Association of lactate-to-albumin ratio with in-hospital and intensive care unit mortality in patients with intracerebral hemorrhage

BackgroundIntracerebral hemorrhage (ICH) is a severe stroke subtype with a high mortality rate; the lactate-to-albumin ratio (LAR) is a new biomarker for predicting clinical outcomes in patients with ICH. However, the relationship between LAR and mortality in patients with ICH treated in the intensive care unit (ICU) remains controversial. Therefore, in this study, we aimed to investigate the association between LAR and in-hospital and ICU mortality in patients with ICH.MethodsPatients with ICH were selected from the Medical Information Mart for Intensive Care III (MIMIC-III) database; their clinical information, including baseline characteristics, vital signs, comorbidities, laboratory test results, and scoring systems, was extracted. Univariate and multivariate Cox proportional hazards analyses were used to investigate the association of LAR with in-hospital and ICU mortality. The maximum selection statistical method and subgroup analysis were used to investigate these relationships further. Kaplan–Meier (KM) analysis was used to draw survival curves.ResultsThis study enrolled 237 patients with ICH whose lactate and albumin levels, with median values of 1.975 and 3.6 mg/dl, respectively, were measured within the first 24 h after ICU admission. LAR had an association with increased risk of in-hospital mortality [unadjusted hazards ratio (HR), 1.79; 95% confidence interval (CI), 1.32–2.42; p < 0.001] and ICU mortality (unadjusted HR, 1.88; 95% CI, 1.38–2.55; p < 0.001). A cut-off value of 0.963 mg/dl was used to classify patients into high LAR (≥0.963) and low LAR (<0.963) groups, and survival curves suggested that those two groups had significant survival differences (p = 0.0058 and 0.0048, respectively). Furthermore, the high LAR group with ICH had a significantly increased risk of in-hospital and ICU mortality compared to the low LAR group.ConclusionOur study suggests that a high LAR is associated with an increased risk of in-hospital and ICU mortality in patients with ICH. Thus, the LAR is a useful prognostic predictor of clinical outcomes in patients with ICH

Self-partitioning SlipChip for slip-induced droplet formation and human papillomavirus viral load quantification with digital LAMP

Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide, and persistent HPV infection can cause warts and even cancer. Nucleic acid analysis of HPV viral DNA can be very informative for the diagnosis and monitoring of HPV. Digital nucleic acid analysis, such as digital PCR and digital isothermal amplification, can provide sensitive detection and precise quantification of target nucleic acids, and its utility has been demonstrated in many biological research and medical diagnostic applications. A variety of methods have been developed for the generation of a large number of individual reaction partitions, a key requirement for digital nucleic acid analysis. However, an easily assembled and operated device for robust droplet formation without preprocessing devices, auxiliary instrumentation or control systems is still highly desired. In this paper, we present a self-partitioning SlipChip (sp-SlipChip) microfluidic device for the slip-induced generation of droplets to perform digital loop-mediated isothermal amplification (LAMP) for the detection and quantification of HPV DNA. In contrast to traditional SlipChip methods, which require the precise alignment of microfeatures, this sp-SlipChip utilized a design of “chain-of-pearls” continuous microfluidic channel that is independent of the overlapping of microfeatures on different plates to establish the fluidic path for reagent loading. Initiated by a simple slipping step, the aqueous solution can robustly self-partition into individual droplets by capillary pressure-driven flow. This advantage makes the sp-SlipChip very appealing for the point-of-care quantitative analysis of viral load. As a proof of concept, we performed digital LAMP on an sp-SlipChip to quantify human papillomaviruses (HPVs) 16 and 18 and tested this method with fifteen anonymous clinical samples

