Multiple Agents Research Articles

The Emerging Potential of Apolipoprotein C-III Inhibition for ASCVD Prevention: A State-of-the-Art Review.

Multiple agents are being developed that inhibit apolipoprotein (apo) C-III. This state-of-the-art review examines their potential for atherosclerotic cardiovascular disease (ASCVD) risk reduction. Apo C-III, an apolipoprotein on the surface of triglyceride-rich lipoproteins (TRLs), impairs clearance of TRLs through both lipoprotein lipase dependent and independent pathways, thereby resulting in increased concentrations of triglycerides. Apo C-III has also been shown to have pro-atherogenic effects when bound to high-density lipoprotein (HDL) particles. Classical and genetic epidemiology studies provide support for the concept that apo C-III is associated with an increased risk of ASCVD events. Drug efficacy of agents that silence APOC3 mRNA has been studied in populations with varying hypertriglyceridemia severity, including those with familial chylomicronemia syndrome, multifactorial chylomicronemia syndrome/severe hypertriglyceridemia, and mixed hyperlipidemia. Randomized controlled trials have reported significant reductions in TG and non-HDL cholesterol levels among these patients treated with APOC3 inhibitors. Upcoming clinical outcomes trials seek to establish a role for APOC3 inhibitors to reduce risk of ASCVD.

Prospect of emerging treatments for HBV functional cure.

Functional cure, defined as sustained hepatitis B surface antigen (HBsAg) seroclearance with unquantifiable hepatitis B virus (HBV) DNA at 24 weeks off treatment, is a favorable treatment endpoint in chronic hepatitis B (CHB). Nonetheless, functional cure is rarely attained with the current treatment modalities of nucleos(t)ide analogues (NUCs) and pegylated interferon alpha (Peg-IFNα). Multiple novel virus-targeting agents and immunomodulators are under development for HBV with functional cure as the treatment goal. Among virus-targeting agents, antisense oligonucleotides (ASOs) and small-interfering RNA (siRNAs) are the most advanced in the developmental pipeline, and can induce potent and sustainable HBsAg suppression. The other virus-targeting agents have varying effects on HBsAg and HBV DNA, depending on the drug mechanism. In contrast, immunomodulators have modest effects on HBsAg and have limited roles in monotherapy. Multiple combination regimens incorporating RNA interference agents with immunomodulators have been studied through many ongoing clinical trials. These combination strategies demonstrate synergistic effects in inducing functional cure, and will likely be the future direction of development. Despite the promising results, research is warranted to optimize treatment protocols and to establish criteria for NUC withdrawal after novel therapies. Functional cure is now an attainable target in CHB, and the emerging novel therapeutics will revolutionize CHB management.

A Social Group Chatbot System by Multiple Topics Tracking and Atkinson‐Shiffrin Memory Model Using AI Agents Collaboration

ABSTRACTThe widespread use of Internet has accelerated the explosive growth of data, which in turn leads to information overload and information confusion. This makes it difficult for us to communicate effectively in social groups, thereby intensifying the demands for emotional companionship. Therefore, we propose a novel social group chatting framework based on Large Language Model (LLM) powered multiple autonomous agents collaboration in this article. Specifically, BERTopic is used to extract topics from history chatting content for each social group everyday, and then multiple topics tracking is realised through multi‐level association by adaptive time sliding‐window mechanism and optimal matching. Furthermore, we use topic tracking architecture and prompts to design and implement an AI Chatbot system with different characters that can conduct natural language conversations with users in online social group. LLM, as the controller and coordinator of the whole AI Chatbot for sub‐tasks, allows different AI Agents to autonomously decide whether to participate in current topic, how to generate response, and whether to propose a new topic. Each AI Agent has their own multi‐store memory system based on the Atkinson‐Shiffrin model. Finally, we construct a verification environment based on online game that is consistent with real society. Subjective and objective evaluation methods were deployed to perform qualitative and quantitative analyses to demonstrate the performance of our AI Chatbot system.

