ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition.

High-risk neuroblastoma (NB) is a significant clinical challenge. MYCN and Anaplastic Lymphoma Kinase (ALK), which are often involved in high-risk NB, lead to increased replication stress in cancer cells, suggesting therapeutic strategies. We previously identified an ATR (ataxia telangiectasia and Rad3-related)/ALK inhibitor (ATRi/ALKi) combination as such a strategy in two independent genetically modified mouse NB models. Here, we identify an underlying molecular mechanism, in which ALK signaling leads to phosphorylation of ATR and CHK1, supporting an effective DNA damage response. The importance of ALK inhibition is supported by mouse data, in which ATRi monotreatment resulted in a robust initial response, but subsequent relapse, in contrast to a 14-d ALKi/ATRi combination treatment that resulted in a robust and sustained response. Finally, we show that the remarkable response to the 14-d combined ATR/ALK inhibition protocol reflects a robust differentiation response, reprogramming tumor cells to a neuronal/Schwann cell lineage identity. Our results identify an ability of ATR inhibition to promote NB differentiation and underscore the importance of further exploring combined ALK/ATR inhibition in NB, particularly in high-risk patient groups with oncogene-induced replication stress.

Electrochemical coupling in subnanometer pores/channels for rechargeable batteries.

Subnanometer pores/channels (SNPCs) play crucial roles in regulating electrochemical redox reactions for rechargeable batteries. The delicately designed and tailored porous structure of SNPCs not only provides ample space for ion storage but also facilitates efficient ion diffusion within the electrodes in batteries, which can greatly improve the electrochemical performance. However, due to current technological limitations, it is challenging to synthesize and control the quality, storage, and transport of nanopores at the subnanometer scale, as well as to understand the relationship between SNPCs and performances. In this review, we systematically classify and summarize materials with SNPCs from a structural perspective, dividing them into one-dimensional (1D) SNPCs, two-dimensional (2D) SNPCs, and three-dimensional (3D) SNPCs. We also unveil the unique physicochemical properties of SNPCs and analyse electrochemical couplings in SNPCs for rechargeable batteries, including cathodes, anodes, electrolytes, and functional materials. Finally, we discuss the challenges that SNPCs may face in electrochemical reactions in batteries and propose future research directions.

Ultralow Auger-Assisted Interlayer Exciton Annihilation in WS2/WSe2 Moiré Heterobilayers.

Transition metal dichalcogenide (TMD) heterobilayers have emerged as a promising platform for exploring solid-state quantum simulators and many-body quantum phenomena. Their type II band alignment, combined with the moiré superlattice, inevitably leads to nontrivial exciton interactions and dynamics. Here, we unveil the distinct Auger annihilation processes for delocalized interlayer excitons in WS2/WSe2 moiré heterobilayers. By fitting the characteristic efficiency droop and bimolecular recombination rate, we quantitatively determine an ultralow Auger coefficient of 1.3 × 10-5 cm2 s-1, which is >100-fold smaller than that of excitons in TMD monolayers. In addition, we reveal selective exciton upconversion into the WSe2 layer, which highlights the significance of intralayer electron Coulomb interactions in dictating the microscopic scattering pathways. The distinct Auger processes arising from spatial electron-hole separation have important implications for TMD heterobilayers while endowing interlayer excitons and their strongly correlated states with unique layer degrees of freedom.

Increased Apolipoprotein A1 Expression Correlates with Tumor-Associated Neutrophils and T Lymphocytes in Upper Tract Urothelial Carcinoma.

An increased neutrophil-to-lymphocyte ratio (NLR) is a poor prognostic biomarker in various types of cancer, because it reflects the inhibition of lymphocytes in the circulation and tumors. In urologic cancers, upper tract urothelial carcinoma (UTUC) is known for its aggressive features and lack of T cell infiltration; however, the association between neutrophils and suppressed T lymphocytes in UTUC is largely unknown. In this study, we examined the relationship between UTUC-derived factors and tumor-associated neutrophils or T lymphocytes. The culture supernatant from UTUC tumor tissue modulated neutrophils to inhibit T cell proliferation. Among the dominant factors secreted by UTUC tumor tissue, apolipoprotein A1 (Apo-A1) exhibited a positive correlation with NLR. Moreover, tumor-infiltrating neutrophils were inversely correlated with tumor-infiltrating T cells. Elevated Apo-A1 levels in UTUC were also inversely associated with the population of tumor-infiltrating T cells. Our findings indicate that elevated Apo-A1 expression in UTUC correlates with tumor-associated neutrophils and T cells. This suggests a potential immunomodulatory effect on neutrophils and T cells within the tumor microenvironment, which may represent therapeutic targets for UTUC treatment.

