Epilepsy as a Novel Phenotype of BPTF-Related Disorders.

BACKGROUND: Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) is associated to BPTF gene haploinsufficiency. Epilepsy was not included in the initial descriptions of NEDDFL, but emerging evidence indicates that epileptic seizures occur in some affected individuals. This study aims to investigate the electroclinical epilepsy features in individuals with NEDDFL. METHODS: We enrolled individuals with BPTF-related seizures or interictal epileptiform discharges (IEDs) on electroencephalography (EEG). Demographic, clinical, genetic, raw EEG, and neuroimaging data as well as response to antiseizure medication were assessed. RESULTS: We studied 11 individuals with a null variant in BPTF, including five previously unpublished ones. Median age at last observation was 9 years (range: 4 to 43 years). Eight individuals had epilepsy, one had a single unprovoked seizure, and two showed IEDs only. Key features included (1) early childhood epilepsy onset (median 4 years, range: 10 months to 7 years), (2) well-organized EEG background (all cases) and brief bursts of spikes and slow waves (50% of individuals), and (3) developmental delay preceding seizure onset. Spectrum of epilepsy severity varied from drug-resistant epilepsy (27%) to isolated IEDs without seizures (18%). Levetiracetam was widely used and reduced seizure frequency in 67% of the cases. CONCLUSIONS: Our study provides the first characterization of BPTF-related epilepsy. Early-childhood-onset epilepsy occurs in 19% of subjects, all presenting with a well-organized EEG background associated with generalized interictal epileptiform abnormalities in half of these cases. Drug resistance is rare.

Different dosage forms of GnRHa with endocrine therapy in premenopausal hormone Receptor-Positive breast cancer.

BACKGROUND: Despite the wide use of a three-month gonadotropin-releasing hormone agonist (3M GnRHa) for ovarian function suppression (OFS) in premenopausal breast cancer patients, it remains unclear whether it is as effective and safe as a one-month GnRHa regimen (1M GnRHa) when combined with selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs), especially in younger patients. METHODS: This retrospective cohort study included 1109 premenopausal hormone receptor-positive (HR+) breast cancer patients treated with GnRHa plus SERM or AI. The estradiol (E2) inhibition rate within 1-24 months after treatment with 1M or 3M GnRHa in cohorts and different subgroups was analyzed. RESULTS: Following 1:1 propensity score matching, 950 patients with a mean age of 39 years and a median follow-up of 46 months were included. Both the 1M and 3M groups achieved >90% E2 inhibition within 24 months (94.53% vs 92.84%, 95% CI (-4.78%, 1.41%)), confirming the non-inferiority of 3M GnRHa. Both 1M and 3M GnRHa rapidly and consistently reduced E2 levels. 60 (6.3%) patients experienced incomplete ovarian function suppression (iOFS), with similar rates in the 1M and 3M groups (5.5% vs 7.2%). iOFS mainly occurred within the first 12 months, with age <40 years and no prior chemotherapy being the risk factors. Similar disease-free survival (DFS) and overall survival (OS) were found in the 1M and 3M groups, and in patients with complete and incomplete OFS (p > .05). CONCLUSIONS: The OFS with 3M GnRHa was not inferior to that with 1M GnRHa, regardless of age or combination with a SERM or an AI.

Development and validation of a nomogram for predicting the occurrence of renal dysfunction after treatment of immune checkpoint inhibitor: a retrospective case-control study.

