Large Language Models for Intent-Driven Session Recommendations

Intent-aware session recommendation (ISR) is pivotal in discerning user intents within sessions for precise predictions. Traditional approaches, however, face limitations due to their presumption of a uniform number of intents across all sessions. This assumption overlooks the dynamic nature of user sessions, where the number and type of intentions can significantly vary. In addition, these methods typically operate in latent spaces, thus hinder the model's transparency.Addressing these challenges, we introduce a novel ISR approach, utilizing the advanced reasoning capabilities of large language models (LLMs). First, this approach begins by generating an initial prompt that guides LLMs to predict the next item in a session, based on the varied intents manifested in user sessions. Then, to refine this process, we introduce an innovative prompt optimization mechanism that iteratively self-reflects and adjusts prompts. Furthermore, our prompt selection module, built upon the LLMs' broad adaptability, swiftly selects the most optimized prompts across diverse domains. This new paradigm empowers LLMs to discern diverse user intents at a semantic level, leading to more accurate and interpretable session recommendations. Our extensive experiments on three real-world datasets demonstrate the effectiveness of our method, marking a significant advancement in ISR systems

UC-Secure Source Routing Protocol

The multi-path routing scheme provides reliable guarantee for mobile ad hoc network. A new method is proposed that is using to analyze the security of multi-path routing protocol within the framework of Universally Composable (UC) security. Based on the topological model that there exist adversarial nodes, the concept of plausible route is extended and the definition of plausible-route set is presented. Plausible-route set is used in description of the multi-path routing for Ad hoc network, and a formal security definition based on UC-RP is given. A provably Security Multiple Node-Disjoint Paths source routing (SMNDP) is proposed and address secure fault issue of MNDP in the active adversary model. The new approach shows that the security of SMNDP can be reduced to the security of the message authentication code and the digital signature. SMNDP implements the correctness of route discovery process, the authentication of nodes identifier and the integrality of route information

mTORC1 controls lysosomal Ca²⁺ release through the two-pore channel TPC2

The ion channel TPC2 is required for Ca 2+ mobilization from lysosomes in response to mTORC1 inhibition and to NAADP. </jats:p

LRRC8 family proteins within lysosomes regulate cellular osmoregulation and enhance cell survival to multiple physiological stresses

LRRC8 family proteins on the plasma membrane play a critical role in cellular osmoregulation by forming volume-regulated anion channels (VRACs) necessary to prevent necrotic cell death.We demonstrate that intracellular LRRC8 proteins acting within lysosomes also play an essential role in cellular osmoregulation. LRRC8 proteins on lysosome membranes generate large lysosomal volume-regulated anion channel (Lyso-VRAC) currents in response to low cytoplasmic ionic strength conditions. When a double-leucine L706L707 motif at the C terminus of LRRC8A was mutated to alanines, normal plasma membrane VRAC currents were still observed, but Lyso-VRAC currents were absent. We used this targeting mutant, as well as pharmacological tools, to demonstrate that Lyso-VRAC currents are necessary for the formation of large lysosome-derived vacuoles, which store and then expel excess water to maintain cytosolic water homeostasis. Thus, Lyso-VRACs allow lysosomes of mammalian cells to act as the cell`s “bladder.” When Lyso-VRAC current was selectively eliminated, the extent of necrotic cell death to sustained stress was greatly increased, not only in response to hypoosmotic stress, but also to hypoxic and hypothermic stresses. Thus Lyso-VRACs play an essential role in enabling cells to mount successful homeostatic responses to multiple stressors

SKP2 Promotes Hepatocellular Carcinoma Progression Through Nuclear AMPK-SKP2-CARM1 Signaling Transcriptionally Regulating Nutrient-Deprived Autophagy Induction

Background/Aims: SKP2 overexpression has been associated with poor prognosis in numerous cancers. The mechanisms of autophagy in the tumor pathogenesis have been a research focus recently. How the SKP2 involved in autophagy expresses oncogenic characteristics, especially in HCC, are largely unclear. Methods: The expression of SKP2 was detected by qPCR, Western blot, Immunohistochemical (IHC) and Immunofluorescence (IF) techniques. SKP2 was knocked down or overexpressed by lentivirus transfection in HCC cells. Functional assays such as CCK8 assays, transwell migration and invasion assays, and colony formation assays were performed to determine the role of SKP2 in HCC. Furthermore, autophagy was induced by glucose deprivation in HCC cells followed by monitoring of the levels and distributions of SKP2, CARM1 and AMPK. Results: Our data showed that SKP2 levels were significantly increased in HCC cell lines and HCC tissues rather than corresponding normal liver tissues, and augmented SKP2 levels were statistically correlated with tumor grade, size and metastases. By up-regulation or down-regulation of SKP2 in HCC cells, we confirmed that SKP2 encourages proliferation, migration, invasion, and colony formation. We then found that SKP2 was inhibited, CARM1 increased and AMPKα2 became activated in the nucleus under glucose deprivation induced autophagy. Moreover, we discovered that SKP2 was repressing CARM1 in the nucleus under nutrient-sufficient conditions in HCC. Conclusions: We show that SKP2 promotes HCC progression and its nuclear functions of autophagy induction with CARM1 and AMPK, which may provide a potential target for HCC therapy