Pioneering Innovations in Biological Weed Control: A Comprehensive Review

The biological method of weed control is an effective option. Before implementing bio-agents, there is a need for a better understanding of the mechanisms involved in interactions by multiple agents against weeds. This covers knowledge of how plants integrate and prioritize their responses to multiple attackers. Across the globe, terrestrial ecosystems are known to be characterized by a huge diversity of species and a corresponding diversity of interactions between these species. These include species of different trophic levels of habitats on the same food chain. Plants undoubtedly play significant role as intermediaries in interactions between the insect and microbial populations with which they are involved. Plant interactions brought forth by one species can have cascading impacts on other species, influencing their abundances and the composition of communities. Several research efforts are underway to develop highly effective biological control agents to reliably control a problematic broad spectrum of weeds. Sustainable and ecosystem-compatible weed management for controlling weeds by biological means, such as insects, bio-agents, myco-herbicides and harmful Rhizobacteria. Their interaction with cultural practices and allelochemicals are some biological components of sustainable agriculture. Hence, biological agents enhance efficiency and restrict the detrimental effect of weeds compared to weeds being left alone. The challenge is to identify appropriate microbe/bioagents, which reduce weed growth. Logically, biological weed management is the only way to control weeds in eco-friendly weed management.

Research on adaptive circuit structure optimization in electronic design based on Asynchronous Advantage Actor Critic (A3C) algorithm

The circuit structure optimizationed with the traditional method is often difficult to meet the complex and changeable design requirements. In this paper the A3C algorithm has been applied to integrate strategy learning and value learning for the circuit structure optimization. This integration can facilitate continuous interaction with the environment, enabling automatic adjustment of circuit structures to meet the complex design requirements. Gain, bandwidth, latency, and power consumption have been set as the optimization objectives, and the actions of the intelligent agent, which include adding, deleting, modifying connection lines, and adjusting component parameters have been introduced in detail. Once the Actor and Critic networks have been established, multiple agents can operate concurrently, translating optimization objectives into reward signals and providing direction and motivation for agent learning. Then with the proposed method, the circuit structure of one switch audio power amplifier has been designed in a simulation environment. The structure optimization results demonstrated that the gain can reach 78.4 dB at convergence of the A3C algorithm, while the bandwidth can reach 156.2 MHz at convergence, and both the circuit delay and power consumption have been reduced significantly. Obviously, the application of the A3C algorithm can effectively optimize the circuit structures through offering more flexible and efficient solutions.

Targeting Endogenous Tau in Seeded Tauopathy Models Inhibits Tau Spread.

The transmission of tau pathology has been proposed as one of the major mechanisms for the spatiotemporal spreading of tau pathology in neurodegenerative diseases. Over the last decade, studies have demonstrated that targeting total or pathological tau using tau antibodies can mitigate the development of tau pathology in tauopathy or Alzheimer's disease (AD) mouse models, and multiple tau immunotherapy agents have progressed to clinical trials. Tau antibodies are believed to inhibit the internalization of pathologic seeds and/or block seed elongation after seed internalization. To further address the mechanism of tau antibody inhibition of pathological spread, we conducted immunotherapy studies in mouse primary neurons and wild-type mice (females) seeded with AD patient-derived tau to induce the formation and spreading of tau pathology. Notably, we evaluated the effect of a mouse tau-specific antibody (mTau8) which does not interact with AD-tau seeds in these models. Our results show that mTau8 crosses the blood-brain barrier at levels similar to other antibodies and effectively decreases AD-tau-seeded tau pathology in vitro and in vivo. Importantly, our data suggest that mTau8 binds to endogenous intraneuronal mouse tau, thereby inhibiting the elongation of internalized tau seeds. These findings provide valuable insights into the possible mechanism underlying antibody-based therapies for treating tauopathies.Significance Statement The transmission of tau pathology plays key role in the pathoclinical progression of tauopathy. Studies have shown that tau antibody treatment can mitigate tau pathology in transgenic and spreading models of tauopathy. To explore the mechanisms involved in this procedure, we conducted immunotherapy studies on human tau seeds induced tau spreading models using a mouse tau-specific antibody (mTau8), which does not interact with human-tau seeds. Our findings in the study enhance our understanding of antibody-based therapies for tauopathies.