Beam Retrieval: General End-to-End Retrieval for Multi-Hop Question Answering

Multi-hop QA involves finding multiple relevant passages and step-by-step reasoning to answer complex questions. While previous approaches have developed retrieval modules for selecting relevant passages, they face challenges in scenarios beyond two hops, owing to the limited performance of one-step methods and the failure of two-step methods when selecting irrelevant passages in earlier stages. In this work, we introduce Beam Retrieval, a general end-to-end retrieval framework for multi-hop QA. This approach maintains multiple partial hypotheses of relevant passages at each step, expanding the search space and reducing the risk of missing relevant passages. Moreover, Beam Retrieval jointly optimizes an encoder and two classification heads by minimizing the combined loss across all hops. To establish a complete QA system, we incorporate a supervised reader or a zero-shot GPT-3.5. Experimental results demonstrate that Beam Retrieval achieves a nearly 50% improvement compared with baselines on challenging MuSiQue-Ans, and it also surpasses all previous retrievers on HotpotQA and 2WikiMultiHopQA. Providing high-quality context, Beam Retrieval helps our supervised reader achieve new state-of-the-art performance and substantially improves (up to 28.8 points) the QA performance of zero-shot GPT-3.5.Comment: Code is available at https://github.com/canghongjian/beam_retrieve

Effect of astigmatism on visual outcomes after multifocal intraocular lens implantation: a systematic review and meta-analysis

PurposeTo investigate the effects of postoperative astigmatism on the visual outcomes following presbyopia-correcting surgery with multifocal intraocular lens implantation.MethodsA comprehensive literature search was conducted using PubMed, Embase, and Web of Science for articles published until January 2023. Additionally, we included retrospective case series and prospective comparative studies. The combined mean difference (MD) with 95% confidence intervals (CI) and odds ratio (OR) with 95% CI were used to express continuous and categorical outcomes, respectively. All statistical analyses were performed using Review Manager (version 5.4.1).ResultsWe included nine eligible studies that analyzed 3,088 eyes. The proportion of eyes with useful postoperative visual acuity (logMAR ≤ 0.20) and residual astigmatism significantly differed with respect to the magnitude of astigmatism and presence/absence of blurred vision (p < 0.001 for both). Additionally, the mean uncorrected distance visual acuity (MD, 0.14; 95% CI, 0.06 to 0.21; p = 0.0003) and uncorrected intermediate visual acuity (MD, 0.07; 95% CI, 0.00 to 0.13; p = 0.04), but not the uncorrected near visual acuity (MD, 0.02; 95%CI-0.01 to 0.05; p = 0.17), significantly differed according to the magnitude of astigmatism.ConclusionAstigmatism, even at low levels (≥ 0.5D), has a significant effect on visual outcomes, especially on UDVA and UIVA, following multifocal intraocular lens implantation. Accurate preoperative and postoperative evaluation of astigmatism is important

WonderFlow: Narration-Centric Design of Animated Data Videos

Creating an animated data video enriched with audio narration takes a significant amount of time and effort and requires expertise. Users not only need to design complex animations, but also turn written text scripts into audio narrations and synchronize visual changes with the narrations. This paper presents WonderFlow, an interactive authoring tool, that facilitates narration-centric design of animated data videos. WonderFlow allows authors to easily specify a semantic link between text and the corresponding chart elements. Then it automatically generates audio narration by leveraging text-to-speech techniques and aligns the narration with an animation. WonderFlow provides a visualization structure-aware animation library designed to ease chart animation creation, enabling authors to apply pre-designed animation effects to common visualization components. It also allows authors to preview and iteratively refine their data videos in a unified system, without having to switch between different creation tools. To evaluate WonderFlow's effectiveness and usability, we created an example gallery and conducted a user study and expert interviews. The results demonstrated that WonderFlow is easy to use and simplifies the creation of data videos with narration-animation interplay

A Schistosoma japonicum chimeric protein with a novel adjuvant induced a polarized Th1 immune response and protection against liver egg burdens