Aphrodisiac Use Associated with HIV Infection in Elderly Male Clients of Low-Cost Commercial Sex Venues in Guangxi, China: A Matched Case-Control Study

Background: Rising HIV infection rates have been observed among elderly people in Guangxi, China. Inexpensive aphrodisiacs are available for purchase in suburban and rural areas. This study aims to investigate the association between aphrodisiac use and increased HIV risk for middle-aged and elderly men in Guangxi. Methods: A matched case-control study of aphrodisiac use-associated HIV infection was performed among male subjects over 50 years old who were clients of low-cost commercial sex venues in Guangxi. The cases were defined as clients who were HIV-positive and two controls were selected for each case. The cases and the controls were matched on the visited sex venue, age (±3 years), number of years of purchasing sex (±3 years), and educational attainment. Subjects were interviewed and tested for HIV. Paired t-test or McNemar Chi-squared test were used to compare the characteristics between the cases and controls. A stepwise conditional logistic regression was used to identify risk factors associated with HIV infection. Findings: This study enrolled 103 cases and 206 controls. Aphrodisiac use (P = 0.02, odds ratio (OR) = 1.81, 95% CI = 1.08–3.04), never using condom during commercial sex encounter (P = 0.03, odds ratio (OR) = 1.82, 95% CI = 1.08–3.07), and lacking a stable partner (P = 0.03, odds ratio (OR) = 1.76, 95% CI = 1.05–2.98) were found to be risk factors for HIV infection among the study groups. For subjects reporting aphrodisiac use, the frequency of purchasing sex was positively correlated with the frequency of aphrodisiac use (r = 0.3; p = 0.02). Conclusions: Aphrodisiac use was significantly associated with increased HIV infection risk in men over 50 years old who purchased commercial sex in the suburban and rural areas of Guangxi. Further research and interventions should address the links between aphrodisiac use, commercial sex work, condom use, and increased HIV transmission

Acute effects of fine particulate matter (PM2.5) on hospital admissions for cardiovascular disease in Beijing, China: A time-series study

Background Air pollution and cardiovascular disease are increasing problems in China. However, the short-term association between fine particulate matter (PM2.5) and cardiovascular disease (CVD) is not well documented. The purpose of this study is to estimate the short-term effects of PM2.5 on CVD admissions in Beijing, China. Methods In total, 460,938 electronic hospitalization summary reports for CVD between 2013 and 2017 were obtained. A generalized additive model using a quasi-Poisson distribution was used to investigate the association between exposure to PM2.5 and hospitalizations for total and cause-specific CVD, including coronary heart disease (CHD), atrial fibrillation (AF), and heart failure (HF) after controlling for the season, the day of the week, public holidays, and weather conditions. A stratified analysis was also conducted for age (18–64 and ≥ 65 years), sex and season. Results For every 10 μg/m3 increase in the PM2.5 concentration from the previous day to the current (lag 0–1) there was a significant increase in total CVD admissions (0.30, 95% CI: 0.20, 0.39%), with a strong association for older adults (aged ≥65 years), CHD (0.34, 95% CI: 0.22 to 0.45%) and AF (0.29, 95% CI, 0.03 to 0.55%). However, the observed increased risk was not statistically significant for HF hospitalizations. The associations in the single-pollutant models were robust to the inclusion of other pollutants in a two-pollutant model. No differences were found after stratification by sex and season. Conclusions Exposure to PM2.5 increased the risk of hospitalizations from CVD, especially for CHD, and appeared to have more influence in the elderly. Precautions and protective measures and efforts to reduce exposure to PM2.5 should be strengthened, especially for the elderly

Cognitive impairment and risk of all-cause and cardiovascular disease mortality over 20-year follow-up: Results from the BLSA