Green Polymer Electrolytes Prepared by a Cost-Effective Approach.

The preparation of solid polymer electrolytes (SPEs) using poly(ethylene oxide) (PEO) typically involves incorporating fillers or undergoing chemical modifications to reduce crystallinity and enhance conductivity. PEO with a lower molecular weight, known as polyethylene glycol (PEG), exhibits higher conductivity, despite weaker mechanical strength. It is commonly employed as a plasticizer to improve the conductivity of SPEs or to fabricate PEG-based gel polymer electrolytes (GPEs). In this study, we use a straightforward approach to create innovative SPEs by blending liquid polymer electrolytes (LPEs), particularly low-molecular-weight polyethylene glycol (PEG), with a molecular weight of 400 g/mol, and sustainable poly(l-lactide) (PLLA). Solid PEG/PLLA forms are achieved by introducing 30 wt % of PLLA. Subsequently, the addition of lithium salts results in the development of novel PEG/PLLA SPEs. Another focal point of this study involves incorporating 1,3:2,4-dibenzylidene sorbitol (DBS) into these PEG/PLLA systems. DBS, an organic gelator derived from natural sugars, demonstrates self-assembly, leading to the formation of a nanofibrillar network structure. Leveraging DBS's ability to form organogels in liquid organic environments, we facilitate the transformation of low PLLA content LPEs into innovative solvent-free GPEs. Our prepared PEG/PLLA SPEs exhibited a maximum conductivity value of 4.39 × 10-5 S/cm, approximately five times higher than that of neat PEG (10000 g/mol) SPEs. The ionic conductivity exhibited a declining trend as the content of PLLA and DBS increased. However, there was an improvement in electrochemical stability. Furthermore, the incorporation of PLLA and DBS into electrolytes contributed to enhanced mechanical support and stability within the electrolyte layer. This, in turn, mitigated capacity decay and improved the cycling performance of assembled lithium-ion cells.

Supramolecular salicylic acid combined with niacinamide in chloasma: A randomized controlled trial.

BACKGROUND: No trial of supramolecular salicylic acid (SSA) for chloasma is available yet. OBJECTIVE: The purpose of this study was to assess the efficacy and safety of Bole DA 30% supramolecular salicylic acid (SSA) combined with 10% niacinamide in treating chloasma. METHODS: This multicenter (n=15), randomized, double-blind, parallel placebo-controlled trial randomized the subjects (1:1) to Bole DA 30% SSA or placebo. The primary endpoint was the effective rate after 16 weeks using the modified melasma area severity index (mMASI) [(pretreatment-posttreatment)/pretreatment×100%]. RESULTS: This study randomized 300 subjects (150/group in the full analysis set, 144 and 147 in the per-protocol set). The total mMASI score, overall Griffiths 10 score, left Griffiths 10 score, and right Griffiths 10 score were significantly lower in the Bole DA 30% SSA group than in the placebo group (all P<0.001). One study drug-related AE and one study drug-unrelated adverse events (AE) were reported in the Bole DA 30% SSA group. No AE was reported in the placebo group. CONCLUSION: Bole DA 30% SSA combined with 10% niacinamide is effective and safe for treating chloasma. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200065346.

Characteristics of the White Matter Structural Network in Individuals with Subjective Cognitive Decline with and without APOEε4 Based on Graph Theory Study.