<p>Abstract</p> <p>Background</p> <p>Schitosomiasis japonica is still a significant public health problem in China. A protective vaccine for human or animal use represents an important strategy for long-term control of this disease. Due to the complex life cycle of schistosomes, different vaccine design approaches may be necessary, including polyvalent subunit vaccines. In this study, we constructed four chimeric proteins (designated SjGP-1~4) via fusion of Sj26GST and four individual paramyosin fragments. We tested these four proteins as vaccine candidates, and investigated the effect of deviating immune response on protection roles in mice.</p> <p>Methods</p> <p>The immunogencity and protection efficacy of chimeric proteins were evaluated in mice. Next, the chimeric protein SjGP-3 was selected and formulated in various adjuvants, including CFA, ISA 206, IMS 1312 and ISA 70M. The titers of antigen-specific IgG, IgE and IgG subclass were measured. The effect of adjuvant on cytokine production and percentages of CD3⁺CD8^-IFN-γ⁺cells and CD3⁺CD8^-IL-4⁺cells were analyzed at different time points. Worm burdens and liver egg counts in different adjuvant groups were counted to evaluate the protection efficacy against cercarial challenge.</p> <p>Results</p> <p>Immunization of mice with chimeric proteins provided various levels of protection. Among the four proteins, SjGP-3 induced the highest level of protection, and showed enhanced protective efficacy compared with its individual component Sj26GST. Because of this, SjGP-3 was further formulated in various adjuvants to investigate the effect of adjuvant on immune deviation. The results revealed that SjGP-3 formulated in veterinary adjuvant ISA 70M induced a lasting polarized Th1 immune response, whereas the other adjuvants, including CFA, ISA 206 and IMS 1312, generated a moderate mixed Th1/Th2 response after immunization but all except for IMS 1312 shifted to Th2 response after onset of eggs. More importantly, the SjGP-3/70M formulation induced a significant reduction in liver egg deposition at 47.0–50.3% and the number of liver eggs per female at 34.5–37.2% but less effect on worm burdens at only 17.3–23.1%, whereas no effect of the formulations with other adjuvants on the number of liver eggs per female was observed.</p> <p>Conclusion</p> <p>Construction of polyvalent subunit vaccine was capable to enhance immunogenicity and protection efficacy against schistosomiasis. There was correlation of the polarized Th1 response with reduction of liver egg burdens, supporting the immune deviation strategy for schistosomiasis japonica vaccine development.</p

Self-partitioning SlipChip for slip-induced droplet formation and human papillomavirus viral load quantification with digital LAMP

Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide, and persistent HPV infection can cause warts and even cancer. Nucleic acid analysis of HPV viral DNA can be very informative for the diagnosis and monitoring of HPV. Digital nucleic acid analysis, such as digital PCR and digital isothermal amplification, can provide sensitive detection and precise quantification of target nucleic acids, and its utility has been demonstrated in many biological research and medical diagnostic applications. A variety of methods have been developed for the generation of a large number of individual reaction partitions, a key requirement for digital nucleic acid analysis. However, an easily assembled and operated device for robust droplet formation without preprocessing devices, auxiliary instrumentation or control systems is still highly desired. In this paper, we present a self-partitioning SlipChip (sp-SlipChip) microfluidic device for the slip-induced generation of droplets to perform digital loop-mediated isothermal amplification (LAMP) for the detection and quantification of HPV DNA. In contrast to traditional SlipChip methods, which require the precise alignment of microfeatures, this sp-SlipChip utilized a design of “chain-of-pearls” continuous microfluidic channel that is independent of the overlapping of microfeatures on different plates to establish the fluidic path for reagent loading. Initiated by a simple slipping step, the aqueous solution can robustly self-partition into individual droplets by capillary pressure-driven flow. This advantage makes the sp-SlipChip very appealing for the point-of-care quantitative analysis of viral load. As a proof of concept, we performed digital LAMP on an sp-SlipChip to quantify human papillomaviruses (HPVs) 16 and 18 and tested this method with fifteen anonymous clinical samples

Cloning and sequence analysis of Wild Argali short palate, lung and nasal epithelium clone 1 cDNA

