Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022.

BACKGROUND & AIMS: We aimed to assess the secular trend of the global prevalence of Helicobacter pylori (H pylori) infection in adults and children/adolescents and to show its relation to that of gastric cancer incidence. METHODS: We performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. RESULTS: Of the 16,976 articles screened, 1748 articles from 111 countries were eligible for analysis. The crude global prevalence of H pylori has reduced from 52.6% (95% confidence interval [CI], 49.6%-55.6%) before 1990 to 43.9% (95% CI, 42.3%-45.5%) in adults during 2015 through 2022, but was as still as high as 35.1% (95% CI, 30.5%-40.1%) in children and adolescents during 2015 through 2022. Secular trend and multivariate regression analyses showed that the global prevalence of H pylori has declined by 15.9% (95% CI, -20.5% to -11.3%) over the last 3 decades in adults, but not in children and adolescents. Significant reduction of H pylori prevalence was observed in adults in the Western Pacific, Southeast Asian, and African regions. However, H pylori prevalence was not significantly reduced in children and adolescents in any World Health Organization regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H pylori infection has declined. CONCLUSIONS: The global prevalence of H pylori infection has declined during the last 3 decades in adults, but not in children and adolescents. The results raised the hypothesis that the public health drive to reduce the prevalence of H pylori as a strategy to reduce the incidence of gastric cancer in the population should be confirmed in large-scale clinical trials.

A mechanism for the strange metal phase in rare-earth intermetallic compounds.

SignificanceThe elusive strange metal phase (ground state) was observed in a variety of quantum materials, notably in f-electron-based rare-earth intermetallic compounds. Its emergence has remained unclear. Here, we propose a generic mechanism for this phenomenon driven by the interplay of the gapless fermionic short-ranged antiferromagnetic spin correlation and critical bosonic charge fluctuations near a Kondo breakdown quantum phase transition. It is manifested as a fluctuating Kondo-scattering-stabilized critical (gapless) fermionic spin liquid. It shows [Formula: see text] scaling in dynamical electron scattering rate, a signature of quantum criticality. Our results on quasilinear-in-temperature scattering rate and logarithmic-in-temperature divergence in specific heat coefficient as temperature vanishes were recently seen in CePd[Formula: see text]NixAl.

Critical role for ribonucleoside-diphosphate reductase subunit M2 in ALV-J-induced activation of Wnt/ß-catenin signaling via interaction with P27.

Avian leukemia virus subgroup J (ALV-J) causes various diseases associated with tumor formation and decreased fertility and induced immunosuppressive disease, resulting in significant economic losses in the poultry industry globally. Virus usually exploits the host cellular machinery for their replication. Although there are increasing evidences for the cellular proteins involving viral replication, the interaction between ALV-J and host proteins leading to the pivotal steps of viral life cycle are still unclear. Here, we reported that ribonucleoside-diphosphate reductase subunit M2 (RRM2) plays a critical role during ALV-J infection by interacting with capsid protein P27 and activating Wnt/ß-catenin signaling. We found that the expression of RRM2 is effectively increased during ALV-J infection, and that RRM2 facilitates ALV-J replication by interacting with viral capsid protein P27. Furthermore, ALV-J P27 activated Wnt/ß-catenin signaling by promoting ß-catenin entry into the nucleus, and RRM2 activated Wnt/ß-catenin signaling by enhancing its phosphorylation at Ser18 during ALV-J infection. These data suggest that the upregulation of RRM2 expression by ALV-J infection favors viral replication in host cells via activating Wnt/ß-catenin signaling. IMPORTANCE Our results revealed a novel mechanism by which RRM2 facilitates ALV-J growth. That is, the upregulation of RRM2 expression by ALV-J infection favors viral replication by interacting with capsid protein P27 and activating Wnt/ß-catenin pathway in host cells. Furthermore, the phosphorylation of serine at position 18 of RRM2 was verified to be the important factor regulating the activation of Wnt/ß-catenin signaling. This study provides insights for further studies of the molecular mechanism of ALV-J infection.