Benefits of combining SGLT2 inhibitors and pioglitazone on risk of MASH in type 2 diabetes-A real-world study.

Both pioglitazone and glucagon-like peptide 1 receptor agonists (GLP1RA) alone improve metabolic dysfunction-associated steatohepatitis (MASH) in randomized clinical trials, whereas preclinical studies suggested MASH benefits with sodium glucose co-transporter 2 inhibitors (SGLT2i). In the real world, patients with type 2 diabetes often require multiple agents for glycaemic control. Here, we investigated the benefits of combining these agents on risks of MASH. Longitudinal changes in FibroScan-aspartate aminotransferase (FAST) score were measured in 888 patients with type 2 diabetes. Use of pioglitazone, GLP1RA and/or SGLT2i was defined as continuous prescriptions of ≥180 days prior to their last reassessment FibroScan. Multivariable logistic regression analysis was conducted to evaluate the associations between use of these agents and FAST score changes. Over a median follow-up of 3.9 years, the increasing number of these agents used was significantly associated with more reductions in FAST score (p for trend <0.01). Dual combination was independently associated with a higher likelihood of achieving low FAST score at reassessment than single use of any of these agents (odds ratio [OR] 2.84, p = 0.01). Among the different drug combinations, using SGLT2i and pioglitazone (median dose 15 mg daily) together, as compared to not using any of these three agents, was associated with a higher likelihood of both low FAST score at reassessment (OR 6.51, p = 0.008) and FAST score regression (OR 12.52, p = 0.009), after adjusting for changes in glycaemic control and body weight during the study. Combining SGLT2i and pioglitazone is a potentially useful strategy to ameliorate 'at-risk' MASH in patients with type 2 diabetes.

The Role of Multiple Mediation with Contextual Neighborhood Measures in Ovarian Cancer Survival..

BackgroundMediation by multiple agents can affect the relation between neighborhood deprivation and segregation indices and ovarian cancer survival. In this paper, we examine a variety of potential clinical mediators in the association between deprivation indices (DIs) and segregation indices (SIs) with all-cause survival among women with ovarian cancer in the African American Cancer Epidemiology Study (AACES). MethodsWe use novel Bayesian multiple mediation structural models to assess the joint role of mediators (stage at diagnosis, histology, diagnostic delay) combined with the DIs and SIs (Yost, ADI, Kolak’s URB, ICE-income) and a set of confounders with survival. The confounder set is selected in a preliminary step, and each DI or SI is included in separate model fits. ResultsWhen multiple mediators are included, the total impact of DIs and SIs on survival is much reduced. Unlike the single mediator examples previously reported, the Yost, ADI and ICE-income indices do not display significant direct effects. This suggests that when important clinical mediators are included, the impact of neighborhood SES indices is significantly attenuated. It is also clear that certain behavioral and demographic measures such as physical activity, smoking, or adjusted family income do not have a significant role in survival when mediated by clinical factors. ConclusionMultiple mediation via clinical and diagnostic-related measures reduces the contextual effects of neighborhood measures on ovarian cancer survival. The robust association of the Kolak URB index on survival may be due to its relevance to access to care, unlike SES-based indices whose impact was significantly reduced when important clinical mediators were included.

