Deep learning-based multi-frequency denoising for myocardial perfusion SPECT.

BACKGROUND: Deep learning (DL)-based denoising has been proven to improve image quality and quantitation accuracy of low dose (LD) SPECT. However, conventional DL-based methods used SPECT images with mixed frequency components. This work aims to develop an integrated multi-frequency denoising network to further enhance LD myocardial perfusion (MP) SPECT denoising. METHODS: Fifty anonymized patients who underwent routine 99mTc-sestamibi stress SPECT/CT scans were retrospectively recruited. Three LD datasets were obtained by reducing the 10 s acquisition time of full dose (FD) SPECT to be 5, 2 and 1 s per projection based on the list mode data for a total of 60 projections. FD and LD projections were Fourier transformed to magnitude and phase images, which were then separated into two or three frequency bands. Each frequency band was then inversed Fourier transformed back to the image domain. We proposed a 3D integrated attention-guided multi-frequency conditional generative adversarial network (AttMFGAN) and compared with AttGAN, and separate AttGAN for multi-frequency bands denoising (AttGAN-MF).The multi-frequency FD and LD projections of 35, 5 and 10 patients were paired for training, validation and testing. The LD projections to be tested were separated to multi-frequency components and input to corresponding networks to get the denoised components, which were summed to get the final denoised projections. Voxel-based error indices were measured on the cardiac region on the reconstructed images. The perfusion defect size (PDS) was also analyzed. RESULTS: AttGAN-MF and AttMFGAN have superior performance on all physical and clinical indices as compared to conventional AttGAN. The integrated AttMFGAN is better than AttGAN-MF. Multi-frequency denoising with two frequency bands have generally better results than corresponding three-frequency bands methods. CONCLUSIONS: AttGAN-MF and AttMFGAN are promising to further improve LD MP SPECT denoising.

BRCA genetic testing and counseling in breast cancer: how do we meet our patients' needs?

BRCA1 and BRCA2 are tumor suppressor genes that have been linked to inherited susceptibility of breast cancer. Germline BRCA1/2 pathogenic or likely pathogenic variants (gBRCAm) are clinically relevant for treatment selection in breast cancer because they confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. BRCA1/2 mutation status may also impact decisions on other systemic therapies, risk-reducing measures, and choice of surgery. Consequently, demand for gBRCAm testing has increased. Several barriers to genetic testing exist, including limited access to testing facilities, trained counselors, and psychosocial support, as well as the financial burden of testing. Here, we describe current implications of gBRCAm testing for patients with breast cancer, summarize current approaches to gBRCAm testing, provide potential solutions to support wider adoption of mainstreaming testing practices, and consider future directions of testing.

Luteolin Inhibits Indoxyl Sulfate-Induced ICAM-1 and MCP-1 Expression by Inducing HO-1 Expression in EA.hy926 Human Endothelial Cells.

In patients with chronic kidney disease, the uremic toxin indoxyl sulfate (IS) accelerates kidney damage and the progression of cardiovascular disease. IS may contribute to vascular diseases by inducing inflammation in endothelial cells. Luteolin has documented antioxidant and anti-inflammatory properties. This study aimed to investigate the effect of luteolin on IS-mediated reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM-1) and monocyte chemoattractant protein (MCP-1) expression in EA.hy926 cells and the possible mechanisms involved. IS significantly induced ROS production (by 6.03-fold, p < 0.05), ICAM-1 (by 2.19-fold, p < 0.05) and MCP-1 protein expression (by 2.18-fold, p < 0.05), and HL-60 cell adhesion (by 31%, p < 0.05), whereas, luteolin significantly decreased IS-induced ROS production, ICAM-1 and MCP-1 protein expression, and HL-60 cell adhesion. Moreover, luteolin attenuated IS-induced nuclear accumulation of p65 and c-jun. Luteolin dose-dependently increased heme oxygenase-1 (HO-1) expression and the maximum fold induction of HO-1 by luteolin was 3.68-fold (p < 0.05), whereas, HO-1 knockdown abolished the suppression of ICAM-1 and MCP-1 expression by luteolin. Luteolin may protect against IS-induced vessel damage by inducing HO-1 expression in vascular endothelial cells, which suppresses nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) mediated ICAM-1 and MCP-1 expression.

WNT1-inducible signaling pathway protein 1 activation through C-X-C motif chemokine ligand 5/C-X-C chemokine receptor type 2/leukemia inhibitory factor/leukemia inhibitory factor receptor signaling promotes immunosuppression and neuroendocrine differentiation in prostate cancer.

