Trustworthy assertion classification through prompting.

Accurate identification of the presence, absence or possibility of relevant entities in clinical notes is important for healthcare professionals to quickly understand crucial clinical information. This introduces the task of assertion classification - to correctly identify the assertion status of an entity in the unstructured clinical notes. Recent rule-based and machine-learning approaches suffer from labor-intensive pattern engineering and severe class bias toward majority classes. To solve this problem, in this study, we propose a prompt-based learning approach, which treats the assertion classification task as a masked language auto-completion problem. We evaluated the model on six datasets. Our prompt-based method achieved a micro-averaged F-1 of 0.954 on the i2b2 2010 assertion dataset, with ∼1.8% improvements over previous works. In particular, our model showed excellence in detecting classes with few instances (few-shot). Evaluations on five external datasets showcase the outstanding generalizability of the prompt-based method to unseen data. To examine the rationality of our model, we further introduced two rationale faithfulness metrics: comprehensiveness and sufficiency. The results reveal that compared to the "pre-train, fine-tune" procedure, our prompt-based model has a stronger capability of identifying the comprehensive (∼63.93%) and sufficient (∼11.75%) linguistic features from free text. We further evaluated the model-agnostic explanations using LIME. The results imply a better rationale agreement between our model and human beings (∼71.93% in average F-1), which demonstrates the superior trustworthiness of our model.

AoStuA, an APSES transcription factor, regulates the conidiation, trap formation, stress resistance and pathogenicity of the nematode-trapping fungus Arthrobotrys oligospora.

The APSES protein family comprises a conserved class of fungus-specific transcriptional regulators. Some members have been identified in partial ascomycetes. In this study, the APSES protein StuA (AoStuA) of the nematode-trapping fungus Arthrobotrys oligospora was characterized. Compared with the wild-type (WT) strain, three ΔAoStuA mutants grew relatively slowly, displayed a 96% reduction in sporulation capacity and a delay in conidial germination. The reduced sporulation capacity correlated with transcriptional repression of several sporulation-related genes. The mutants were also more sensitive to chemical stressors than the WT strain. Importantly, the mutants were unable to produce mycelial traps for nematode predation. Moreover, peroxisomes and Woronin bodies were abundant in the WT cells but hardly found in the cells of those mutants. The lack of such organelles correlated with transcriptional repression of some genes involved in the biogenesis of peroxisomes and Woronin bodies. The transcript levels of several genes involved in the cAMP/PKA signalling pathway were also significantly reduced in the mutants versus the WT strain, implicating a regulatory role of AoStuA in the transcription of genes involved in the cAMP/PKA signalling pathway that regulates an array of cellular processes and events. In particular, AoStuA is indispensable for A. oligospora trap formation and virulence.

Regulation of nonylphenol-induced reproductive toxicity in mouse spermatogonia cells by miR-361-3p.

Nonylphenol (NP) is an environmental chemical that affects apoptosis and male infertility. In our study, we found that a high concentration of NP could down-regulate the expression of microRNA-361-3p (miR-361-3p) in the murine GC-1 spermatogonia cell line and in vivo in murine spermatogonia. Additionally, one direct target of this miR, the 3' untranslated region of Killin (Klln) mRNA, was identified. Klln encodes a transcription factor that directly regulates the expression of Tp73 (transcriptionally active p73), whose encoded protein can up-regulate the expression of Puma (p53 upregulated modulator of apoptosis). Thus, our investigation revealed that the expression of Klln, Tp73, and Puma increased upon NP-dependent down-regulation of miR-361-3p, which eventually leads to apoptosis of spermatogonia.

Brucella melitensis M5-90Δbp26 as a potential live vaccine that allows for the distinction between natural infection and immunization.

Brucella is Gram-negative intracellular bacterial pathogen that infects humans and animals and contributes to great economic losses in developing countries. Presently, live attenuated Brucella vaccines (Brucella melitensis M5-90) are the most effective means of brucellosis control and prevention in animals. However, these vaccines have several drawbacks, such as an inability to distinguish between a natural infection and immunization and an association with abortions in pregnant animals. Therefore, this study constructed a Brucella M5-90Δbp26 mutant and evaluated its virulence. The survival of the M5-90Δbp26 mutant was attenuated in human placenta trophoblastic 8 cells (HPT-8 cells) and in BALB/c mice, with a high immunoprotectivity noted in mice. Furthermore, safety tests showed that the M5-90Δbp26 mutant was less virulent than the M5-90 vaccine strain. Additionally, an indirect enzyme-linked immunosorbent assay (ELISA) screening was shown to detect the presence of Brucella protein 26 (BP26) with high sensitivity, with M5-90Δbp26 inoculation accompanied with a lack of BP26 expression, and was further confirmed by western blotting. Together, the M5-90Δbp26 mutant and the indirect ELISA can be employed to distinguish vaccinated livestock from infected animals.