Multi-scale investigation on water stability and anti-aging performance of granite asphalt mixture modified with composite anti-stripping agents

This study aims to improve the water damage resistance of granite asphalt mixtures. Five types of composite modified asphalt were developed using organic anti-stripping agents AMRIII, LQ-2020, ultrafine hydrated lime (HL), and SBS modified asphalt, and the effects of aging on the mechanical properties of these modified asphalt mixtures were evaluated. Fourier Transform Infrared Spectroscopy (FTIR), pull-off tests, and indirect tensile strength tests were the primary analytical methods used. The results indicated that the anti-stripping agents physically mixed with the SBS modified asphalt without any chemical reaction. The SBS modified asphalt containing anti-stripping agents exhibited better mechanical strength compared to unmodified SBS asphalt, with the combined use of multiple anti-stripping agents proving more effective than individual applications. At five freeze-thaw conditions without aging, the enhancement ratios of indirect tensile strength test results of single addition of AMRIII, LQ-2020, HL and combined addition of AMRIII/HL and LQ-2020/HL were 27.27%, 36.36%, 14.29%, 50.91% and 46.41%, respectively. The addition of the anti-stripping agent enhanced the cohesive and adhesive energy. Aging reduced the water stability of the mixtures. Different modified asphalts have various sensitivity to aging, with the combination of AMRIII and HL showing the best aging resistance performance. Additionally, it was found that surface free energy had a strong correlation with water damage indicators, suggesting its potential for verifying the water stability of asphalt mixtures.

OA23 A complex case of psoriatic juvenile idiopathic arthritis

Abstract Introduction This patient demonstrates many of the challenges that can be faced when treating juvenile idiopathic arthritis (JIA). The combination of difficult to treat disease, together with her social situation has made her case a particularly challenging one. Her case outlines the necessity of a multidisciplinary, and multi-agency, approach to treatment to ensure patient’s needs are met. Case description This patient presented at five years old with a several year history of swelling in her knees and feet. On examination she had a polyarthritis affecting bilateral metacarpal-phalangeal joints, both wrists, both elbows, and both knees. She is ANA negative and RF negative. She was initially treated with intravenous methylprednisolone (IVMP), methotrexate and joint injections. This patient’s disease has been very difficult to treat, with inadequate response to multiple medications (see table 1). She has had multiple flares, required 12 General anaesthetics for joint injections, as well as several pulses of IVMP to help control her inflammation. The patient has persistent effusion of her knees, not responsive to intra-articular steroids and the presence of significant crepitus. An MRI of her right knee showed 14 mm loose bony fragment, in addition to synovitis and effusion. The orthopaedic team were not keen to manage this surgically. She was discussed with other centres, following which combination of biologics / biologic with small molecule (JAK inhibitors) was felt to be the next option. Adalimumab was added to Tofacitinib in June 2024 due to inadequate control. Discussion The difficulty in treating this patient have made us consider alternative diagnosis. MRI scans of her hips done in April 2023 showed bilateral coxa vara. This, along with no evidence of erosions and poor response to treatment, raised the possibility of Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome. However, she did not have camptodactyly, her echocardiogram did not show pericardial effusion and the genetic testing was negative. This patient has a complex social background. She lives with her mother, and no longer has contact with her father, or his side of the family. Her mother was involved in a car accident many years ago and due to a traumatic brain injury has difficulty with memory. Her mother has also suffered with depression. This, together with financial difficulties, have led to many missed appointments and concerns around compliance, despite continuous support from our specialist nursing team. The patient has poor school attendance- more than can be accounted for by her disease. Her current school are very supportive. They give reminders about appointments, and a teacher collects her from home and takes her to school each day. When she starts secondary school this level of support will not be available. Providing psychological support has been challenging due to her age and available resources. However, now she is 11 years old she will be able to get involved with our youth team. She struggles with needle phobia, and is very self-conscious about her swollen knees, and the sound they make when she moves. At various times, safeguarding referrals have been made to try to support the family, none of which were accepted. Her mother’s reluctance to accept support from social services did not help either. This has presented the team with many challenges. Key learning points • This is a challenging case of psoriatic JIA, unresponsive to multiple biologic agents, complicated by difficult social situation influencing care decisions. Non-attendance to clinics has contributed to delay in escalation of treatment at times. She was discussed at various regional and national MDT meetings, both in terms of diagnosis and management plans. Other differential diagnoses were considered and ruled out. • The importance of addressing all the biopsychosocial aspects of care are highlighted in this case. The difficulty of balancing ongoing rapport and trust with the family, and ensuring safeguarding for the patient has been challenging. Learning points: • Importance of multi-agency and multi-centre working in management of patients with complicated JIA. • Importance of difficult social situation affecting timely management decisions and the role of family support in optimising medical care. • Even with newer treatments being approved on regular basis for JIA, it is important to recognise there are patients who prove resistant to many of these and more evidence is needed for combining biologics in such patients.