PURPOSE: The administration of immune checkpoint inhibitors (ICIs) may lead to renal adverse events, notably including renal dysfunction. To early predict the probability of renal dysfunction after ICIs therapy, a retrospective case-control study was conducted. METHODS: Clinical information on ICIs-treated patients was collected. Multivariable logistic regression was applied to identify risk factors for renal dysfunction after ICIs treatment. Moreover, a nomogram model was developed and validated internally. RESULTS: A total of 442 patients were included, among which 35 (7.9%) experienced renal dysfunction after ICIs treatment. Lower baseline estimated glomerular filtration rate (eGFR) (OR 0.941; 95% CI 0.917 to 0.966; p<0.001), concurrent exposure of platinum(OR 4.014; 95% CI 1.557 to 10.346; p=0.004), comorbidities of hypertension (OR 3.478; 95% CI 1.600 to 7.562; p=0.002) and infection (OR 5.402; 95% CI 1.544 to 18.904; p=0.008) were found to be independent associated with renal dysfunction after ICIs treatment. To develop a predictive nomogram for the occurrence of renal dysfunction after ICIs treatment, the included cases were divided into training and validation groups in a ratio of 7:3 randomly. The above four independent risk factors were included in the model. The area under the receiver operating characteristic curves of the predictiive model were 0.822 (0.723-0.922) and 0.815 (0.699-0.930) in the training and validation groups, respectively. CONCLUSIONS: Lower baseline eGFR, platinum exposure, comorbidities of hypertension and infection were predictors of renal dysfunction in ICIs-treated patients with cancer. A nomogram was developed to predict the probability of renal dysfunction after ICIs treatment, which might be operable and valuable in clinical practice.

Effects of Advance Care Planning on End-of-Life Indicators for Nursing Home Residents-An Experimental Study with a Retrospective Chart Review.

Advance care planning (ACP) has the potential to improve the outcomes of end-of-life care for residents in nursing homes. The aim of this study was to determine whether an ACP program was beneficial for nursing home residents by assessing end-of-life indicators. An experimental study with a retrospective chart review was conducted. In total, 37 residents in the intervention group participated in an institutional advance care planning program for 1 year, and their chart data over 1 year were collected following the completion of the program; 33 residents in the control group had died within 1 year before the start date of program, and their chart data were reviewed retrospectively. Chi-square and t tests were used to examine four indicators of the quality of end-of-life care. Compared with the control group, the intervention group had a higher proportion of do-not-resuscitate directives, hospice care before death, and deaths in the nursing home, and fewer hospitalizations and deaths in an emergency department. ACP programs may improve the quality of end-of-life care for nursing home residents in Taiwan. Further research across different long-term care facilities is warranted.

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase II single-arm study.

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin (PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (BC). Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD (30-35 mg/m2) and cyclophosphamide (600 mg/m2), followed by four cycles of taxanes (docetaxel, 90-100 mg/m2 or nab-paclitaxel, 260 mg/m2), concomitant with eight cycles of trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0). Secondary endpoints included breast pCR (bpCR), objective response rate (ORR), disease control rate, rate of breast-conserving surgery (BCS), and safety (with a focus on cardiotoxicity). Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42 (53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval (95% CI), 48.5%-71.2%] patients achieved tpCR, and 49 (62.8%) achieved bpCR. ORRs were 76.9% (95% CI, 66.0%-85.7%) and 93.6% (95% CI, 85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine (11.5%) patients experienced asymptomatic left ventricular ejection fraction (LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP (NT-proBNP), troponin I, or high-sensitivity troponin. Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile, especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

Comparing the effect of assessment-simulation-animation-based against traditional education on nursing students' anxiety and self-efficacy in maternity clinical practicum.

BACKGROUND: The clinical practicum is the practical course that causes the most anxiety in nursing undergraduates. Although high-fidelity simulation education has been demonstrated to boost nursing students' self-efficacy and decrease anxiety in patient care, it is also associated with excessive psychological stress. Assessment-simulation-animation-based (ASA-based) education has been developed to solve the drawbacks of simulation-based education while preserving positive learning outcomes. OBJECTIVES: To compare the effects of ASA-based education and traditional education in reducing anxiety and improving self-efficacy of junior nursing students in their maternity clinical practicum. DESIGN: This study used a two-group pre-post quasi-experimental design. The comparison group was studied first followed by the experimental group. SETTINGS: Department of Nursing and affiliated medical center at a medical university in southern Taiwan. PARTICIPANTS: We enrolled 114 junior nursing students from two different class years. METHODS: A convenience sample of junior nursing students was used in this study, with 55 in the experimental group and 59 in the comparison group. The intervention included online ASA-based education videos with pamphlets and was conducted three days a week for five weeks encompassing the maternity nursing clinical practicum. We developed and applied the Clinical Situation Anxiety Scale (CS-AS) and Clinical Situation Self-Efficacy Scale (CS-SES) before and after the intervention. Qualitative feedback was assessed after the intervention. Data were collected from both the comparison and experimental groups during the fall and spring terms of both the 2019-2020 and 2020-2021 academic years. RESULTS: Compared with the comparison group, the total CS-AS and CS-SES scores significantly improved from before to after the intervention in the experimental group. The students responded to the intervention by demonstrating clinical consistency, knowing what to do and how to do it and more confidently practicing health education. CONCLUSION: Our results suggest that ASA-based education with videos and pamphlets contributed to reducing anxiety and increasing self-efficacy in nursing students during their maternity clinical practicum.