PURPOSE: To determine whether individuals with subjective cognitive decline (SCD) have changes in whole-brain network characteristics and intracerebral node characteristics in the structural network, and whether there is a difference between SCD with and without Apolipoprotein E4 (APOEε4). METHODS: This cross-sectional study included 36 individuals without SCD without APOEε4 (healthy control, HC group), 21 individuals with SCD with APOEε4 (APOEε4+ group), and 33 individuals with SCD without APOEε4 (APOEε4- group). The white matter structural network was constructed using the fractional anisotropy (FA) based deterministic fiber tracking method. Graph theory was used to analyze the whole-brain network characteristics and intracerebral node characteristics of the three groups. RESULTS: Regarding the whole-brain network characteristics, all three groups exhibited small-worldness in their structural networks. The clustering coefficient (Cp) and local efficiency (Eloc) in the APOEε4+ and APOEε4- groups were significantly lower than in the HC group (p < 0.05), but no significant difference in Cp or Eloc was observed between the APOEε4+ and APOEε4- groups. Regarding intracerebral node characteristics, there were significant differences in some brain regions, mainly the default mode network (DMN), the occipital lobe, the temporal lobe, and subcortical regions. The change in intracerebral node characteristics was different between the APOEε4+ group and the APOEε4- group. CONCLUSIONS: Individuals with SCD demonstrate changes in whole-brain network characteristics and intracerebral node characteristics in the structural network. Moreover, differences exist between APOEε4+ and APOEε4- individuals.

Acceptability and tolerability of alcohol-based hand rubs among health workers and concessionaires in Malaysia during the COVID pandemic: a hospital-wide cross-sectional study using a modified WHO protocol.

This study evaluated the acceptability and tolerability of three alcohol-based hand rubs (ABHRs) at Sarawak General Hospital, Malaysia. Conducted from 12-26 November 2021 using a modified WHO Protocol, it involved a survey among health workers and concessionaires, with a 35% response rate (1,598 of 4,628 participants). The majority were nurses (60.8%), with the medical division most represented (28.4%). Most respondents (93.2%) used ABHRs at least five days a week and found them easily accessible (72.3%). Product B was the preferred ABHR (65%), primarily for its color and fragrance, surpassing WHO's 50% approval rate in these aspects. However, no other product features met WHO criteria. There were no significant differences in self-reported skin tolerability across the products, and none achieved overall WHO approval. These results offer important insights for ABHR selection in developing countries and highlight the value of the WHO Protocol in assessing product acceptability and tolerability.

Next-Generation Sequencing in Lung Cancers-A Single-Center Experience in Taiwan.

Background and Objectives: Lung cancer is a leading cause of cancer mortality in Taiwan. With rapid advancement of targeted therapeutics in non-small cell lung cancers, next-generation sequencing (NGS) is becoming an important tool for biomarker testing. In this study, we describe institutional experience of NGS analysis in non-small cell carcinoma (NSCLC). Materials and Methods: A cohort of 73 cases was identified from the institutional pathology archive in the period between November 2020 and December 2022. Results: Adenocarcinoma was the most common histologic type (91.8%). Most patients presented with stage IIIB and beyond (87.7%). Twenty-nine patients (39.7%) were evaluated at the time of initial diagnosis, while the others had received prior chemotherapy or targeted therapy. The most frequently mutated gene was EGFR (63%), and this was followed by TP53 (50.7%), KRAS (13.7%), RB1 (13.7%), and CDKN2A (13.7%). Clinically actionable mutations associated with a guideline-suggested targeted therapy were identified in 55 cases (75.3%) overall, and in 47.1% of cases excluding EGFR TKI-sensitizing mutation. Biomarkers other than EGFR TKI-sensitizing mutations were compared. Cases without TKI-sensitizing EGFR mutation had more level 1 or 2 biomarkers (excluding EGFR TKI-sensitizing mutations) than cases with TKI-sensitizing EGFR mutations (47.1% versus 20.1%, p = 0.016). Progressive disease was associated with co-occurrence of clinically actionable mutations (20.5% versus 0%, p < 0.05). Eight of the nine cases with co-occurring actionable genetic alternations had an EGFR mutation. After an NGS test, 46.1% of actionable or potentially actionable genetic alternations led to patients receiving a matched therapy. Conclusions: Our study demonstrated that NGS analysis identifies therapeutic targets and may guide treatment strategies in NSCLC. NGS tests may be advantageous over multiple single-gene tests for optimization of treatment plans, especially for those with non-EGFR mutations or those with progressive disease.

Evaluating the Risk of Malignancies of the Diagnostic Categories Proposed by the World Health Organization System for Reporting Lung Cytopathology: A 2-Year Single Institutional Experience.