The SMAC mimetic GDC-0152 is a direct ABCB1-ATPase activity modulator and BIRC5 expression suppressor in cancer cells.

Upregulation of the multidrug efflux pump ABCB1/MDR1 (P-gp) and the anti-apoptotic protein BIRC5/Survivin promotes multidrug resistance in various human cancers. GDC-0152 is a DIABLO/SMAC mimetic currently being tested in patients with solid tumors. However, it is still unclear whether GDC-0152 is therapeutically applicable for patients with ABCB1-overexpressing multidrug-resistant tumors, and the molecular mechanism of action of GDC-0152 in cancer cells is still incompletely understood. In this study, we found that the potency of GDC-0152 is unaffected by the expression of ABCB1 in cancer cells. Interestingly, through in silico and in vitro analysis, we discovered that GDC-0152 directly modulates the ABCB1-ATPase activity and inhibits ABCB1 multidrug efflux activity at sub-cytotoxic concentrations (i.e., 0.25×IC50 or less). Further investigation revealed that GDC-0152 also decreases BIRC5 expression, induces mitophagy, and lowers intracellular ATP levels in cancer cells at low cytotoxic concentrations (i.e., 0.5×IC50). Co-treatment with GDC-0152 restored the sensitivity to the known ABCB1 substrates, including paclitaxel, vincristine, and YM155 in ABCB1-expressing multidrug-resistant cancer cells, and it also restored the sensitivity to tamoxifen in BIRC5-overexpressing tamoxifen-resistant breast cancer cells in vitro. Moreover, co-treatment with GDC-0152 restored and potentiated the anticancer effects of paclitaxel in ABCB1 and BIRC5 co-expressing xenograft tumors in vivo. In conclusion, GDC-0152 has the potential for use in the management of cancer patients with ABCB1 and BIRC5-related drug resistance. The findings of our study provide essential information to physicians for designing a more patient-specific GDC-0152 clinical trial program in the future.

Using a clinical narrative-aware pre-trained language model for predicting emergency department patient disposition and unscheduled return visits.

The increasing prevalence of overcrowding in Emergency Departments (EDs) threatens the effective delivery of urgent healthcare. Mitigation strategies include the deployment of monitoring systems capable of tracking and managing patient disposition to facilitate appropriate and timely care, which subsequently reduces patient revisits, optimizes resource allocation, and enhances patient outcomes. This study used âˆ¼ 250,000 emergency department visit records from Taipei Medical University-Shuang Ho Hospital to develop a natural language processing model using BlueBERT, a biomedical domain-specific pre-trained language model, to predict patient disposition status and unplanned readmissions. Data preprocessing and the integration of both structured and unstructured data were central to our approach. Compared to other models, BlueBERT outperformed due to its pre-training on a diverse range of medical literature, enabling it to better comprehend the specialized terminology, relationships, and context present in ED data. We found that translating Chinese-English clinical narratives into English and textualizing numerical data into categorical representations significantly improved the prediction of patient disposition (AUROC = 0.9014) and 72-hour unscheduled return visits (AUROC = 0.6475). The study concludes that the BlueBERT-based model demonstrated superior prediction capabilities, surpassing the performance of prior patient disposition predictive models, thus offering promising applications in the realm of ED clinical practice.

A comparison between intraosseous and intravenous access in patients with out-of-hospital cardiac arrest: A retrospective cohort study.