Clinical utility of three-dimensional echocardiography in the evaluation of tricuspid regurgitation induced by implantable device leads.

OBJECTIVES: Implantable device leads could cause tricuspid regurgitation (TR) by interfering with leaflet motion. This study evaluated the feasibility of using three-dimensional transthoracic echocardiography (3DTTE) to identify lead-induced tricuspid regurgitation (LITR). METHODS: 3DTTE full-volume images of the right ventricle (RV) and zoomed images of the tricuspid valve were obtained in 207 patients with implanted devices, and the images were analyzed. TR severity was estimated based on measurements of the proximal isovelocity surface area (PISA) radius. RESULTS: 3DTTE clearly identified the course and position of the leads in 74% of the patients. The lead tips were located in the RV apex or outflow tract in 95% of patients and in the interventricular septum (IVS) in 5% of patients. At the tricuspid annular level, 25% of leads were impinging on a leaflet, 41% were located in the commissure of two leaflets, and 34% were in the middle of the tricuspid orifice. 3D images revealed that when the lead tip was in the IVS or the lead was impinging on a leaflet, the device lead was more likely to interfere with leaflet mobility (P<.05). Interfering leads were associated with more significant TR than noninterfering leads (P<.05). CONCLUSIONS: 3DTTE showed a clear association between lead interference and TR worsening after lead placement. 3DTTE guidance should be considered for the placement of leads.

Precision Measurement for Metastable Helium Atoms of the 413 nm Tune-Out Wavelength at Which the Atomic Polarizability Vanishes.

We present the first measurement for helium atoms of the tune-out wavelength at which the atomic polarizability vanishes. We utilize a novel, highly sensitive technique for precisely measuring the effect of variations in the trapping potential of confined metastable (2^{3}S_{1}) helium atoms illuminated by a perturbing laser light field. The measured tune-out wavelength of 413.0938(9_{stat})(20_{syst}) nm compares well with the value predicted by a theoretical calculation [413.02(9) nm] which is sensitive to finite nuclear mass, relativistic, and quantum electrodynamic effects. This provides motivation for more detailed theoretical investigations to test quantum electrodynamics.

Solution of the Dirac Coulomb equation for helium-like ions in the Poet-Temkin model.

The Dirac-Coulomb equation for the helium atom is studied under the restrictions of the Poet-Temkin model which replaces the 1/r12 interaction by the simplified 1/r> form. The effective reduction in the dimensionality made it possible to obtain binding energies for the singlet and triplet states in this model problem with a relative precision from 10(-8) to 10(-10). The energies for the singlet state were consistent with a previous configuration interaction calculation [H. Tatewaki and Y. Watanabe, Chem. Phys. 389, 58 (2011)]. Manifestations of Brown-Ravenhall disease were noted at higher values of nuclear charge and ultimately limited the accuracy of the Poet-Temkin model energy. The energies from a no-pair configuration interaction (CI) calculation (the negative-energy states for the appropriate hydrogen-like ion were excluded from the CI expansion) were found to be different from the unrestricted B-spline calculation.

Effects of gross total resection and subtotal resection on survival outcomes of glioma patients: a meta-analysis.

This study was to conduct a meta-analysis to explore the impact of gross total resection (GTR) and subtotal resection (STR) on survival outcomes in glioma patients. Relevant studies were searched in multiple databases from the available date of inception through 30 December 2021. The weighted mean differences (WMDs), relative risks (RRs), or hazard ratios (HRs) with 95% confidence intervals (CIs) were used to access the effect of GTR versus STR treatments on the outcomes. The histology (low-grade or high-grade) and study population (children and adults) were used for subgroup analysis. Sensitivity analysis was performed for all outcomes. Begg's test and trim-and-fill method were used for publication bias. Totally 100 studies enrolling 62,129 patients were selected in this meta-analysis. The summary results showed that GTR was superior in improving 1-, 2-, 3-, 5-, 10-, 15-year overall survival (OS), OS time, 1-, 3-, 5-year progression-free survival (PFS), recurrence, local control and seizure control among glioma patients. In addition, high-grade patients who underwent GTR had improvements in 1-, 2- and 3-year OS, OS time, and 1-year PFS, while low-grade patients receiving GTR had improvements in 2-, 5- and 15-year OS, recurrence, seizure control, and tumor progression compared with those receiving STR. GTR was likely to be more effective on survival outcomes than STR among patients with gliomas.

