Exploring Healthcare Providers' Difficulties and Strategies when Caring for Community-Dwelling People With Dementia Who are at Risk of Getting Lost.

Caring for patients with dementia at risk of getting lost is challenging for community healthcare providers. Through semi-structured interviews with 25 participants, we examined the challenges faced by these providers and the strategies they employed. We identified the following themes of challenging parts: (a) the disturbance caused by behavioral and psychological symptoms in dementia; (b) difficulty in helping older family caregivers to keep the patient from going out; (c) difficulty in changing the attitudes of the family members; families' unawareness of the risk of getting lost. We also identified the following strategies to mitigate these themes: (a) detecting the risk of getting lost through early assessment; (b) encouraging the family to use resources or devices to prevent the patient from getting lost; (c) educating the family to manage behavior and psychological symptoms of dementia; (d) strengthening the patient's crisis awareness.

Electro-optically tunable optical delay on a lithium niobate photonic chip.

An approach for continuous tuning of on-chip optical delay with a microring resonator is proposed and demonstrated. By introducing an electro-optically tunable waveguide coupler, the bus waveguide to the resonance coupling can be effectively tuned from the under-coupling regime to the over-coupling regime. The optical delay is experimentally characterized by measuring the relative phase shift between lasers and shows a large dynamic range of delay from -600 to 600 ps and an efficient tuning of delay from -430 to -180 ps and from 40 to 240 ps by only a 5 V voltage.

2024 multidisciplinary consensus on image-guided lung tumor ablation from the Taiwan Academy of Tumor Ablation.

In this article, the multidisciplinary team of the Taiwan Academy of Tumor Ablation, who have expertise in treating lung cancer, present their perspectives on percutaneous image-guided thermal ablation (IGTA) of lung tumors. The modified Delphi technique was applied to reach a consensus on clinical practice guidelines concerning ablation procedures, including a comprehensive literature review, selection of panelists, creation of a rating form and survey, and arrangement of an in-person meeting where panelists agreed or disagreed on various points. The conclusion was a final rating and written summary of the agreement. The multidisciplinary expert team agreed on 10 recommendations for the use of IGTA in the lungs. These recommendations include terms and definitions, line of treatment planning, modality, facility rooms, patient anesthesia settings, indications, margin determination, post-ablation image surveillance, qualified centers, and complication ranges. In summary, IGTA is a safe and feasible approach for treating primary and metastatic lung tumors, with a relatively low complication rate. However, decisions regarding the ablation technique should consider each patient's specific tumor characteristics.

Discovery of Dual MER/AXL Kinase Inhibitors as Bifunctional Small Molecules for Inhibiting Tumor Growth and Enhancing Tumor Immune Microenvironment.

A series of bifunctional compounds have been discovered for their dual functionality as MER/AXL inhibitors and immune modulators. The furanopyrimidine scaffold, renowned for its suitability in kinase inhibitor discovery, offers at least three distinct pharmacophore access points. Insights from molecular modeling studies guided hit-to-lead optimization, which revealed that the 1,3-diketone side chain hybridized with furanopyrimidine scaffold that respectively combined amino-type substituent and 1H-pyrazol-4-yl substituent on the top and bottom of the aryl regions to produce 22 and 33, exhibiting potent antitumor activities in various syngeneic and xenograft models. More importantly, 33 demonstrated remarkable immune-modulating activity by upregulating the expression of total T-cells, cytotoxic CD8+ T-cells, and helper CD4+ T-cells in the spleen. These findings underscored the bifunctional capabilities of 33 (BPR5K230) with excellent oral bioavailability (F = 54.6%), inhibiting both MER and AXL while modulating the tumor microenvironment and highlighting its diverse applicability for further studies to advance its therapeutic potential.

Nontraumatic intraoperative pulmonary nodule localization with laser guide stamping in a hybrid operating room.