Association between Homologous Recombination Repair Defect Status and Long-Term Prognosis of Early HER2-Low Breast Cancer: A Retrospective Cohort Study.

BACKGROUND: As a newly identified subtype of HER2-negative tumors associated with a less favorable prognosis, it remains crucial to evaluate potential prognostic and predictive factors, particularly non-invasive biomarkers, for individuals with human epidermal growth factor 2 (HER2) low early-stage breast cancer (EBC). Multiple investigations have highlighted that HER2-negative patients with EBC exhibiting high homologous recombination deficiency (HRD) scores display lower rates of pathological complete response (PCR) to neoadjuvant chemotherapy (NAC). Nevertheless, no study to date has explored the correlation between HRD and the long-term prognosis in HER2-low patients with EBC. PATIENTS AND METHODS: This retrospective observational study focuses on primary EBC sourced from The Cancer Genome Atlas dataset (TCGA). It reveals the gene mutation landscape in EBC with low HER2 expression and elucidates the tumor immune landscape across different HRD states. Utilizing bioinformatics analysis and Cox proportional models, along with the Kaplan-Meier method, the study assesses the correlation between HRD status and disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Subgroup analyses were conducted to identify potential variations in the association between HRD and prognosis. RESULTS: In the patients with HER2-low breast cancer, patients with homologous recombination related genes (HRRGs) defects had an HRD score about twice that of those without related genes mutations, and were at higher risk of acquiring ARID1A, ATM, and BRCA2 mutations. We also found that most immune cell abundances were significantly higher in EBC tumors with high HRD than in EBC tumors with low HRD or HRD-medium, particularly plasma B-cell abundance, CD8 T-cell abundance, and M1 macrophages. In addition, these tumors with HRD-high also appear to have significantly higher tumor immune scores and lower interstitial scores. Then, we analyzed the relationship between different HRD status and prognosis. There was statistical significance (P = .036 and P = .046, respectively) in DSS and PFI between the HRD-low and HRD-high groups, and patients with HRD-high EBC showed relatively poor survival outcomes. A medium HRD score (hazard ratio, HR = 2.15, 95% CI: 1.04-4.41, P = .038) was a significant risk factor for PFI. Hormone receptor positivity is an important factor in obtaining medium-high HRD score and poor prognosis. CONCLUSION: Higher HRD scores were associated with poorer PFI outcomes, particularly in people with HR+/HER2-low. Varied HRD states exhibited distinctions in HRRGs and the tumor immune landscape. These insights have the potential to assist clinicians in promptly identifying high-risk groups and tailoring personalized treatments for patients with HER2-low EBC, aiming to enhance long-term outcomes.

Deep learning combining mammography and ultrasound images to predict the malignancy of BI-RADS US 4A lesions in women with dense breasts: a diagnostic study.