The effect of aminolevulinic acid hydrochloride topical powder photodynamic therapy versus nocardia rubra cell wall skeleton and observers group in the treatment of cervical low-grade squamous intraepithelial lesions with human papillomavirus infection: A non-randomized study, controlled pilot study.

There are insufficient studies comparing the efficacy of aminolevulinic acid hydrochloride topical powder (ALA) photodynamic therapy (PDT) against Nocardia rubra cell wall skeleton (Nr-CWS) therapy in the treatment of cervical low-grade squamous intraepithelial lesion (LSIL) with human papillomavirus (HPV), especially for long-term efficacy. Patients with cervical LSIL and HPV infection were divided into 3 treatment groups based on their own choice. All patients had a follow-up test including HPV testing, cytology and colposcopy at 4 to 6 months and 12 months after the treatment. Among142 patients, patients received 51 ALA PDT and 41 patients received Nr-CWS. Another 50 patients who refused treatment were included in the Observers group. Four to six months or 12 months after treatment, there was significant difference between 3 groups in the clearance rate of HR-HPV infection and the complete remission (CR) rates of cervical LSIL; the CR rates of cervical LSIL in the ALA PDT group was significantly higher than the Nr-CWS group; but there was no significant difference between 2 groups in the clearance rate of HPV infection. The CR rates of cervical LSIL and the clearance rate of HPV infection in the ALA PDT group was significantly higher than the Observers group; the CR rates of cervical LSIL and the clearance rate of HPV infection in the Nr-CWS group was significantly higher than the Observers group; there was no significant difference in the recurrence rates in ALA PDT and Nr-CWS group after 12 months. Both of ALA PDT and Nr-CWS group had lower recurrence rate than the Observers group. The effect of ALA PDT is similar to Nr-CWS in the clearance rate of HR-HPV infection. Compared to the Nr-CWS group, the CR rates of cervical LSIL were considerably greater in the ALA PDT group. The effect of ALA PDT in the clearance rate of HPV infection and CR rates of cervical LSIL was significantly higher than the follow-up group; Both of ALA PDT and Nr-CWS group had lower recurrence rate than the Observers group. For cervical LSIL with HPV infection, ALA PDT is a very successful therapeutic method that is noninvasive.

Comparative effect of stenting plus medical therapy vs medical therapy alone on the risk of stroke and death in patients with symptomatic intracranial stenosis: a systematic review and meta-analysis.

BACKGROUND: Recently, several randomized controlled trials (RCTs) of stenting plus medical therapy versus medical therapy alone have been successfully conducted for the treatment of patients with symptomatic intracranial stenosis. This study aimed to evaluate differences between these two therapies in the risk of stroke and death. METHODS: MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before August 24, 2022. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) was analysed and calculated with a random effect model or a fixed effects model. RESULTS: We pooled 921 participants from three RCTs. Compared to the medical therapy alone group, the stenting plus medical therapy group had a higher risk of 30-day death or stroke (RR = 2.69 [1.64-4.41], P < 0.0001, I2 = 0%). When the follow-up period exceeded 1 year (≥ 1 year), there was no significant difference in the risk of stroke or death between these two groups. The subgroup analysis showed that if the time from stroke onset to implantation was extended, additional stenting would have no effect on the risk of stroke or death, whether within 30 days or within 1 year (P = 0.16 and 0.78). CONCLUSION: Medical therapy alone has a lower risk of stroke and death in the short term than stenting plus medical therapy, while no difference exists in the long term. More studies are still needed to further explore the precision strategy of stent implantation for symptomatic intracranial stenosis patients.

Less Likely Brainstorming: Using Language Models to Generate Alternative Hypotheses.