Lung nodule localization using conventional image-guided video-assisted thoracoscopic surgery involves lung puncture, which increases the risk of needle-related complications. We aimed to evaluate the feasibility and safety of a single-stage non-invasive laser-guided stamping localization technique followed by resection under general anesthesia in a hybrid operating room. We retrospectively reviewed consecutive patients who underwent thoracoscopic surgery for small pulmonary nodules using laser-guided dye-stamping localization methods in a hybrid operating room between June 2023 and October 2023. During the study period, 18 patients with 20 lesions underwent single-stage intraoperative image-guided stamping video-assisted thoracoscopic surgery in the hybrid operating room. The median size of the nodules was 7.4 mm (interquartile range [IQR] 5.7-9.8 mm), and median distance from the pleural surface was 9.8 mm (IQR 7.7-14.6 mm). The median localization time was 26 min (IQR 23-34 min), whereas median operation time was 69 min (IQR 62-87 min). The total median operating room time was 146 min (IQR 136-157 min). Twelve patients underwent less than two cone-beam computed tomography scans, while 6 underwent more than two scans. The total median dose area product, including cone-beam computed tomography scans, was 5731.4 uGym2. No localization-related complications were observed, and the postoperative length of stay was 1 day (IQR 1-2 days). The single-stage image-guided pleural stamping technique for localizing small pulmonary nodules in a hybrid operating room is feasible and safe. Future research with larger cohorts is required to further explore the benefits of this workflow.

CDK7/CDK9 mediates transcriptional activation to prime paraptosis in cancer cells.

BACKGROUND: Paraptosis is a programmed cell death characterized by cytoplasmic vacuolation, which has been explored as an alternative method for cancer treatment and is associated with cancer resistance. However, the mechanisms underlying the progression of paraptosis in cancer cells remain largely unknown. METHODS: Paraptosis-inducing agents, CPYPP, cyclosporin A, and curcumin, were utilized to investigate the underlying mechanism of paraptosis. Next-generation sequencing and liquid chromatography-mass spectrometry analysis revealed significant changes in gene and protein expressions. Pharmacological and genetic approaches were employed to elucidate the transcriptional events related to paraptosis. Xenograft mouse models were employed to evaluate the potential of paraptosis as an anti-cancer strategy. RESULTS: CPYPP, cyclosporin A, and curcumin induced cytoplasmic vacuolization and triggered paraptosis in cancer cells. The paraptotic program involved reactive oxygen species (ROS) provocation and the activation of proteostatic dynamics, leading to transcriptional activation associated with redox homeostasis and proteostasis. Both pharmacological and genetic approaches suggested that cyclin-dependent kinase (CDK) 7/9 drive paraptotic progression in a mutually-dependent manner with heat shock proteins (HSPs). Proteostatic stress, such as accumulated cysteine-thiols, HSPs, ubiquitin-proteasome system, endoplasmic reticulum stress, and unfolded protein response, as well as ROS provocation primarily within the nucleus, enforced CDK7/CDK9-Rpb1 (RNAPII subunit B1) activation by potentiating its interaction with HSPs and protein kinase R in a forward loop, amplifying transcriptional regulation and thereby exacerbating proteotoxicity leading to initiate paraptosis. The xenograft mouse models of MDA-MB-231 breast cancer and docetaxel-resistant OECM-1 head and neck cancer cells further confirmed the induction of paraptosis against tumor growth. CONCLUSIONS: We propose a novel regulatory paradigm in which the activation of CDK7/CDK9-Rpb1 by nuclear proteostatic stress mediates transcriptional regulation to prime cancer cell paraptosis.

Cone Beam CT Derived Laser-Guided Percutaneous Lung Ablation: Minimizing Needle-Related Complications Under General Anesthesia with Lung Separation.