Multi-agent reinforcement learning with synchronized and decomposed reward automaton synthesized from reactive temporal logic

Multi-agent systems (MAS) consist of multiple autonomous agents interacting to achieve collective objectives. Multi-agent reinforcement learning (MARL) enhances these systems by enabling agents to learn optimal behaviors through interaction, thus improving their coordination in dynamic environments. However, MARL faces significant challenges in adapting to complex dependencies on past states and actions, which are not adequately represented by the current state alone in reactive systems. This paper addresses these challenges by considering MAS operating under task specifications formulated as Generalized Reactivity of rank 1 (GR(1)). These synthesized strategies are used as a priori knowledge to guide the learning. To tackle the difficulties of handling non-Markovian tasks in reactive systems, we propose a novel synchronized decentralized training paradigm that guides agents to learn within the MARL framework using a reward structure constructed from decomposed synthesized strategies of GR(1). We initially formalize the synthesis of GR(1) strategies as a reachability problem of winning states of the system. Subsequently, we develop a decomposition mechanism that constructs individual reward structures for decentralized MARL, incorporating potential values calculated through value iteration. Theoretical proofs are provided to verify that the safety and liveness properties are preserved. We evaluate our approach against other state-of-the-art methods under various GR(1) specifications and scenario maps, demonstrating superior learning efficacy and optimal rewards per episode. Additionally, we show that the decentralized training paradigm outperforms the centralized training paradigm. The value iteration strategy used to calculate potential values for the reward structure is compared against two other strategies, showcasing its advantages.

Acquired factor V inhibitor treated with rituximab

Acquired factor V (FV) inhibitors are extremely rare and present with a broad spectrum ranging from asymptomatic laboratory anomalies to life-threatening critical bleeds. The overall rarity along with the heterogeneity of clinical presentations poses a challenge in diagnosis. There is currently no standard of care immunosuppressive therapy (IST) in these settings. Most patients in the literature receive multiple agents, including but not limited to combinations of IST and/or recombinant products.Here, we present a case of a man in his 50s who initially presented with oozing at peripheral IV and tracheostomy sites with intermittent epistaxis. He was later found to have an FV activity level of less than 1% and an FV inhibitor titre of 184 Bethesda units/mL. The patient was initially stabilised with fresh frozen plasma, platelets and tranexamic acid and treated with intravenous immunoglobulin and glucocorticoids. However, this resulted in only mild improvement in his coagulation studies. He was then treated with weekly doses of rituximab for 4 weeks with ongoing glucocorticoids without complications. This adds to the growing literature on rituximab as a possible treatment option for acquired FV inhibitors.

The fluency-based semantic network of LLMs differs from humans

Modern Large Language Models (LLMs) exhibit complexity and granularity similar to humans in the field of natural language processing, challenging the boundaries between humans and machines in language understanding and creativity. However, whether the semantic network of LLMs is similar to humans is still unclear. We examined the representative closed-source LLMs, GPT-3.5-Turbo and GPT-4, with open-source LLMs, LLaMA-2-70B, LLaMA-3-8B, LLaMA-3-70B using semantic fluency tasks widely used to study the structure of semantic networks in humans. To enhance the comparability of semantic networks between humans and LLMs, we innovatively employed role-playing to generate multiple agents, which is equivalent to recruiting multiple LLM participants. The results indicate that the semantic network of LLMs has poorer interconnectivity, local association organization, and flexibility compared to humans, which suggests that LLMs have lower search efficiency and more rigid thinking in the semantic space and may further affect their performance in creative writing and reasoning.