INTRODUCTION: The WHO System of Reporting Lung Cytopathology proposed a 5-tiered system in 2023. We report the risk of malignancies (ROMs) of bronchial washing/lavage and percutaneous fine-needle aspiration (FNA) specimens. We also evaluated the change of ROMs when image correlation is required. METHODS: Lung cytology cases in 2021 and 2022 with histologic follow-up were included. CT reports were reviewed to identify cases with a solid nodule/tumor but benign cytological findings. These were reassigned from the "benign" to "non-diagnostic" category, and the ROMs were re-estimated. RESULTS: A total of 1,031 bronchial washing/lavage and 206 FNAs were identified. The ROMs of bronchial washing/lavage were "non-diagnostic" 56.5% (13/23), "benign" 41.9% (320/764), "atypical" 71.7% (71/99), "suspicious for malignancy" 94.7% (72/76), and "malignant" 100% (70/70). The ROMs of FNAs were "non-diagnostic" 66% (33/50), "benign" 58.2% (39/67), "atypical" 70% (28/40), "suspicious for malignancy" 96.2% (25/26), and "malignant" 100% (70/70). When image finding was considered, cases initially assigned as "benign" were re-classified to "non-diagnostic" with decreases in ROMs for the "benign" category. CONCLUSIONS: Malignancy risks associated with the WHO System of Reporting Lung Cytopathology diagnostic groups were reported. Image correlation for the "benign" category led to a decrease in case number and ROM.

Buried Interface Passivation Using Organic Ammonium Salts for Efficient Inverted CsMAFA Perovskite Solar Cell Performance.

This study uses different doping ratios of CsCl and MACl dual additives to improve the quality of the perovskite, where CsCl reduces the perovskite trap density and increases the resistance of charge recombination, and MACl was used to improve the phase stability. Finally, the composition of Cs0.1MA0.09FA0.81PbCl0.14I2.86 perovskite solar cell (PeSC) can achieve better open-circuit voltage (Voc), short-circuit current density (Jsc), and photoelectric conversion efficiency (PCE). To achieve a better PCE of PeSC, the use of organic ammonium salt butane-1,4-diammonium iodide (BDAI2) to passivate the perovskite bottom surface (buried interface) can effectively suppress the formation of defects at the perovskite buried interface, obtain higher crystallinity, and thereby reduce the probability of carrier recombination. The Jsc, fill factor (FF), and PCE of the PeSC based on BDAI2 passivation increased from 24.0 mA cm-2, 74.1%, and 18.6% to 24.5 mA cm-2, 79.9%, and 20.5%, respectively.

Pretrained Quantum-Inspired Deep Neural Network for Natural Language Processing.

Natural language processing (NLP) may face the inexplicable "black-box" problem of parameters and unreasonable modeling for lack of embedding of some characteristics of natural language, while the quantum-inspired models based on quantum theory may provide a potential solution. However, the essential prior knowledge and pretrained text features are often ignored at the early stage of the development of quantum-inspired models. To attacking the above challenges, a pretrained quantum-inspired deep neural network is proposed in this work, which is constructed based on quantum theory for carrying out strong performance and great interpretability in related NLP fields. Concretely, a quantum-inspired pretrained feature embedding (QPFE) method is first developed to model superposition states for words to embed more textual features. Then, a QPFE-ERNIE model is designed by merging the semantic features learned from the prevalent pretrained model ERNIE, which is verified with two NLP downstream tasks: 1) sentiment classification and 2) word sense disambiguation (WSD). In addition, schematic quantum circuit diagrams are provided, which has potential impetus for the future realization of quantum NLP with quantum device. Finally, the experiment results demonstrate QPFE-ERNIE is significantly better for sentiment classification than gated recurrent unit (GRU), BiLSTM, and TextCNN on five datasets in all metrics and achieves better results than ERNIE in accuracy, F1-score, and precision on two datasets (CR and SST), and it also has advantage for WSD over the classical models, including BERT (improves F1-score by 5.2 on average) and ERNIE (improves F1-score by 4.2 on average) and improves the F1-score by 8.7 on average compared with a previous quantum-inspired model QWSD. QPFE-ERNIE provides a novel pretrained quantum-inspired model for solving NLP problems, and it lays a foundation for exploring more quantum-inspired models in the future.