OBJECTIVES: The authors aimed to assess the performance of a deep learning (DL) model, based on a combination of ultrasound (US) and mammography (MG) images, for predicting malignancy in breast lesions categorized as Breast Imaging Reporting and Data System (BI-RADS) US 4A in diagnostic patients with dense breasts. METHODS: A total of 992 patients were randomly allocated into the training cohort and the test cohort at a proportion of 4:1. Another, 218 patients were enrolled to form a prospective validation cohort. The DL model was developed by incorporating both US and MG images. The predictive performance of the combined DL model for malignancy was evaluated by sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). The combined DL model was then compared to a clinical nomogram model and to the DL model trained using US image only and to that trained MG image only. RESULTS: The combined DL model showed satisfactory diagnostic performance for predicting malignancy in breast lesions, with an AUC of 0.940 (95% CI: 0.874-1.000) in the test cohort, and an AUC of 0.906 (95% CI: 0.817-0.995) in the validation cohort, which was significantly higher than the clinical nomogram model, and the DL model for US or MG alone ( P <0.05). CONCLUSIONS: The study developed an objective DL model combining both US and MG imaging features, which was proven to be more accurate for predicting malignancy in the BI-RADS US 4A breast lesions of patients with dense breasts. This model may then be used to more accurately guide clinicians' choices about whether performing biopsies in breast cancer diagnosis.

Effects of an integrated ambulatory care program on healthcare utilization and costs in older patients with multimorbidity: a propensity score-matched cohort study.

BACKGROUND: Population aging has increased the prevalence of multimorbidity, jeopardizing the sustainability and efficiency of healthcare systems. This study aimed to evaluate the effects of an integrated ambulatory care program (IACP) on healthcare utilization and costs among older patients with multimorbidity while accounting for the confounding effects of frailty. METHODS: A retrospective cohort study using propensity matching including patients aged 65 or older with two or more chronic conditions attending the outpatient clinic at our hospital between June 1 and December 31, 2019, was conducted. Exposure was defined as receipt of IACP care. Patients not undergoing the IACP comprised the unexposed group and were matched at a ratio of 1:4 to patients undergoing the IACP group according to sex, age, Charlson Comorbidity Index score, multimorbidity frailty index score, and number of outpatient visits within 6 months before the index date. Outcomes were changes in healthcare utilization and related costs between 6 months before and after receiving IACP care. Multivariate regression analyses were used for data analysis and the Generalized Estimation Equation method was used to fit the regression models. RESULTS: A total of 166 (IACP) and 664 (non-exposed) patients were analyzed. The mean participant baseline ages were 77.15 ± 7.77 (IACP) and 77.28 ± 7.90 years (unexposed). In univariate analyses, the IACP group demonstrated greater reductions than the unexposed group in the frequency of outpatient visits (-3.16 vs. -1.36, p < 0.001), number of physicians visited (-0.99 vs. -0.17, p < 0.001), diagnostic fees (-1300 New Taiwan Dollar [NTD] vs. -520 NTD, p < 0.001), drug prescription fees (-250 NTD vs. -70 NTD, p < 0.001), and examination fees (-1620 NTD vs. -700 NTD, p = 0.014). Multivariate analyses demonstrated that patients in the IACP group experienced significant reduction in the frequency of outpatient visits (95% CI: -0.357 to -0.181, p < 0.001), number of physicians visited (95% CI: -0.334 to -0.199, p < 0.001), and overall outpatient costs (95% CI: -0.082 to -0.011, p = 0.01). However, emergency department utilization, hospitalization, and costs did not differ significantly. CONCLUSIONS: Expanding IACPs may help patients with multimorbidity reduce their use of outpatient clinics at the 6-month follow-up, reduce care fragmentation, and promote sustainability of the healthcare system.

Association of FTH1-Expressing Circulating Tumor Cells With Efficacy of Neoadjuvant Chemotherapy for Patients With Breast Cancer: A Prospective Cohort Study.

BACKGROUND: The association between different phenotypes and genotypes of circulating tumor cells (CTCs) and efficacy of neoadjuvant chemotherapy (NAC) remains uncertain. This study was conducted to evaluate the relationship of FTH1 gene-associated CTCs (F-CTC) with/without epithelial-mesenchymal transition (EMT) markers, or their dynamic changes with the efficacy of NAC in patients with non-metastatic breast cancer. PATIENTS AND METHODS: This study enrolled 120 patients with non-metastatic breast cancer who planned to undergo NAC. The FTH1 gene and EMT markers in CTCs were detected before NAC (T0), after 2 cycles of chemotherapy (T1), and before surgery (T2). The associations of these different types of CTCs with rates of pathological complete response (pCR) and breast-conserving surgery (BCS) were evaluated using the binary logistic regression analysis. RESULTS: F-CTC in peripheral blood ≥1 at T0 was an independent factor for pCR rate in patients with HER2-positive (odds ratio [OR]=0.08, 95% confidence interval [CI], 0.01-0.98, P = .048). The reduction in the number of F-CTC at T2 was an independent factor for BCS rate (OR = 4.54, 95% CI, 1.14-18.08, P = .03). CONCLUSIONS: The number of F-CTC prior to NAC was related to poor response to NAC. Monitoring of F-CTC may help clinicians formulate personalized NAC regimens and implement BCS for patients with non-metastatic breast cancer.