RATIONALE AND OBJECTIVES: Percutaneous lung tumor ablations are mostly performed in computed tomography (CT) rooms under local anesthesia with conscious sedation. However, maintaining the breath-hold phase during this can be challenging, affecting image quality and increasing complications. With the advent of hybrid operating rooms (HORs), this procedure can be performed with endotracheal tube (ETGA) intubation under general anesthesia with lung separation, ensuring precise imaging in a single-stage setting. Lung separation provides surgical exposure of one lung while ensuring ample gas exchange with the other. This study evaluated tumor ablations performed in an HOR equipped with cone beam CT and laser guidance. MATERIALS AND METHODS: This retrospective study included patients who underwent lung tumor ablation under general anesthesia with an ETGA in an HOR between July 2020 and May 2023. Anesthesia considerations, perioperative management, and postoperative follow-ups were evaluated. RESULTS: 65 patients (78 tumors) underwent ablation using two types of lung ventilation methods including a single-lumen tube with a blocker (SLT/BL) (n = 15) and double-lumen tube (DLT) (n = 50). Most patients experienced desaturation during the apnea phase of dynamic CT and needling. The average SpO2 value was significantly lower in the DLT group than in the SLT/BL group during the procedure (81.1% versus 88.7%, P = 0.033). Five, three, and two patients developed pneumothorax, subcutaneous emphysema, and pleural effusion, respectively. CONCLUSION: Percutaneous ablation under general anesthesia with endotracheal intubation and lung separation performed in HORs was feasible and safe. The setup minimized complication risks and maintained a balance between patient safety and successful procedures.

Psychological Distress, Multicare Needs and Social Resource Utilisation of Family Caregivers of People With Dementia: A Descriptive-Correlational Study.

BACKGROUND: The population of people with dementia increases yearly, imposing a growing burden on family caregivers. Psychological distress impacts the mental health of family caregivers of people with dementia. Caregiver psychological distress can result in increased social resource utilisation and unmet multicare needs. PURPOSE: The study explored the psychological distress of family caregivers of people with dementia and examined the impact on social resource utilisation and multicare needs. METHODS: A descriptive-correlational study collected data in Taiwan from a cross-sectional sample of family caregivers of people with dementia using a self-report questionnaire. Data were analysed using linear and logistic regression. RESULTS: A total of 301 caregivers provided data for analysis. Nearly two-thirds of caregivers were female with a mean age of 57 years old (SD = 12). Over half of the family caregivers of people with dementia experienced mild-to-moderate psychological distress. The greater the psychological distress, the greater the probability of using social resources (1.09 times per 1-point increase, p = 0.002). Psychological distress was positively associated with the number of caregivers' care needs (ß = 0.371, p < 0.001). CONCLUSIONS: Findings of this study can assist healthcare professionals in better understanding the psychological distress and care needs of caregivers. Services designed to meet the needs of family caregivers will improve psychological distress.

[Corrigendum] Next­generation sequencing analysis reveals that MTH­3, a novel curcuminoid derivative, suppresses the invasion of MDA­MB­231 triple­negative breast adenocarcinoma cells.

Subsequently to the publication of the article, an interested reader drew to the authors' attention that, in Fig. 2A on p. 5, the 'Control  (24 h)' and 'MTH­3 (1 µM; 24 h)' data panels contained partially overlapping data, such that they appeared to have been derived from the same original source. The authors have examined their original data, and realized that this error arose inadvertently as a consequence of having compiled this figure incorrectly. The revised version of Fig. 2, featuring the data from one of the repeated experiments in Fig. 2A, is shown below. The revised data shown for this figure do not affect the overall conclusions reported in the paper. The authors apologize to the Editor of Oncology Reports and to the readership for any inconvenience caused. [Oncology Reports 46: 133, 2021; DOI: 10.3892/or.2021.8084].

Ni-CoSe2 heterojunction coated by N-doped carbon for modified separators of high-performance Li-sulfur batteries.

Functional separators modified by transition metal compounds have been proven to be effective in suppressing the shuttle effect of polysulfides and accelerating sluggish electrode dynamics in lithium-sulfur batteries (LSBs). However, the behaviors of heterojunctions composed of transition metals and their compounds in LSBs are still rarely studied. Herein, we report a novel Ni-CoSe2 heterostructure coated with nitrogen-doped carbon. Compared to homogeneous cobalt diselenide, it exhibits much stronger adsorption and catalytic conversion abilities towards polysulfides. With the modified separators, the lithium-sulfur batteries exhibit significantly improved capacity retention and reduced polarization during cycling.