From the INVICTUS Trial to Current Considerations: It’s Not Time to Retire Vitamin K Inhibitors Yet!

Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and oral anticoagulation is the cornerstone of stroke prevention in AF. Direct oral anticoagulants (DOAC) significantly reduce the incidence of intracerebral hemorrhage with preserved efficacy for preventing stroke compared to vitamin K antagonists (VKA). However, the pivotal randomized controlled trials (RCTs) of DOAC excluded patients with valvular heart disease, especially mitral stenosis, which remains an exclusion criterion for DOAC use. The INVICTUS study was a large multicenter global RCT aimed at evaluating the role of DOAC compared to VKA in stroke prevention among patients with rheumatic valvular AF. In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death. Unfortunately, the bleeding rates were not lower with rivaroxaban either. The death and drug discontinuation rates were higher in the DOAC arm. Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility. Hence, for AF complicating moderate-to-severe mitral stenosis or prosthetic valve VKA remains the standard of care. However, DOAC can be used in patients with surgical bioprosthetic valve implantation, TAVR, and other native valve diseases with AF, except for moderate-to-severe mitral stenosis. Factor XI inhibitors represent a breakthrough in anticoagulation as they aim to dissociate thrombosis from hemostasis, thereby indicating a potential to cut down bleeding further. Multiple agents (monoclonal antibodies—e.g., osocimab, anti-sense oligonucleotides—e.g., fesomersen, and small molecule inhibitors—e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease.

Potential Strategies for Overcoming Drug Resistance Pathways Using Propolis and Its Polyphenolic/Flavonoid Compounds in Combination with Chemotherapy and Radiotherapy.

Conventional cancer treatments include surgical resection, chemotherapy, hyperthermia, immunotherapy, hormone therapy, and locally targeted therapies such as radiation therapy. Standard cancer therapies often require the use of multiple agents, which can activate nuclear factor kappa B (NF-κB) in tumor cells, leading to reduced cell death and increased drug resistance. Moreover, the use of multiple agents also contributes to added toxicity, resulting in poor treatment outcomes. Cancer cells gradually develop resistance to almost all chemotherapeutics through various mechanisms, such as drug efflux, alterations in drug metabolism and transport, changes in signal transduction pathways, enhanced DNA repair capacity, evasion of apoptosis, increased mutations, reactivation of drug targets, interaction with the cancer microenvironment, cancer cell-stroma interactions, epithelial-mesenchymal transition (EMT)-mediated chemoresistance, epigenetic modifications, metabolic alterations, and the effect of cancer stem cells (CSCs). Developing new strategies to improve chemotherapy sensitivity while minimizing side effects is essential for achieving better therapeutic outcomes and enhancing patients' quality of life. One promising approach involves combining conventional cancer treatments with propolis and its flavonoids. These natural compounds may enhance tumor response to treatment while reducing toxicity. Propolis and its components can sensitize cancer cells to chemotherapeutic agents, likely by inhibiting NF-κB activation, reprogramming tumor-associated macrophages (TAMs; an M2-like phenotype), and thereby reducing the release of matrix metalloproteinase (MMP)-9, cytokines, chemokines, and the vascular endothelial growth factor (VEGF). By reducing TAMs, propolis and its components may also overcome EMT-mediated chemoresistance, disrupt the crosstalk between macrophages and CSCs, inhibit the maintenance of stemness, and reverse acquired immunosuppression, thus promoting an antitumor response mediated by cytotoxic T-cells. This review highlights the potential of flavonoids to modulate the responsiveness of cancer to conventional treatment modalities. The evidence suggests that novel therapeutic strategies incorporating flavonoids could be developed to improve treatment outcomes. The positive effects of combining propolis with chemotherapeutics include reduced cytotoxicity to peripheral blood leukocytes, liver, and kidney cells. Therefore, polyphenolic/flavonoid components may hold potential for use in combination with chemotherapeutic agents in the clinical treatment of various types of cancers.