Level pinning of anti-PT-symmetric circuits for efficient wireless power transfer.

Wireless power transfer (WPT) technology based on magnetic resonance (a basic physical phenomenon) can directly transfer energy from the source to the load without wires and other physical contacts, and has been successfully applied to implantable medical devices, electric vehicles, robotic arms and other fields. However, due to the frequency splitting of near-field coupling, the resonant WPT system has some unique limitations, such as poor transmission stability and low efficiency. Here, we propose anti-resonance with level pinning for high-performance WPT. By introducing the anti-resonance mode into the basic WPT platform, we uncover the competition between dissipative coupling and coherent coupling to achieve novel level pinning, and construct an effective anti-parity-time (anti-PT)-symmetric non-Hermitian system that is superior to previous PT-symmetric WPT schemes. On the one hand, the eigenvalue of the anti-PT-symmetric system at resonance frequency is always pure real in both strong and weak coupling regions, and can be used to overcome the transmission efficiency decrease caused by weak coupling, as brought about by, for example, a large size ratio of the transmitter to receiver, or a long transmission distance. On the other hand, due to the level pinning effect of the two kinds of coupling mechanisms, the working frequency of the system is guaranteed to be locked, so frequency tracking is not required when the position and size of the receiver change. Even if the system deviates from the matching condition, an efficient WPT can be realized, thereby demonstrating the robustness of the level pinning. The experimental results show that when the size ratio of the transmitter coil to the receiver coil is 4.29 (which is in the weak coupling region), the transfer efficiency of the anti-PT-symmetric system is nearly 4.3 (3.2) times higher than that of the PT-symmetric system when the matching conditions are satisfied (deviated). With the miniaturization and integration of devices in mind, a synthetic anti-PT-symmetric system is used to realize a robust WPT. Anti-PT-symmetric WPT technology based on the synthetic dimension not only provides a good research platform for the study of abundant non-Hermitian physics, but also provides a means of going beyond traditional near-field applications with resonance mechanisms, such as resonance imaging, wireless sensing and photonic routing.

Nonlinear topological laser on the non-Hermitian Haldane model with higher-order corner states.

The non-Hermitian skin effect (NHSE) on the non-Hermitian Haldane model with gain and loss on the honeycomb lattice with the outline of a triangle is discussed. The NHSE only occurs on the edge of the lattice, transforming the edge modes into the higher-order corner modes. The NHSE can also occur on a lattice with only loss, which can be treated as a lattice with gain and loss as well as a global loss added to it. When the saturated gain is added to the three corner sites of the dissipative lattice, a single-mode laser system is obtained. When any one site is stimulated initially, the system will reach a saturated state depending on the distribution of the corner modes, and the stable laser light is emitted by sites at the corners.

Nucleic acid aptasensor with magnetically induced self-assembly for the detection of EpCAM glycoprotein.

A "turn-on" aptasensor for label-free and cell-free EpCAM detection was constructed by employing magnetic α-Fe2O3/Fe3O4@Au nanocomposites as a matrix for signal amplification and double-stranded complex (SH-DNA/Apt probes) immobilization through Au-S binding. α-Fe2O3/Fe3O4@Au could be efficiently assembled into uniform and stable self-assembly films via magnetic-induced self-assembly technique on a magnetic glassy carbon electrode (MGCE). The effectiveness of the platform for EpCAM detection was confirmed through differential pulse voltammetry (DPV). Under optimized conditions, the platform exhibited excellent specificity for EpCAM, and a strong linear correlation was observed between the current and the logarithm of EpCAM protein concentration in the range 1 pg/mL-1000 pg/mL (R2 = 0.9964), with a limit of detection (LOD) of 0.27 pg/mL. Furthermore, the developed platform demonstrated good stability during a 14-day storage test, with fluctuations remaining below 93.33% of the initial current value. Promising results were obtained when detecting EpCAM in spiked serum samples, suggesting its potential as a point-of-care (POC) testing.