Background-Cognitive impairment may increase the risk of all-cause and cardiovascular disease (CVD) mortality. This study examined the association between cognitive function and risk of all-cause and CVD mortality among the elderly in Beijing, China. Methods and Results-A total of 1996 participants aged ≥55 years at baseline were enrolled from the BLSA (Beijing Longitudinal Study of Aging). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and participants were categorized as

Oxaliplatin Depolarizes the IB4– Dorsal Root Ganglion Neurons to Drive the Development of Neuropathic Pain Through TRPM8 in Mice

Use of chemotherapy drug oxaliplatin is associated with painful peripheral neuropathy that is exacerbated by cold. Remodeling of ion channels including TRP channels in dorsal root ganglion (DRG) neurons contribute to the sensory hypersensitivity following oxaliplatin treatment in animal models. However, it has not been studied if TRP channels and membrane depolarization of DRG neurons serve as the initial ionic/membrane drives (such as within an hour) that contribute to the development of oxaliplatin-induced neuropathic pain. In the current study, we studied in mice (1) in vitro acute effects of oxaliplatin on the membrane excitability of IB4+ and IB4– subpopulations of DRG neurons using a perforated patch clamping, (2) the preventative effects of a membrane-hyperpolarizing drug retigabine on oxaliplatin-induced sensory hypersensitivity, and (3) the preventative effects of TRP channel antagonists on the oxaliplatin-induced membrane hyperexcitability and sensory hypersensitivity. We found (1) IB4+ and IB4– subpopulations of small DRG neurons displayed previously undiscovered, substantially different membrane excitability, (2) oxaliplatin selectively depolarized IB4– DRG neurons, (3) pretreatment of retigabine largely prevented oxaliplatin-induced sensory hypersensitivity, (4) antagonists of TRPA1 and TRPM8 channels prevented oxaliplatin-induced membrane depolarization, and (5) the antagonist of TRPM8 largely prevented oxaliplatin-induced sensory hypersensitivity. These results suggest that oxaliplatin depolarizes IB4– neurons through TRPM8 channels to drive the development of neuropathic pain and targeting the initial drives of TRPM8 and/or membrane depolarization may prevent oxaliplatin-induce neuropathic pain

Identification and validation of IgG N-glycosylation biomarkers of esophageal carcinoma

Introduction: Altered Immunoglobulin G (IgG) N-glycosylation is associated with aging, inflammation, and diseases status, while its effect on esophageal squamous cell carcinoma (ESCC) remains unknown. As far as we know, this is the first study to explore and validate the association of IgG N-glycosylation and the carcinogenesis progression of ESCC, providing innovative biomarkers for the predictive identification and targeted prevention of ESCC. Methods: In total, 496 individuals of ESCC (n=114), precancerosis (n=187) and controls (n=195) from the discovery population (n=348) and validation population (n=148) were recruited in the study. IgG N-glycosylation profile was analyzed and an ESCC-related glycan score was composed by a stepwise ordinal logistic model in the discovery population. The receiver operating characteristic (ROC) curve with the bootstrapping procedure was used to assess the performance of the glycan score. Results: In the discovery population, the adjusted OR of GP20 (digalactosylated monosialylated biantennary with core and antennary fucose), IGP33 (the ratio of all fucosylated monosyalilated and disialylated structures), IGP44 (the proportion of high mannose glycan structures in total neutral IgG glycans), IGP58 (the percentage of all fucosylated structures in total neutral IgG glycans), IGP75 (the incidence of bisecting GlcNAc in all fucosylated digalactosylated structures in total neutral IgG glycans), and the glycan score are 4.03 (95% CI: 3.03-5.36, P \u3c 0.001), 0.69 (95% CI: 0.55-0.87, P \u3c 0.001), 0.56 (95% CI: 0.45-0.69, P \u3c 0.001), 0.52 (95% CI: 0.41-0.65, P \u3c 0.001), 7.17 (95% CI: 4.77-10.79, P \u3c 0.001), and 2.86 (95% CI: 2.33-3.53, P \u3c 0.001), respectively. Individuals in the highest tertile of the glycan score own an increased risk (OR: 11.41), compared with those in the lowest. The average multi-class AUC are 0.822 (95% CI: 0.786-0.849). Findings are verified in the validation population, with an average AUC of 0.807 (95% CI: 0.758-0.864). Discussion: Our study demonstrated that IgG N-glycans and the proposed glycan score appear to be promising predictive markers for ESCC, contributing to the early prevention of esophageal cancer. From the perspective of biological mechanism, IgG fucosylation and mannosylation might involve in the carcinogenesis progression of ESCC, and provide potential therapeutic targets for personalized interventions of cancer progression