The Lived Experiences of Palliative Care Professionals in Cultivating Mindfulness: A Phenomenological Study.

Purpose: The aim of this study was to explore the essence of the lived experiences of palliative care professionals in cultivating mindfulness, with a focus on the meaning of mindfulness in their lives and how mindfulness is experienced throughout their process of caring for others. Design: This was a qualitative study using a phenomenological approach. Methods: Eleven palliative care professionals (three physicians, four nurses, three psychologists, and one spiritual care provider) partook in in-depth interviews. Data were collected from the in-depth interviews and analyzed according to the method of Giorgi. Findings: Two major themes emerged from this study. First, the palliative care professionals realized the need for self-care amid emotional burden, including recognizing their feelings of guilt and self-doubt, emotional contagion of grief, reflections of others' fragility on themself, and their self-imposed limitations. Second, they noticed the transformative impact of mindfulness on them, including detecting reconnection with their body, changes in their personal values, self-acceptance, and liberation. Conclusion: Palliative care professionals can cultivate self-acceptance and facilitate entirely new life experiences through the practice of mindfulness. For them, mindfulness is not merely a self-regulation technique but an existential epiphany, offering hope for self-care and empowerment.

The Delivery Model of Perceived Medical Service Quality Based on Donabedian's Framework.

ABSTRACT: The implementation of the National Health Insurance has transformed the medical care landscape in Taiwan, rendering perceived medical service quality (PMSQ) and patient satisfaction significant focal points in medical care management. Past studies mostly focused on the technical aspects of medical care services, while overlooking the patients' perception of services and the delivery process of PMSQ in the medical care experience. This study integrated the theoretical framework of the Donabedian SPO model and the SERVQUAL questionnaire. The survey was conducted among the outpatients of three types of medical institutions in northern Taiwan: academic medical centers, metropolitan hospitals, and local community hospitals. A total of 400 questionnaires were collected, and 315 valid questionnaires remained after eliminating the incomplete ones. This study established a PMSQ delivery model to explore patients' perceptions of medical service quality. It was found that the variable, Assurance, could deliver the PMSQ and enhance the Medical outcome (MO), while improving the variable, Tangible, in medical institutions could not significantly enhance the MO. These findings emphasize the importance of healthcare institutions prioritizing the professional background, demeanor of their healthcare staff, treatment methods, and processes over tangible elements.

"Maintain Professionalism": Nurses' Experiences in Caring for Patients with Malignant Fungating Wounds in Taiwan.

CONTEXT: Malignant fungating wounds (MFWs) occur among 5%-15% of patients with terminal cancers, the uncontrollable symptoms result in serious psychosocial issues, thereby reducing the quality of life. Caring for MFWs impacts caregivers, including healthcare personnel. While existing studies are patient-focused, the impact of care experiences and associated support for nurses has not been examined. OBJECTIVES: To explore the experiences in caring for patients with MFWs among nurses in Taiwan. METHODS: Qualitative study with a phenomenological approach by thematic analysis was conducted with semi-structured interviews. About 15 nurses who cared for patients with MFWs at local district hospitals in Southern Taiwan. RESULTS: Four themes were identified to describe the phenomenon: (1) Fear of Unpredictability (2) Maintaining Professionalism (3) Feeling Helpless (4) Rationalizing the Negatives. The themes illustrated the distress of managing physical symptoms and highlighted how nurses strived to promote comfort for patients. Nurses felt helpless about the incurable nature of MFWs but found a way to suppress their feelings. CONCLUSION: The findings suggested the need for addressing the emotional well-being of nurses who take care of patients with MFWs. Future studies should identify effective coping strategies for nurses' health when caring for this population.

Evolution of Phenotypic Variance Provides Insights into the Genetic Basis of Adaptation.