A type VII-secreted lipase toxin with reverse domain arrangement.

The type VII protein secretion system (T7SS) is found in many Gram-positive bacteria and in pathogenic mycobacteria. All T7SS substrate proteins described to date share a common helical domain architecture at the N-terminus that typically interacts with other helical partner proteins, forming a composite signal sequence for targeting to the T7SS. The C-terminal domains are functionally diverse and in Gram-positive bacteria such as Staphylococcus aureus often specify toxic anti-bacterial activity. Here we describe the first example of a class of T7 substrate, TslA, that has a reverse domain organisation. TslA is widely found across Bacillota including Staphylococcus, Enterococcus and Listeria. We show that the S. aureus TslA N-terminal domain is a phospholipase A with anti-staphylococcal activity that is neutralised by the immunity lipoprotein TilA. Two small helical partner proteins, TlaA1 and TlaA2 are essential for T7-dependent secretion of TslA and at least one of these interacts with the TslA C-terminal domain to form a helical stack. Cryo-EM analysis of purified TslA complexes indicate that they share structural similarity with canonical T7 substrates. Our findings suggest that the T7SS has the capacity to recognise a secretion signal present at either end of a substrate.

Three small partner proteins facilitate the type VII-dependent secretion of an antibacterial nuclease.

IMPORTANCE: Staphylococcus aureus is an opportunistic human pathogen associated with severe infections and antimicrobial resistance. S. aureus strains utilize a type VII secretion system to secrete toxins targeting competitor bacteria, likely facilitating colonization. EsaD is a nuclease toxin secreted by the type VII secretion system in many strains of S. aureus as well as other related bacterial species. Here, we identify three small proteins of previously unknown function as export factors, required for efficient secretion of EsaD. We show that these proteins bind to the transport domain of EsaD, forming a complex with a striking cane-like conformation.

Tell me your position: Distantly supervised biomedical entity relation extraction using entity position marker.

A significant amount of textual data has been produced in the biomedical area recently as a result of the advancement of biomedical technologies. Large-scale biomedical data can be automatically obtained with the help of distant supervision. However, the noisy data brought by distant supervision methods makes relation extraction tasks more difficult. Previous work has focused more on how to restore mislabeled relationships, but little attention has been paid to the importance of labeled entity locations for relationship extraction tasks. In this paper, we present a "four-stage" model based on BioBERT and Multi-Instance Learning by using entity position markers. Firstly, the sentence is marked with position. Secondly, BioBERT, a biomedical pre-trained language model, is used in the final sentence feature vector representation not only with the global position marker but also with the start and end marker of both the head and tail entity. Thirdly, the aggregation of sentence vectors in the bag is used as the vector feature of the bag by three aggregation methods, and the performance of different sentence feature vectors combined with different bag encoding methods is discussed. At last, relation classification is performed at the bag level. According to experimental results, the presented model significantly outperforms all baseline models and contributes to noise reduction. In addition, different bag encoding methods need to match corresponding sentence encoding representation to achieve the best performance.

Molecular phylogeography of Hipposideros pratti in China.

Hipposideros pratti has low genetic diversity and was divided into two clades, the central-western clade and the eastern clade. We did not detect a clear east-to-west dispersal route along the longitudinal direction, and we found that the eastern clade spread outward from one population to another, while the central-western clade spread gradually. The glacial-interglacial period of the Quaternary influenced the migration and dispersal of H. pratti. H. pratti did not experience a significant population increase in the past, and the average population trajectory was decreasing. Given the convenient ecosystem services provided by bats, the preservation of bat populations is particularly critical. Nonetheless, we have discovered that the majority of H. pratti's distributional sites were not discovered in this study. Based on our results, it is important to apply in situ conservation measures for effective protection as soon as possible.