A human decision-maker benefits the most from an AI assistant that corrects for their biases. For problems such as generating interpretation of a radiology report given findings, a system predicting only highly likely outcomes may be less useful, where such outcomes are already obvious to the user. To alleviate biases in human decision-making, it is worth considering a broad differential diagnosis, going beyond the most likely options. We introduce a new task, "less likely brainstorming," that asks a model to generate outputs that humans think are relevant but less likely to happen. We explore the task in two settings: a brain MRI interpretation generation setting and an everyday commonsense reasoning setting. We found that a baseline approach of training with less likely hypotheses as targets generates outputs that humans evaluate as either likely or irrelevant nearly half of the time; standard MLE training is not effective. To tackle this problem, we propose a controlled text generation method that uses a novel contrastive learning strategy to encourage models to differentiate between generating likely and less likely outputs according to humans. We compare our method with several state-of-the-art controlled text generation models via automatic and human evaluations and show that our models' capability of generating less likely outputs is improved.

Effects of dietary restriction on genome stability are sex and feeding regimen dependent.

Preserving genome stability is essential to prevent aging and cancer. Dietary restriction (DR) is the most reproducible non-pharmacological way to improve health and extend lifespan in various species. Whether DR helps to preserve genome stability and whether this effect is altered by experimental variables remain unclear. Moreover, DR research relies heavily on experimental animals, making the development of reliable in vitro mimetics of great interest. Therefore, we tested the effects of sex and feeding regimen (time-restricted eating, alternate day fasting and calorie restriction) on genome stability in CF-1 mice and whether these effects can be recapitulated by cell culture paradigms. Here, we show that calorie restriction significantly decreases the spontaneous micronuclei (MN), a biomarker of genome instability, in bone marrow cells of females instead of males. Alternate day fasting significantly decreases cisplatin-induced MN in females instead of males. Unexpectedly, daily time-restricted eating significantly exacerbates cisplatin-induced MN in males but not in females. Additionally, we design several culture paradigms that are able to faithfully recapitulate the key effects of these DR regimens on genome stability. In particular, 30% reduction of serum, a mimetic of calorie restriction, exhibits a strong ability to decrease spontaneous and cisplatin-induced MN in immortalized human umbilical vein endothelial cells. We conclude that the effects of different DR regimens on genome stability are not universal and females from each diet regimen sustain a more stable genome than males. Our results provide novel insight into the understanding of how DR influences genome stability in a sex and regimen dependent way, and suggest that our in vitro DR mimetics could be adopted to study the underlying molecular mechanisms.

A glycosylation-related gene signature predicts prognosis, immune microenvironment infiltration, and drug sensitivity in glioma.

Glioma represents the most common primary cancer of the central nervous system in adults. Glycosylation is a prevalent post-translational modification that occurs in eukaryotic cells, leading to a wide array of modifications on proteins. We obtained the clinical information, bulk RNA-seq data, and single-cell RNA sequencing (scRNA-seq) from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gene Expression Omnibus (GEO), and Repository of Molecular Brain Neoplasia Data (Rembrandt) databases. RNA sequencing data for normal brain tissues were accessed from the Genotype-Tissue Expression (GTEx) database. Then, the glycosylation genes that were differentially expressed were identified and further subjected to variable selection using a least absolute shrinkage and selection operator (LASSO)-regularized Cox model. We further conducted enrichment analysis, qPCR, nomogram, and single-cell transcriptome to detect the glycosylation signature. Drug sensitivity analysis was also conducted. A five-gene glycosylation signature (CHPF2, PYGL, GALNT13, EXT2, and COLGALT2) classified patients into low- or high-risk groups. Survival analysis, qPCR, ROC curves, and stratified analysis revealed worse outcomes in the high-risk group. Furthermore, GSEA and immune infiltration analysis indicated that the glycosylation signature has the potential to predict the immune response in glioma. In addition, four drugs (crizotinib, lapatinib, nilotinib, and topotecan) showed different responses between the two risk groups. Glioma cells had been classified into seven lines based on single-cell expression profiles. The five-gene glycosylation signature can accurately predict the prognosis of glioma and may offer additional guidance for immunotherapy.

Evaluating large language models on medical evidence summarization.

Recent advances in large language models (LLMs) have demonstrated remarkable successes in zero- and few-shot performance on various downstream tasks, paving the way for applications in high-stakes domains. In this study, we systematically examine the capabilities and limitations of LLMs, specifically GPT-3.5 and ChatGPT, in performing zero-shot medical evidence summarization across six clinical domains. We conduct both automatic and human evaluations, covering several dimensions of summary quality. Our study demonstrates that automatic metrics often do not strongly correlate with the quality of summaries. Furthermore, informed by our human evaluations, we define a terminology of error types for medical evidence summarization. Our findings reveal that LLMs could be susceptible to generating factually inconsistent summaries and making overly convincing or uncertain statements, leading to potential harm due to misinformation. Moreover, we find that models struggle to identify the salient information and are more error-prone when summarizing over longer textual contexts.