Augmented fluoroscopy-guided dye localization for small pulmonary nodules in hybrid operating room: intrathoracic stamping versus transbronchial marking.

PURPOSE: We developed a novel augmented fluoroscopy-guided intrathoracic stamping technique for localizing small pulmonary nodules in the hybrid operating room. We conducted an observational study to investigate the feasibility of this technique and retrospectively compared two augmented fluoroscopy-guided approaches: intrathoracic and transbronchial. METHODS: From August 2020 to March 2023, consecutive patients underwent single-stage augmented fluoroscopy-guided localization under general anaesthesia. This included intrathoracic stamping and bronchoscopic lung marking, followed by thoracoscopic resection in a hybrid operating room. Comparative analyses were performed between the two groups. RESULTS: The data of 50 patients in the intrathoracic stamping and 67 patients in the bronchoscopic lung marking groups were analysed. No significant difference was noted in demographic data between the groups, except a larger lesion depth in the bronchoscopic lung marking group (14.7 ± 11.7 vs 11.0 ± 5.8 mm, p = 0.029). Dye localization was successfully performed in 49 intrathoracic stamping group patients (98.0%) and 67 bronchoscopic lung marking group patients (100%). No major procedure-related complications occurred in either group; however, the time flow (total anaesthesia time/global operating room time) was longer, and the radiation exposure (fluoroscopy duration/total dose area product) was larger in the bronchoscopic lung marking group. CONCLUSIONS: Augmented fluoroscopic stamping localization under intubated general anaesthesia is feasible and safe, providing an alternative with less global operating room time and lower radiation exposure for image-guided thoracoscopic surgery in the hybrid operating room.

Inhomogeneous Au2S for Photoacoustic Imaging and Photodynamic Tumor Therapy Based on Different Forms of Energy Dissipation.

Nanomaterials with unique structures and components play a crucial role in nanomedicine. In this study, we discovered that the inhomogeneous Au2S constructed by cation exchange and acid etching could dissipate energy in different forms after absorbing multichromatic light, which could be used to achieve the integrated diagnosis and treatment of tumors, respectively. Folic acid modified Au2S ringed nanoparticles (FA-Au2S RNs) with an assembly-like structure were demonstrated to result in better PA imaging performance and generate more reactive oxygen species (O2·-, ·OH, and 1O2) than folic acid modified Au2S triangular nanoparticles (FA-Au2S TNs). Finite element analyses determined the reason for the high absorbance properties and synergistic enhancement of plasma resonance in the assembly-like structure of Au2S RNs. Both FA-Au2S nanostructures were modified with folic acid and injected into 4T1 tumor-bearing mice via the tail vein. The best PA imaging contrast was obtained under 700 nm laser illumination, and the most effective PDT antitumor activity was achieved under 1064 nm laser illumination. The PA average of the tumor in the FA-Au2S RN group was approximately 2 times higher than that of the FA-Au2S TN group at 24 h of injection. The PA imaging results of intratumorally injected FA-Au2S RNs proved that they were still able to show better PA signal enhancement at 24 h postinjection. Our study demonstrates that FA-Au2S nanomaterials with unique structures and special properties can be reliably produced using strictly controlled chemical synthesis. It further provides a strategy for the construction of highly sensitive PA imaging platforms and efficient PDT antitumor agents that exploit wavelength-dependent energy dissipation mechanisms.

A faster killing effect of plastid-mediated RNA interference on a leaf beetle through induced dysbiosis of the gut bacteria.