Passive white light cavities with metal coatings.

White light cavities with broadband resonance are usually filled with negative dispersion medium, which inevitably leads to gain. In this article, pure passive white light cavities are designed, in which negative dispersion medium is no longer necessary. Theoretically, if the reflection phase of the cavity wall can exhibit a negative dispersion slope, then it can also satisfy white light cavities conditions without medium. In practice, the negative dispersion property of the cavity wall can be realized by two metal coatings with different reflection coefficients. Therefore, our white light cavities are composite cavities, in which the main cavity provides resonance while the auxiliary cavity forms the cavity wall, providing negative dispersion reflection phase. Further, atomic gas can be employed to improve the performance of the white light cavities. Atomic gas exploits effects such as Electromagnetic Induced Transparency (EIT), enabling the white light cavities to be controlled by coherent driving field. With the passive characters, our design can be realized and implemented much more easily.

Osthole protects H9c2 cardiomyocytes against trastuzumab-induced damage by enhancing autophagy through the p38MAPK/mTOR signaling pathway.

Trastuzumab (TRZ) is a novel targeted anti-tumor agent that significantly improve the survival of patients with human epidermal growth factor receptor (HER2) positive breast cancer. However, its clinical application is limited due to the side effects of cardiotoxicity. Osthole (OST), a coumarin derivative isolated from Cnidium monnieri (L.) Cusson, has previously demonstrated cardioprotective effects. The aim of this study was to observe the protective effect of OST on TRZ-induced cardiomyocytes damage and to explore its potential mechanism. The results showed that OST pretreatment could significantly inhibit TRZ-induced cardiomyocytes damage, markedly increase the ratio of LC3II/I and Beclin-1 protein expression, and reduce the protein expression of p62. OST pretreatment significantly attenuated oxidative stress and apoptosis induced by TRZ, as evidenced by reducing intracellular ROS level, the Bax/Bcl-2 ratio, and Caspase-3 protein expression. Additionally, OST markedly increased the phosphorylation level of p38MAPK and decreased the mTOR phosphorylation level. However, the effects of OST on enhancing autophagy, reducing oxidative stress, apoptosis, and the phosphorylation level of mTOR were reversed after the addition of 3-MA or SB203580. Molecular docking results indicated that OST exerted a good binding ability with the p38MAPK protein. Our findings suggested that OST could protect TRZ-induced cardiomyocytes damage by enhancing autophagy via the p38MAPK/mTOR signaling pathway.

The early negative bias of social semantics: evidence from behavioral and ERP studies.

BACKGROUND: Compared to nonsocial information, the human brain is more highly sensitive to social information. As a kind of typical social semantic information, the words describing person traits differ from the nonsocial semantic information describing inanimate objects in many ways. It remains to be seen whether the processing of trait words has a valence asymmetric and whether it differs from the processing of nonsocial semantic information in terms of behavioral responses and neural temporal processes. METHOD: Taking person and object names as priming stimuli and adjective words only used for describing humans or objects as target stimuli, the present study aimed to investigate the processing characteristics of social and nonsocial semantic information by recording both behavioral and ERP data. RESULTS: Behavioral results showed that the response times for negative words were significantly slower than those for positive words whether for social or nonsocial semantic information. The accuracy rates of negative words were significantly lower than those of positive words when the targets were social words which is contrary to the nonsocial words. The ERP results indicated that there was a negative bias effect on the processing of both types of information during the whole time course of brain neural activity; that is, the P2, N400, and LPP amplitudes elicited by negative words were larger than those elicited by positive words; However, the negative bias effect of social semantic information started at the early perceptual stage which was significantly earlier than the onset of negative bias of nonsocial semantic information, and was significantly affected by the prime type. In addition, there was a significant semantic conflict N400 effect only for nonsocial semantic information. CONCLUSIONS: Overall, the present study revealed the existence of an early negative bias of social information and provided evidence for the specificity of social information.