INTRODUCTION: The optimal vascular access for patients with out-of-hospital cardiac arrest (OHCA) remains controversial. Increasing evidence supports intraosseous (IO) access due to faster medication administration and higher first-attempt success rates compared to intravenous (IV) access. However, the impact on patient outcomes has been inconclusive. METHODS: This retrospective cohort study in Taoyuan City, Taiwan, from January 1, 2019, to December 31, 2022, included patients aged ≥18 years with non-traumatic OHCA resuscitated by emergency medical technician paramedics (EMT-Ps) with either IVs or IOs for final vascular access. The exclusion criteria were cardiac arrest en route to the hospital and resuscitation during the coronavirus pandemic (from May 1, 2022, to October 31, 2022). The primary and secondary outcomes were sustained ROSC (≥2 h) and cerebral performance category (CPC) 1-2, respectively. Univariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CI) for the primary analysis. Multivariable logistic regression was employed, with variables selected based on a p-value of <0.05 in the univariate analysis. The survival benefits of different insertion sites and subgroups like general ambulance teams (with a composition that includes fewer EMT-Ps and limited experience in using IO access) were also analyzed. RESULTS: A total of 2003 patients were enrolled; 1602 received IV access and 401 IO access. The median patient age was 70 years, and most were male (66.6%). Compared to patients receiving IV access, the adjusted odds ratios (aORs) for primary and secondary outcomes in patients with IOs were 0.83 (95% confidence interval [CI], 0.61-1.11; p = 0.20) and 0.96 (95% CI, 0.39-2.40; p = 0.93), respectively. Different insertion sites showed no outcome differences. In the subgroups of females and patients resuscitated by general ambulance teams, the aORs for sustained ROSC were 0.55 (95% CI, 0.33-0.92; p = 0.02) and 0.62 (95% CI, 0.41-0.94; p = 0.02), respectively. CONCLUSIONS: For patients with OHCA resuscitated by EMT-Ps, IO access was comparable to IV access regarding patient outcomes. However, in females and patients resuscitated by general ambulance teams, IV access might be favorable.

What is the best predictor of mortality in patients with type 2 diabetes and chronic kidney disease: mean, variability of HbA1c or HbA1c-Hemoglobin ratio?

AIM: Limitations in the measurement of glycated hemoglobin (HbA1c) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) result in uncertainty about the best predictor of mortality among these patients. Our study aimed to determine the association between the mean and average real variability (ARV) of HbA1c, as well as HbA1c-hemoglobin (HH) ratio with mortality among patients with T2D and CKD. MATERIALS AND METHODS: We identified 16,868 T2D patients with stage 3 or above CKD from outpatient visits during 2003-2018. We ascertained all-cause and cardiovascular mortality through linkage to Taiwan's National Death Registry. Mortality rates were estimated using the Poisson distribution, and we conducted Cox proportional hazards regressions to assess relative risks of mortality corresponding to the mean HbA1c, ARV of HbA1c and HH ratio. RESULTS: Compared to patients with a mean HbA1c of 7.0-7.9%, a mean HbA1c < 7.0% was persistently associated with highest risk of all-cause but not cardiovascular mortality after adjusting for confounders. On the contrary, patients with HbA1c-ARV in the second to fourth quartiles and HH ratios in the higher quartiles showed increased risk of all-cause and cardiovascular mortality compared to those in the first quartiles. CONCLUSIONS: HbA1c-ARV was more effective than mean HbA1c or HH ratio in predicting mortality in T2D patients with CKD. Apart from optimal glucose control, multidisciplinary care focusing on glycemic variability is essential for reducing mortality in these patients.

Intercellular viral spread and intracellular transposition of Drosophila gypsy.