Evaluating Large Language Models on Medical Evidence Summarization.

Recent advances in large language models (LLMs) have demonstrated remarkable successes in zero- and few-shot performance on various downstream tasks, paving the way for applications in high-stakes domains. In this study, we systematically examine the capabilities and limitations of LLMs, specifically GPT-3.5 and ChatGPT, in performing zero-shot medical evidence summarization across six clinical domains. We conduct both automatic and human evaluations, covering several dimensions of summary quality. Our study has demonstrated that automatic metrics often do not strongly correlate with the quality of summaries. Furthermore, informed by our human evaluations, we define a terminology of error types for medical evidence summarization. Our findings reveal that LLMs could be susceptible to generating factually inconsistent summaries and making overly convincing or uncertain statements, leading to potential harm due to misinformation. Moreover, we find that models struggle to identify the salient information and are more error-prone when summarizing over longer textual contexts.

Convergence of the multipole expansions of the polarization and dispersion interactions for atoms under confinement.

The multipole expansion of the polarization interaction between a charged particle and an electrically neutral object has long been known to be asymptotic in nature, i.e., the multiple expansion diverges at any finite distance from the atom. However, the multipole expansion of the polarization potential of a confined hydrogen atom is shown to be absolutely convergent at a distance outside the confinement radius, R(0), of the atom. The multipole expansion of the dispersion potential between two confined hydrogen atoms is also shown to be absolutely convergent provided the two atoms satisfy R > 2R(0), where R is the inter-nuclear separation. These results were established analytically using oscillator strength sum rules and verified numerically using a B-spline description of the hydrogen ground state and its excitation spectrum.

The long-range non-additive three-body dispersion interactions for the rare gases, alkali, and alkaline-earth atoms.

The long-range non-additive three-body dispersion interaction coefficients Z(111), Z(112), Z(113), and Z(122) are computed for many atomic combinations using standard expressions. The atoms considered include hydrogen, the rare gases, the alkali atoms (up to Rb), and the alkaline-earth atoms (up to Sr). The term Z(111) arising from three mutual dipole interactions is known as the Axilrod-Teller-Muto coefficient or the DDD (dipole-dipole-dipole) coefficient. Similarly, the terms Z(112), Z(113), and Z(122) arise from the mutual combinations of dipole (1), quadrupole (2), and octupole (3) interactions between atoms and they are sometimes known, respectively, as dipole-dipole-quadrupole, dipole-dipole-octupole, and dipole-quadrupole-quadrupole coefficients. Results for the four Z coefficients are given for the homonuclear trimers, for the trimers involving two like-rare-gas atoms, and for the trimers with all combinations of the H, He, and Li atoms. An exhaustive compilation of all coefficients between all possible atomic combinations is presented as supplementary data.

Oscillator strengths between low-lying ro-vibrational states of hydrogen molecular ions.

It is important for experimental design to know the transition oscillator strengths in hydrogen molecular ions. In this work, for HD(+), HT(+), and DT(+), we calculate the ro-vibrational energies and oscillator strengths of dipole transitions between two ro-vibrational states with the vibrational quantum number ν = 0-5 and the total angular momentum L = 0-5. The oscillator strengths of HT(+) and DT(+) are presented as supplementary material.

EchoGen: A New Benchmark Study on Generating Conclusions from Echocardiogram Notes.

Generating a summary from findings has been recently explored (Zhang et al., 2018, 2020) in note types such as radiology reports that typically have short length. In this work, we focus on echocardiogram notes that is longer and more complex compared to previous note types. We formally define the task of echocardiography conclusion generation (EchoGen) as generating a conclusion given the findings section, with emphasis on key cardiac findings. To promote the development of EchoGen methods, we present a new benchmark, which consists of two datasets collected from two hospitals. We further compare both standard and state-of-the-art methods on this new benchmark, with an emphasis on factual consistency. To accomplish this, we develop a tool to automatically extract concept-attribute tuples from the text. We then propose an evaluation metric, FactComp, to compare concept-attribute tuples between the human reference and generated conclusions. Both automatic and human evaluations show that there is still a significant gap between human-written and machine-generated conclusions on echo reports in terms of factuality and overall quality.