The expression of double-stranded RNAs (dsRNAs) from the plastid genome has been proven to be an effective method for controlling herbivorous pests by targeting essential insect genes. However, there are limitations to the efficiency of plastid-mediated RNA interference (PM-RNAi) due to the initial damage caused by the insects and their slow response to RNA interference. In this study, we developed transplastomic poplar plants that express dsRNAs targeting the ß-Actin (dsACT) and Srp54k (dsSRP54K) genes of Plagiodera versicolora. Feeding experiments showed that transplastomic poplar plants can cause significantly higher mortality in P. versicolora larvae compared with nuclear transgenic or wild-type poplar plants. The efficient killing effect of PM-RNAi on P. versicolora larvae was found to be dependent on the presence of gut bacteria. Importantly, foliar application of a gut bacterial strain, Pseudomonas putida, will induce dysbiosis in the gut bacteria of P. versicolora larvae, leading to a significant acceleration in the speed of killing by PM-RNAi. Overall, our findings suggest that interfering with gut bacteria could be a promising strategy to enhance the effectiveness of PM-RNAi for insect pest control, offering a novel and effective approach for crop protection based on RNAi technology.

Photonic time-delayed reservoir computing based on series-coupled microring resonators with high memory capacity.

On-chip microring resonators (MRRs) have been proposed to construct time-delayed reservoir computing (RC) systems, which offer promising configurations available for computation with high scalability, high-density computing, and easy fabrication. A single MRR, however, is inadequate to provide enough memory for the computation task with diverse memory requirements. Large memory requirements are satisfied by the RC system based on the MRR with optical feedback, but at the expense of its ultralong feedback waveguide. In this paper, a time-delayed RC is proposed by utilizing a silicon-based nonlinear MRR in conjunction with an array of linear MRRs. These linear MRRs possess a high quality factor, providing enough memory capacity for the RC system. We quantitatively analyze and assess the proposed RC structure's performance on three classical tasks with diverse memory requirements, i.e., the Narma 10, Mackey-Glass, and Santa Fe chaotic timeseries prediction tasks. The proposed system exhibits comparable performance to the system based on the MRR with optical feedback, when it comes to handling the Narma 10 task, which requires a significant memory capacity. Nevertheless, the dimension of the former is at least 350 times smaller than the latter. The proposed system lays a good foundation for the scalability and seamless integration of photonic RC.

Low power consumption grating magneto-optical trap based on planar elements.

The grating-based magneto-optical trap (GMOT) is a promising approach for miniaturizing cold-atom systems. However, the power consumption of a GMOT system dominates its feasibility in practical applications. In this study, we demonstrated a GMOT system based on planar elements that can operate with low power consumption. A high-diffraction-efficiency grating chip was used to cool atoms with a single incident beam. A planar coil chip was designed and fabricated with a low power consumption nested architecture. The grating and coil chips were adapted to a passive pump vacuum chamber, and up to 106 87Rb atoms were trapped. These elements effectively reduce the power consumption of the GMOT and have great potential for applications in practical cold-atom-based devices.

Cytokinin oxidase gene CKX5 is modulated in the immunity of Arabidopsis to Botrytis cinerea.

In our previous work, cytokinin (CK) signaling and biosynthesis were found to be modulated during Arabidopsis defense against infection by the necrotrophic pathogen Botrytis cinerea. Notably, the expression level of CYTOKININ OXIDASE/DEHYDROGENASE 5 (CKX5) was significantly induced in B. cinerea-infected leaves and later in distant B. cinerea-untreated leaves of the same plant. To confirm and determine how CKX5 is involved in the response to B. cinerea infection, transcript levels of CKX family genes were analyzed in B. cinerea-inoculated leaves, and only CKX5 was remarkably induced by B. cinerea infection. Furthermore, CKX5-overexpressing Arabidopsis plants were more resistant to B. cinerea than wild-type plants. Transcription factors (TFs) binding to the CKX5 promoter were then screened by yeast one-hybrid assays. Quantitative Real-Time Reverse Transcription PCR (qRT-PCR) analysis further showed that genes encoding TFs, including WRKY40, WRKY33, ERF6, AHL15, AHL17, ANAC003, TCP13 and ANAC019, were also strongly induced in infected leaves, similar to CKX5. Analysis of ERF6-overexpressing plants and ERF6-and AHL15-knockout mutants indicated that ERF6 and AHL15 are involved in plant immunity to B. cinerea. Furthermore, CKX5 upregulation by B. cinerea infection was affected when ERF6 or AHL15 levels were altered. Our work suggests that CKX5 levels are controlled by the plant defense system to defend against attack by the pathogen B. cinerea.