It has become increasingly clear that retrotransposons (RTEs) are more widely expressed in somatic tissues than previously appreciated. RTE expression has been implicated in a myriad of biological processes ranging from normal development and aging, to age related diseases such as cancer and neurodegeneration. Long Terminal Repeat (LTR)-RTEs are evolutionary ancestors to, and share many features with, exogenous retroviruses. In fact, many organisms contain endogenous retroviruses (ERVs) derived from exogenous retroviruses that integrated into the germ line. These ERVs are inherited in Mendelian fashion like RTEs, and some retain the ability to transmit between cells like viruses, while others develop the ability to act as RTEs. The process of evolutionary transition between LTR-RTE and retroviruses is thought to involve multiple steps by which the element loses or gains the ability to transmit copies between cells versus the ability to replicate intracellularly. But, typically, these two modes of transmission are incompatible because they require assembly in different sub-cellular compartments. Like murine IAP/IAP-E elements, the gypsy family of retroelements in arthropods appear to sit along this evolutionary transition. Indeed, there is some evidence that gypsy may exhibit retroviral properties. Given that gypsy elements have been found to actively mobilize in neurons and glial cells during normal aging and in models of neurodegeneration, this raises the question of whether gypsy replication in somatic cells occurs via intracellular retrotransposition, intercellular viral spread, or some combination of the two. These modes of replication in somatic tissues would have quite different biological implications. Here, we demonstrate that Drosophila gypsy is capable of both cell-associated and cell-free viral transmission between cultured S2 cells of somatic origin. Further, we demonstrate that the ability of gypsy to move between cells is dependent upon a functional copy of its viral envelope protein. This argues that the gypsy element has transitioned from an RTE into a functional endogenous retrovirus with the acquisition of its envelope gene. On the other hand, we also find that intracellular retrotransposition of the same genomic copy of gypsy can occur in the absence of the Env protein. Thus, gypsy exhibits both intracellular retrotransposition and intercellular viral transmission as modes of replicating its genome.

The Impact of Thallium Exposure in Public Health and Molecular Toxicology: A Comprehensive Review.

This review offers a synthesis of the current understanding of the impact of low-dose thallium (Tl) on public health, specifically emphasizing its diverse effects on various populations and organs. The article integrates insights into the cytotoxic effects, genotoxic potential, and molecular mechanisms of thallium in mammalian cells. Thallium, a non-essential heavy metal present in up to 89 different minerals, has garnered attention due to its adverse effects on human health. As technology and metallurgical industries advance, various forms of thallium, including dust, vapor, and wastewater, can contaminate the environment, extending to the surrounding air, water sources, and soil. Moreover, the metal has been identified in beverages, tobacco, and vegetables, highlighting its pervasive presence in a wide array of food sources. Epidemiological findings underscore associations between thallium exposure and critical health aspects such as kidney function, pregnancy outcomes, smoking-related implications, and potential links to autism spectrum disorder. Thallium primarily exerts cellular toxicity on various tissues through mitochondria-mediated oxidative stress and endoplasmic reticulum stress. This synthesis aims to shed light on the intricate web of thallium exposure and its potential implications for public health, emphasizing the need for vigilant consideration of its risks.

A Preliminary Investigation of the Roles of Endometrial Cells in Endometriosis Development via In Vitro and In Vivo Analyses.

Endometriosis is a complex gynecological disease that affects more than 10% of women in their reproductive years. While surgery can provide temporary relief from women's pain, symptoms often return in as many as 75% of cases within two years. Previous literature has contributed to theories about the development of endometriosis; however, the exact pathogenesis and etiology remain elusive. We conducted a preliminary investigation into the influence of primary endometrial cells (ECs) on the development and progression of endometriosis. In vitro studies, they were involved in inducing Lipopolysaccharide (LPS) in rat-isolated primary endometrial cells, which resulted in increased nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) mRNA gene expression (quantitative polymerase chain reaction analysis, qPCR) and protein expression (western blot analysis). Additionally, in vivo studies utilized autogenic and allogeneic transplantations (rat to rat) to investigate endometriosis-like lesion cyst size, body weight, protein levels (immunohistochemistry), and mRNA gene expression. These studies demonstrated that estrogen upregulates the gene and protein regulation of cytoskeletal (CK)-18, transforming growth factor-ß (TGF-ß), VEGF, and tumor necrosis factor (TNF)-α, particularly in the peritoneum. These findings may influence cell proliferation, angiogenesis, fibrosis, and inflammation markers. Consequently, this could exacerbate the occurrence and progression of endometriosis.

