB1 mutations, which are responsible for most human CRCs. This review delves into the scientific literature supporting PDE5 and/or PDE10 as potential targets for CRC chemoprevention or interception. Our findings suggest a promising avenue for developing drugs that may effectively intervene in the progression of colorectal cancer, offering hope for improved preventive strategies in the future.