Most traits are polygenic, and the contributing loci can be identified by genome-wide association studies. The genetic basis of adaptation (adaptive architecture) is, however, difficult to characterize. Here, we propose to study the adaptive architecture of traits by monitoring the evolution of their phenotypic variance during adaptation to a new environment in well-defined laboratory conditions. Extensive computer simulations show that the evolution of phenotypic variance in a replicated experimental evolution setting can distinguish between oligogenic and polygenic adaptive architectures. We compared gene expression variance in male Drosophila simulans before and after 100 generations of adaptation to a novel hot environment. The variance change in gene expression was indistinguishable for genes with and without a significant change in mean expression after 100 generations of evolution. We suggest that the majority of adaptive gene expression evolution can be explained by a polygenic architecture. We propose that tracking the evolution of phenotypic variance across generations can provide an approach to characterize the adaptive architecture.

Elevated RACGAP1 Expression Enhances Malignant Potential in Lung Adenocarcinoma and Serves as a Prognostic Factor.

Background: While RACGAP1 is identified as a potential oncogene, its specific role in lung adenocarcinoma (LUAD) remains unclear. Methods: First, we conducted a comprehensive analysis of the role of RACGAP1 across 33 types of cancer. Subsequently, we investigated the expression levels of RACGAP1 and its impact on prognosis using data from The Cancer Genome Atlas (TCGA) database. We utilized single-cell sequencing data to explore the tumor-related processes of RACGAP1 in LUAD and validated our findings through experimental verification. Employing a consensus clustering (CC) approach, we subdivided LUAD patients into two subtypes based on RACGAP1 cell cycle-related genes (RrCCGs). These subtypes exhibited significant differences in tumor characteristics, lymph node metastasis, and recurrence. Furthermore, we evaluated the prognostic influence of RrCCGs using univariate Cox regression and least absolute shrinkage and selection operator regression models (LASSO), successfully establishing a prognostic model. Results: RACGAP1 is frequently overexpressed in various tumors and can impact the prognosis of patients with LUAD. Additionally, experimental evidence has demonstrated that low expression of RACGAP1 favors tumor cell apoptosis and restoration of the cell cycle, while high expression promotes invasion and metastasis. Through CC analysis of RrCCGs, patients were classified into two groups, with survival analysis revealing distinct prognoses and stages between the two groups. Furthermore, Cox and LASSO regression successfully constructed a prognostic model with robust predictive capability.

Gate-to-grave assessment of plastic from recycling to manufacturing of TENG: a comparison between India and Singapore.

This study assesses the viability of recycled plastic-based triboelectric nanogenerators (TENGs) for sustainable energy harvesting in India and Singapore, concurrently examining plastic waste management. Using material flow analysis and life cycle assessment, the findings revealed that in Singapore, waste-to-energy incineration has a lower environmental impact than landfilling and mechanical recycling, attributed to natural gas usage. In India, recycling offsets impacts from incineration and landfilling, contributing to a lower net environmental impact. Economic performance of a TENG module from PET recyclates showed a 20% carbon footprint reduction when scaling up from lab to industrial "freeze-drying" processes. Key challenges in TENG manufacturing processes are also assessed for future development. This research highlights the potential of recycled plastic-based TENGs in sustainable energy and waste management.

Reproductive isolation arises during laboratory adaptation to a novel hot environment.

BACKGROUND: Reproductive isolation can result from adaptive processes (e.g., ecological speciation and mutation-order speciation) or stochastic processes such as "system drift" model. Ecological speciation predicts barriers to gene flow between populations from different environments, but not among replicate populations from the same environment. In contrast, reproductive isolation among populations independently adapted to the same/similar environment can arise from both mutation-order speciation or system drift. RESULTS: In experimentally evolved populations adapting to a hot environment for over 100 generations, we find evidence for pre- and postmating reproductive isolation. On one hand, an altered lipid metabolism and cuticular hydrocarbon composition pointed to possible premating barriers between the ancestral and replicate evolved populations. On the other hand, the pronounced gene expression differences in male reproductive genes may underlie the postmating isolation among replicate evolved populations adapting to the same environment with the same standing genetic variation. CONCLUSION: Our study confirms that replicated evolution experiments provide valuable insights into the mechanisms of speciation. The rapid emergence of the premating reproductive isolation during temperature adaptation showcases incipient ecological speciation. The potential evidence of postmating reproductive isolation among replicates gave rise to two hypotheses: (1) mutation-order speciation through a common selection on early fecundity leading to an inherent inter-locus sexual conflict; (2) system drift with genetic drift along the neutral ridges.