Upregulation of occludin by cytolethal distending toxin facilitates Glaesserella parasuis adhesion to respiratory tract cells.

Virulent Glaesserella parasuis may engender systemic infection characterized by fibrinous polyserositis and pneumonia. G. parasuis causes systemic disease through upper respiratory tract infection, but the mechanism has not been fully characterized. Tight junction (TJ) proteins maintain the integrity and impermeability of the epithelial barriers. In this work, we applied the recombinant cytolethal distending toxin (CDT) holotoxin and cdt-deficient mutants to assess whether CDT interacted with TJ proteins of airway tract cells. Our results indicated that CDT induced the TJ occludin (OCLN) expression in newborn pig tracheal epithelial cells within the first 3 hours of bacterial infection, followed by a significant decrease. Overexpression of OCLN in target cells made them more susceptible to G. parasuis adhesion, whereas ablation of OCLN expression by CRISPR/Cas 9 gene editing technology in target cells decreased their susceptibility to bacterial adhesion. In addition, CDT treatment could upregulate the OCLN levels in the lung tissue of C57/BL6 mice. In summary, highly virulent G. parasuis strain SC1401 stimulated the tight junction expression, resulting in higher bacterial adhesion to respiratory tract cells, and this process is closely related to CDT. Our results may provide novel insights into G. parasuis infection and CDT-mediated pathogenesis.

TMEM211 Promotes Tumor Progression and Metastasis in Colon Cancer.

Colon cancer is the third most important cancer type, leading to a remarkable number of deaths, indicating the necessity of new biomarkers and therapeutic targets for colon cancer patients. Several transmembrane proteins (TMEMs) are associated with tumor progression and cancer malignancy. However, the clinical significance and biological roles of TMEM211 in cancer, especially in colon cancer, are still unknown. In this study, we found that TMEM211 was highly expressed in tumor tissues and the increased TMEM211 was associated with poor prognosis in colon cancer patients from The Cancer Genome Atlas (TCGA) database. We also showed that abilities regarding migration and invasion were reduced in TMEM211-silenced colon cancer cells (HCT116 and DLD-1). Moreover, TMEM211-silenced colon cancer cells showed decreased levels of Twist1, N-cadherin, Snail and Slug but increased levels of E-cadherin. Levels of phosphorylated ERK, AKT and RelA (NF-κB p65) were also decreased in TMEM211-silenced colon cancer cells. Our findings indicate that TMEM211 regulates epithelial-mesenchymal transition for metastasis through coactivating the ERK, AKT and NF-κB signaling pathways, which might provide a potential prognostic biomarker or therapeutic target for colon cancer patients in the future.

Microlens array device for laser light shaping in laser scanning smart headlights.

We present, what we believe to be, a novel microlens array (MLA) scheme for laser light shaping in laser scanning smart headlight. The laser spot has a Gaussian distribution that may reach a high peak power density in the central part, which is called hot spot. When the laser beam is applied to a phosphor plate for luminous conversion, the hot spot of Gaussian beam causes thermal quench and decreases luminous efficacy. To avoid this effect, an MLA is used, so as to achieve a uniform energy distribution. In this study, we propose a laser scanning smart headlight fabricated by a new MLA structure, with an arrangement providing both light uniformity and shaping. The novel MLA is designed by two-dimensional micro-concave lens array yielding a flat-top beam. The flexible fabrication process employs laser drilling to shape the micro-hole array on the glass substrate surface and then etch it to form MLA without requiring any mask lithography process. The full-width half maximum (FWHM) of light output distribution can be adjusted by the glass etching parameters, and the light distribution could be controlled by the arranged layout of the array. Thus, beams with FWHM divergence ranging from 5° to 34° has been fabricated and characterized. The typical pixel shape is a rectangle with two different FWHMs in two orthogonal directions, and the fabrication method achieves this goal as well. This novel design and unique maskless process of the MLAs is a promising tool for development the next generation laser scanning smart headlight.