Objective Experiments were conducted to clone the sequence of Wild Argali short palate, lung and nasal epithelium clone 1 (SPLUNC1) cDNA, and to lay the foundation for further study the biological function of Wild Argali SPLUNC1. Methods The complete sequence of Wild Argali SPLUNC1 cDNA was generated by rapid amplification of cDNA ends. The entire coding sequence was inserted into the pPIC9K vector and expressed in Pichia pastoris (P. pastoris) GS115. The recombinant SPLUNC1 protein was detected by Western blot and purified by Ni2+ chelate affinity chromatography. The test of effect of the protein on Mycoplasma ovipneumoniae (MO) was performed with real-time polymerase chain reaction. Results The Wild Argali SPLUNC1 cDNA was 1,076 bp with an open reading frame of 768 bp, which encoded a 26.49 kDa protein composed of 255 amino acids. Its amino acid sequence shared 98.4%, 96.9%, 94.5%, 90.2%, 80.8%, 78.4%, 78.3%, 72.5%, 72.3%, 68.8% identity with those of SPLUNC1 cDNA from Ovis aries (accession no. NP_001288334.1), Capra hircus (accession no. XP_005688516.1), Pantholops hodgsonii (accession no. XP_005979709.1), Bos taurus (accession no. NP_776851.1), Felis catus (accession no. XP_006929910.1), Homo sapiens (accession no. NP_001230122.1), Sus scrofa (accession no. NP_001005727.1), Chinchilla lanigera (accession no. NP_001269294.1), Mus musculus (accession no. NP_035256.2), and Rattus norvegicus (accession no. NP_742028.1), respectively. The recombinant protein corresponded to the expected molecular mass of 25.47 kDa as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it was detected in the supernatant of P. pastoris, and it could be purified. The results from the test of inhibition effect of argali recombinant SPLUNC1 protein on MO showed that the product could inhibit MO very well (p<0.01). Conclusion The amino acid sequence of Wild Argali SPLUNC1 was different from other organisms. The recombinant SPLUNC1 protein has good biological activity

Research progress of sophoridine’s pharmacological activities and its molecular mechanism: an updated review

Background: Sophoridine, the major active constituent of Sophora alopecuroides and its roots, is a bioactive alkaloid with a wide range of pharmacological effects, including antitumor, anti-inflammatory, antiviral, antibacterial, analgesic, cardioprotective, and immunoprotective activities. Sophora flavescens Aiton is a traditional Chinese medicine that is bitter and cold. Additionally, it also exhibits the effects of clearing heat, eliminating dampness, and expelling insects.Aims of the study: To summarize the pharmacological research and associated mechanisms of sophoridine, we compiled this review by combining a huge body of relevant literature.Materials and methods: The information related to this article was systematically collected from the scientific literature databases including PubMed, Google Scholar, Web of Science, Science Direct, Springer, China National Knowledge Infrastructure, published books, PhD and MS dissertations.Results: Its antitumor activity is particularly remarkable, as it can inhibit cancer cell proliferation, invasion, and metastasis while inducing cell cycle arrest and apoptosis. Additionally, sophoridine also holds therapeutic potential for myocardial ischemia, osteoporosis, arrhythmias, and neurological disorders, primarily through the suppression of related inflammatory factors and cell apoptosis. However, sophoridine has also exhibited adverse effects such as hepatotoxicity and neurotoxicity. The antidisease effect and mechanism of sophoridine are diverse, so it has high research value.Conclusion: As an important traditional Chinese medicine alkaloid, modern pharmacological studies have demonstrated that sophoridine has prominent bioactivities, especially on anti-tumor anti-inflammation activities, and cardiovascular system protection. These activities provide prospects for novel drug development for cancer and some chronic diseases. Nevertheless, the understanding of the multitarget network pharmacology, long-term in vivo toxicity, and clinical efficacy of sophoridine require further detailed research