Virulence genes and antibiotic susceptibility patterns of Escherichia coli isolated from nosocomial urinary tract infections in the northwest of Iran during 2022-2023: A cross-sectional study.

Urinary tract infections (UTIs) are prevalent among hospitalized patients, constituting the most frequent health-care infections. Uropathogenic Escherichia coli (UPEC) is leading causative agent of UTIs. The present study was aimed to examine the susceptibility of UPEC isolates obtained from nosocomial cases to antibiotics, as well as their biofilm formation capability and frequency of virulence genes. A total of 100 UPEC isolates were collected from nosocomial UTIs at Imam Reza Hospitals in Tabriz, Iran, spanning from April 2022 to January 2023. The antimicrobial susceptibility patterns were evaluated using the disk diffusion method, along with the detection of broad-spectrum β-lactam enzymes (ESBLs) and carbapenemases. The ability of isolates to form biofilms was assessed using the microtiter-plate method, while the PCR method was employed to identify the presence of virulence genes. The highest resistance was observed toward piperacillin (82%), followed by aztreonam and ciprofloxacin (81%), while the lowest resistance was found against piperacillin/tazobactam (12%) and meropenem (9%). ESBLs were detected in 62% of the isolates. The microtiter-plate results revealed strong, moderate, and weak biofilm formation abilities in 32%, 33%, and 24% of the isolates, respectively. The most prevalent virulence gene was fimA (74%) followed by hlyF (68%), papA (44%), papC (32%), iroN (26%), and cnf (20%). The elevated levels of resistance to multiple antimicrobial agents, coupled with the co-presence of virulence genes and biofilm formation abilities, contribute to the persistence of UPEC-related infections, particularly in hospitalized patients. These findings underscore the necessity of implementing an effective program to control nosocomial UTIs caused by UPEC in the healthcare centers.

Revival of cryopreserved larvae from the important aquaculture species Pacific White Shrimp (Litopenaeus vannamei) using vitrification and ultra-rapid laser warming.

Cryopreservation of aquatic embryos or larvae is needed to help safeguard genetics from important wild and captive species, increase aquaculture output, and meet the global demand for protein. To this end, the development of a cryopreservation protocol for nauplius larvae of the commercially important aquaculture species Litopenaeus vannamei, or Pacific white shrimp, was pursued. Toxicity screening was performed using multiple cryoprotective agents (CPA), and a multi-constituent CPA cocktail was developed to achieve reliable vitrification of shrimp larvae encapsulated in 1.0-μL droplets containing gold nanoparticles. Vitrification and ultra-rapid laser warming were used to cryopreserve and revive nauplius-V stage larvae. Laser warming parameters were optimized to protect the pigmented eye spot from laser-induced ablation, and ice recrystallization inhibitors (IRIs) were tested to induce long-term survival. Approximately 54% of revived larvae resumed active swimming, but all failed to molt to the zoea-I stage of development or live beyond 15 hours post warming.

3-Factor prothrombin complex concentrate versus 4-factor prothrombin complex concentrate for the reversal of oral factor Xa inhibitors.