Pasteurella multocida causes liver injury in ducks by mediating inflammatory, apoptotic and autophagic pathways.

Pasteurella multocida.(PM) infection is a major cause of avian cholera, but the pathogenesis of the disease is unknown. The purpose of this study was to further understand the host response to infection by using a duck model of PM, 20 female ducks were divided into two groups (n = 10). One group was infected with PM, while the other served as an uninfected control group. The ducks were observed after infection and samples were collected for testing. In this study, we report the mechanism of PM-induced inflammation to further mediate apoptosis and autophagic signaling pathways in liver cells. Our results demonstrated that PM infection initially induces hemorrhagic and necrotic lesions in the liver tissue of duck, promoting inflammasome assembly and release, triggering inflammation. The TLR4/NF-κB axis activated and interacted with multiple inflammation-related proteins, including TNF-α and IL-1ß, which affected apoptosis and autophagy. Tumor necrosis factor induced hepatocyte apoptosis was implicated in a wide range of liver diseases; the release of TNF-α and activation with NF-κB further incite apoptotic pathways,such as Bax/BCL2/caspase to promote apoptotic genes APAF1, Bax, Caspase3, BCL-2, p53, and Cytc expression. Finally, PM-induced autophagy suppressed liver injury by promoting the Beclin-1, LC3B, p62, and mTOR. Thus, liver injury caused by PM via promoting autophagy was induced. In conclusion, we analyzed the liver injury of ducks infected with PM, and confirmed that inflammation appeared in the liver; this was followed by the intricate interplay between inflammation, apoptosis, and autophagy signaling pathways. The observed results provided a reference basis for studying pathogenic mechanisms of PM-host interactions.

Antiproliferative and apoptotic effects of telmisartan in human glioma cells.

Glioblastoma is the most common primary central nervous system tumor in adults. Angiotensin II receptor blockers (ARBs) are broadly applied to treat hypertension. Moreover, research has revealed that ARBs have the capacity to suppress the growth of several cancer types. In this study, we assessed the effects of three ARBs with the ability to cross the blood brain barrier (telmisartan, valsartan and fimasartan) on cell proliferation in three glioblastoma multiforme (GBM) cell lines. Telmisartan markedly suppressed the proliferation, migration, and invasion of these three GBM cell lines. Microarray data analysis revealed that telmisartan regulates DNA replication, mismatch repair, and the cell cycle pathway in GBM cells. Furthermore, telmisartan induced G0/G1 phase arrest and apoptosis. The bioinformatic analysis and western blotting results provide evidence that SOX9 is a downstream target of telmisartan. Telmisartan also suppressed tumor growth in vivo in an orthotopic transplant mouse model. Therefore, telmisartan is a potential treatment for human GBM.

Blood neurofilament light chain as a surrogate marker for dystonia.

BACKGROUND AND PURPOSE: Dystonia is a heterogeneous movement disorder, and it remains unclear whether neurodegeneration is involved. Neurofilament light chain (NfL) is a biosignature of neurodegeneration. We aimed to investigate whether plasma NfL levels were elevated and associated with disease severity in patients with dystonia. METHOD: We enrolled 231 unrelated dystonia patients (isolated dystonia n = 203; combined dystonia n = 28) and 54 healthy controls from movement disorder clinics. Clinical severity was evaluated using the Fahn Marsden Dystonia Rating Scale, the Unified Dystonia Rating Scale, and the Global Dystonia Rating Scale. Blood NfL levels were measured by single-molecule array. RESULTS: Plasma NfL levels were significantly higher in those with generalized dystonia compared to those with focal dystonia (20.1 ± 8.8 vs. 11.7 ± 7.2 pg/mL; p = 0.01) or controls (p < 0.01), while the level was comparable between the focal dystonia group and controls (p = 0.08). Furthermore, the dystonia combined with parkinsonism group had higher NfL levels than the isolated dystonia group (17.4 ± 6.2 vs. 13.5 ± 7.5 pg/mL; p = 0.04). Notably, whole-exome sequencing was performed in 79 patients and two patients were identified as having likely pathogenic variants: one had a heterozygous c.122G>A (p.R41H) variant in THAP1 (DYT6) and the other carried a c.1825G>A (p.D609N) substitution in ATP1A3 (DYT12). No significant correlation was found between plasma NfL levels and dystonia rating scores. CONCLUSION: Plasma NfL levels are elevated in patients with generalized dystonia and dystonia combined with parkinsonism, suggesting that neurodegeneration is involved in the disease process of this subgroup of patients.