Numerical analysis of on-chip acousto-optic modulators for visible wavelengths.

On-chip acousto-optic modulators that operate at an optical wavelength of 780 nm and a microwave frequency of 6.835 GHz are proposed. The modulators are based on a lithium-niobate-on-sapphire platform and efficiently excite surface acoustic waves and exhibit strong interactions with tightly confined optical modes in waveguides. In particular, a high-efficiency phase modulator and single-sideband mode converter are designed. We found that for both microwave and optical wavelengths below 1 µm, the interactions at the cross-sections of photonic waveguides are sensitive to the waveguide width and are significantly different from those in previous studies. Our designed devices have small footprints and high efficiencies, making them suitable for controlling rubidium atoms and realizing hybrid photonic-atomic chips. Furthermore, our devices have the potential to extend the acousto-optic modulators to other visible wavelengths for other atom transitions and for visible light applications, including imaging and sensing.

B cell receptor repertoire analysis in primary Sjogren's syndrome salivary glands identifies repertoire features associated with clinical activity.

BACKGROUND: Primary Sjogren's syndrome (pSS) is a complex autoimmune disease featuring damage to salivary and lacrimal glands, with the possibility of manifestations across multiple organs. Antibody-producing B cells have long been appreciated to play a significant role in pSS pathogenesis, with a number of autoreactive antibody species having been identified to be elevated in pSS patients. While several studies have attempted to characterize the BCR repertoires of peripheral blood B cells in pSS patients, much remains unknown about the repertoire characteristics of gland-infiltrating B cells. METHODS: Through paired scRNAseq and scBCRseq, we profiled the BCR repertoires of both infiltrating and circulating B cells in a small cohort of patients. We further utilize receptor reconstruction analyses to further investigate repertoire characteristics in a wider cohort of pSS patients previously profiled through RNAseq. RESULTS: Via integrated BCR and transcriptome analysis of B cell clones, we generate a trajectory progression pattern for infiltrated memory B cells in pSS. We observe significant differences in BCR repertoires between the peripheral blood and labial gland B cells of pSS patients in terms of relative expansion, isotype usage, and BCR clustering. We further observe significant decreases in IgA2 isotype usage among pSS patient labial and parotid gland B cells these analyses relative to controls as well as a positive correlation between kappa/lambda light chain usage and clinical disease activity. CONCLUSIONS: Through BCR repertoire analysis of pSS patient salivary glands, we identify a number of novel repertoire characteristics that may serve as useful indicators of clinical disease and disease activity. By collecting these BCR repertoires into an accessible database, we hope to also enable comparative analysis of patient repertoires in pSS and potentially other autoimmune disorders.

Bioactive solanidane steroidal alkaloids from Solanum lyratum.

Six previously unreported solanidane steroidal alkaloids, namely lyrasolanosides A-F, were isolated from Solanum lyratum. In addition, five known steroidal alkaloids were also identified. The structures of these compounds were determined through the use of NMR, HRESIMS,UV, IR and ECD analysis. To assess their bioactivities, the cytotoxic effects of the six previously unreported compounds were evaluated on A549 cells. The results revealed that lyrasolanoside B (2) exhibited the highest potency among them. Lyrasolanoside B (2) exhibited significant inhibition of cell migration, invasion, and adhesion dramatically. Mechanistically, it was found to suppress the activity of JAK2/STAT3 signaling pathway by downregulating the expression of phosphorylated JAK2/STAT3 in an exosome-dependent manner. In addition, lyrasolanoside B (2) was found to significantly upregulate the expression of E-cadherin and downregulate the expression of N-cadherin and vimentin. These findings indicate that lyrasolanoside B (2) inhibits the metastasis of A549 cells by suppressing exosome-mediated EMT. These findings suggest that lyrasolanoside B (2) may inhibit the metastasis of lung cancer by regulating A549-derived exosomes.