Multiple agents exist for the reversal of oral Factor Xa inhibitor (FXa) associated bleeding, including Coagulation FXa Recombinant, Inactivated zhzo (andexanet alfa) and 4-factor prothrombin complex concentrate (4F-PCC). While classified as a 3F-PCC product, Profilnine contains up to 35IU of Factor VII (per 100IU of Factor IX) in addition to therapeutic levels of Factors II, IX, and X, and has demonstrated a similar impact on prothrombin time and blood product usage in non-warfarin related bleeding. This was a retrospective, multicenter study at four medical centers of adult patients who presented with major bleeding associated with oral FXa inhibitors and received either 4F-PCC (n = 64) or 3F-PCC (n = 61). The primary outcome was hemostatic effectiveness. Secondary outcomes included the incidence of thromboembolism, in-hospital mortality, and length of stay. The most common indication for reversal was intracranial bleeding. For the primary outcome, 84% of all patients were rated as effective with no difference noted between the groups (p = 0.81). No significant difference between groups was found in the multivariable analysis adjusting for baseline differences between groups including race, total body weight, type of bleeding, and the use of antiplatelet therapy. There was no difference in the length of stay, in-hospital mortality, or the incidence of thromboembolism between the groups. Overall, no significant differences were found in the effectiveness or safety of 4F-PCC and 3F-PCC use in the management of oral FXa inhibitor-associated bleeding. Further investigations are warranted to explore the use of 3F-PCC for this indication and its safety and effectiveness.

GestureGPT: Toward Zero-Shot Free-Form Hand Gesture Understanding with Large Language Model Agents

Existing gesture interfaces only work with a fixed set of gestures defined either by interface designers or by users themselves, which introduces learning or demonstration efforts that diminish their naturalness. Humans, on the other hand, understand free-form gestures by synthesizing the gesture, context, experience, and common sense. In this way, the user does not need to learn, demonstrate, or associate gestures. We introduce GestureGPT, a free-form hand gesture understanding framework that mimics human gesture understanding procedures to enable a natural free-form gestural interface. Our framework leverages multiple Large Language Model agents to manage and synthesize gesture and context information, then infers the interaction intent by associating the gesture with an interface function. More specifically, our triple-agent framework includes a Gesture Description Agent that automatically segments and formulates natural language descriptions of hand poses and movements based on hand landmark coordinates. The description is deciphered by a Gesture Inference Agent through self-reasoning and querying about the interaction context (e.g., interaction history, gaze data), which is managed by a Context Management Agent. Following iterative exchanges, the Gesture Inference Agent discerns the user’s intent by grounding it to an interactive function. We validated our framework offline under two real-world scenarios: smart home control and online video streaming. The average zero-shot Top-1/Top-5 grounding accuracies are 44.79%/83.59% for smart home tasks and 37.50%/73.44% for video streaming tasks. We also provide an extensive discussion that includes rationale for model selection, generalizability, and future research directions for a practical system etc.

A Review on Secure Outsourcing and Privacy-Preserving Traffic Monitoring in Fog-Enabled VANETs

New possibilities for fog-based vehicle monitoring have emerged with the expansion of fog computing, but present privacy concerns provide a significant barrier that limits the extent to which vehicles can participate. Because of its potential to improve road network security and vehicle productivity, the field of Vehicle-based Ad hoc Networks (VANETs) is gaining prominence. The security problems with VANETs, such as data confidentiality and message access control are still need better solutions to provide better Quality of Service (QoS). The effectiveness of VANET networks is diminished due to their instability problem. Vehicles continually add requests to the Road Side Unit (RSU) queue whenever they want specific information. For ever-evolving networks like VANETs, better routing is a continual process. Fundamental problems arise in large-scale systems when centralized procedures are used to assign jobs to the nodes along a route. The present centralized system for computing and safety has many needs, including the protection of data storage, user authentication, access control, system availability across multiple network connections, and the provision of a real-time data flow overview. Distributed problem solving and work sharing between multiple agents can improve the system's scalability. This paper provides a brief survey on the secured outsourcing and privacy preservation-based traffic monitoring model with routing and task scheduling models in Fog-enabled VANETS. This survey presents the limitations of the traditional models that help the researchers design new solutions for secure outsourcing in VANETs.