Clinical narrative-aware deep neural network for emergency department critical outcome prediction.

Since early identification of potential critical patients in the Emergency Department (ED) can lower mortality and morbidity, this study seeks to develop a machine learning model capable of predicting possible critical outcomes based on the history and vital signs routinely collected at triage. We compare emergency physicians and the predictive performance of the machine learning model. Predictors including patients' chief complaints, present illness, past medical history, vital signs, and demographic data of adult patients (aged ≥ 18 years) visiting the ED at Shuang-Ho Hospital in New Taipei City, Taiwan, are extracted from the hospital's electronic health records. Critical outcomes are defined as in-hospital cardiac arrest (IHCA) or intensive care unit (ICU) admission. A clinical narrative-aware deep neural network was developed to handle the text-intensive data and standardized numerical data, which is compared against other machine learning models. After this, emergency physicians were asked to predict possible clinical outcomes of thirty visits that were extracted randomly from our dataset, and their results were further compared to our machine learning model. A total of 4,308 (2.5 %) out of the 171,275 adult visits to the ED included in this study resulted in critical outcomes. The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) of our proposed prediction model is 0.874 and 0.207, respectively, which not only outperforms the other machine learning models, but even has better sensitivity (0.95 vs 0.41) and accuracy (0.90 vs 0.67) as compared to the emergency physicians. This model is sensitive and accurate in predicting critical outcomes and highlights the potential to use predictive analytics to support post-triage decision-making.

Marine Sponge-Derived Alkaloid Induces Mitochondrial Dysfunction and Inhibits the PI3K/AKT/mTOR Signaling Pathway against Burkitt's Lymphoma.

Burkitt's lymphoma (BL) has a particularly extremely poor prognosis and the fastest growth rate among human tumors, and the development of new drugs for the treatment of BL is urgently needed. In this study, the cytotoxic properties of 3,7-bis(3,5-dimethylphenyl)-aaptamine (AP-51), a new semisynthetic alkaloid derived from the marine natural product aapatamine, were investigated using BL cell lines. Our results showed that AP-51 inhibited the proliferation of Daudi and Raji cells with IC50 values of 3.48 and 2.07 µM, respectively. Flow cytometry and Western blot analyses showed that AP-51 initiated G0/G1 phase arrest by modulating the expression of cyclin-dependent kinases (CDKs). AP-51 also induced apoptosis, as demonstrated by nuclear fragmentation, downregulation of BCL-XL and Mcl-1, and upregulation of cleaved caspase-9, cleaved caspase-3, cleaved-PARP, and cytochrome c, the markers of apoptosis regulated via the mitochondrial pathway. When it comes to mitochondria, AP-51 treatment also significantly increased the levels of intracellular mitochondrial superoxide, decreased ATP content, and reduced the expression of ATP synthase, as well as the expression of the mitochondrial respiratory chain complexes. Finally, AP-51 treatment significantly inhibited the PI3K/AKT/mTOR signaling pathway, which was shown to be associated with the induction of apoptosis. Collectively, these findings indicated that AP-51 initiated cell cycle arrest, induced apoptosis, caused mitochondrial dysfunction, and decreased the phosphorylation of PI3K/AKT/mTOR signaling pathway-related proteins and the protein levels of C-MYC, suggesting that AP-51 has therapeutic potential as a possible treatment for Burkitt's lymphoma.

Epinephrine administration in adults with out-of-hospital cardiac arrest: A comparison between intraosseous and intravenous route.

INTRODUCTION: The benefits and risks of the intraosseous (IO) route for vascular access in patients with out-of-hospital cardiac arrest (OHCA) remain controversial. This study compares the success rates of establishing the access route, epinephrine administration rates, and time-to-epinephrine between adult patients with OHCA with IO access and those with intravenous (IV) access established by paramedics in the prehospital setting. METHODS: This was a retrospective study conducted by the San-Min station of Taoyuan Fire Department. Data for IV access were collected between January 1, 2020, and December 31, 2020. Data for IO access were collected between January 1, 2021, and March 10, 2021. Inclusion criteria were adult patients with OHCA who received on-scene resuscitation attempts and in whom either IV or IO route access was established by paramedics. Exclusion criteria were missing data, return of spontaneous circulation before establishing vascular access, cardiac arrest en route to hospital, patients not resuscitated, and OHCA unidentified by the dispatcher. Exposure was defined as IV route vs. IO route (EZ-IO®). The outcome measurements were per-patient based success rates of route establishment (successes/attempts), administration rates of epinephrine (epinephrine administered per case/enrolled OHCAs), and odds ratios of IV versus IO on epinephrine administration. We used nonparametric Mann-Whitney rank sum tests for the analysis in continuous variables and Fisher's exact tests for the analysis of categorical variables and the outcomes. Firth logistic regression method was used for sparse data. Factors associated with epinephrine administration other than vascular access were also analyzed. Time-to-epinephrine (defined as time from paramedic arrival to epinephrine injection) was reviewed and calculated by two independent observers and the Kaplan-Meier method was used to compare the two access routes. RESULTS: A total of 112 adult patients were enrolled in the analysis, including 71 men and 41 women, with an average age of 67 years. There were 90 IV access cases and 22 IO access cases. The groups were compared for median success rates of route establishment (33% vs. 100%, P < 0.001) and administration rates of epinephrine (52% vs. 100%, P < 0.001). The adjusted odds ratio of IO versus IV was 32.445, 95% confidence interval (CI) of 1.844-570.861. Time-to-epinephrine was significantly shorter in the cumulative time-event analysis by the Kaplan-Meier method (P < 0.001). CONCLUSION: The IO route was significantly associated with higher success rates of route establishment, epinephrine administration, and shorter time-to-epinephrine in the prehospital resuscitation of adult patients with OHCA.

Consumers' longitudinal health information needs and seeking: a scoping review.

Needing and seeking health information often is a longitudinal everyday life information behavior that involves the use of technology. However, no reviews of consumers' longitudinal health information needs (HIN) and health information-seeking (HIS) behavior have been conducted. We performed a scoping review to address this gap. Specifically, we surveyed the characteristics, timeline construction and research findings of studies investigating consumers' longitudinal HIN and HIS. Initial searches were conducted in November 2019 and updated in July 2022. A total of 128 papers were identified, reviewed and analyzed using content and thematic analyses. Results showed that most papers were quantitative, conducted in the USA, related to cancer, conducted during the diagnosis and treatment phases, and followed preset time intervals. Findings concerning the development patterns of consumers' HIN degrees and HIS effort were mixed (i.e. increasing, decreasing or being consistent over time). They seemed to be shaped by factors such as health conditions, data collection methods and the length of data collection. Consumers' use of sources changes depending on health status and source accessibility; their medical terminologies seem to expand over time. HIS has a strong emotional dimension which may lead to adaptive or maladaptive information behaviors (e.g. information avoidance). Overall, the results revealed a lack of understanding of HIN and HIS from a longitudinal perspective, particularly along health condition progression and coping trajectories. There is also a lack of understanding of the role of technologies in the longitudinal HIS process.