The interaction between prostate cancer (PCa) cells and prostate stromal cells fosters an immunosuppressive tumor microenvironment (TME) that promotes tumor growth and immune evasion. However, the specific signaling pathways involved remain unclear. We identified a key mechanism involving the CXCL5/CXCR2 and LIF/LIFR pathways, which create a feedforward loop that enhances neuroendocrine differentiation (NED) in PCa cells and upregulates WNT1-inducible signaling pathway protein 1 (WISP1) in both cell types. WISP1 upregulation is essential for inducing immune checkpoints and immunosuppressive cytokines via LIF/LIFR signaling and STAT3 phosphorylation. This process leads to increased neuroendocrine markers, immune checkpoints, cell proliferation, and migration. Notably, WISP1 levels in patient sera correlate with PCa progression, suggesting its potential as a biomarker. Our findings elucidate the mechanisms by which reciprocal communication between PCa cells and stromal cells contributes to the formation of an immunosuppressive TME, driving the malignant progression of PCa and highlighting potential targets for therapeutic intervention.

Transurethral Resection of the Prostate (TURP) and concomitant inguinal hernioplasty: a single-center experience.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent condition in aging males, leading to bladder outlet obstruction (BOO) and associated urinary symptoms. With increasing life expectancy, the incidence of BPH and its co-morbidities, like inguinal hernia, has risen. This study explores the efficacy of combining transurethral resection of the prostate (TURP) and inguinal hernioplasty in a single surgical session to address both conditions, potentially reducing the need for multiple hospitalizations and surgical interventions. METHODS: This retrospective study at Chi Mei Medical Center included patients from 2014 to 2023 who underwent concurrent TURP and inguinal hernioplasty. A total of 85 patients met the criteria defined for this study. Preoperative, intraoperative, and postoperative characteristics were meticulously documented. Outcomes evaluated included the duration of the surgery, incidence of intraoperative and postoperative complications, duration of Foley catheterization, length of hospital stay, and treatment efficacy. Additionally, we conducted a comparative assessment of the surgical outcomes between two distinct techniques for inguinal hernia repair: open hernioplasty and laparoscopic hernioplasty (LH). RESULTS: In 85 patients who met the criteria, the mean age was 71.1 ± 7.8 years. The study reported no significant intraoperative complications, and postoperative care was focused on monitoring for blood loss, infection, and managing pain. The average postoperative hospital stay was 2.9 ± 1.0 days and the mean duration of catheterization was 51.6 ± 16.7 h, with a minimal complication rate observed during the one-year follow-up. A significant reduction in both operative duration and catheterization interval was observed in patients undergoing LH as opposed to those receiving open hernioplasty. CONCLUSION: Concurrent TURP and inguinal hernioplasty effectively manage BOO due to BPH and inguinal hernias with minimal complications, suggesting a viable approach to reducing hospital stays and surgical interventions. Laparoscopic techniques, in particular, offer benefits in operative efficiency and recovery time, making combined surgery a feasible option for selected patients.

Tomato NADPH oxidase SlWfi1 interacts with the effector protein RipBJ of Ralstonia solanacearum to mediate host defence.

Reactive oxygen species (ROS) play a crucial role in regulating numerous functions in organisms. Among the key regulators of ROS production are NADPH oxidases, primarily referred to as respiratory burst oxidase homologues (RBOHs). However, our understanding of whether and how pathogens directly target RBOHs has been limited. In this study, we revealed that the effector protein RipBJ, originating from the phytopathogenic bacterium Ralstonia solanacearum, was present in low- to medium-virulence strains but absent in high-virulence strains. Functional genetic assays demonstrated that the expression of ripBJ led to a reduction in bacterial infection. In the plant, RipBJ expression triggered plant cell death and the accumulation of H2O2, while also enhancing host defence against R. solanacearum by modulating multiple defence signalling pathways. Through protein interaction and functional studies, we demonstrated that RipBJ was associated with the plant's plasma membrane and interacted with the tomato RBOH known as SlWfi1, which contributed positively to RipBJ's effects on plants. Importantly, SlWfi1 expression was induced during the early stages following R. solanacearum infection and played a key role in defence against this bacterium. This research uncovers the plant RBOH as an interacting target of a pathogen's effector, providing valuable insights into the mechanisms of plant defence.

Prediction of In-Hospital Cardiac Arrest in the Intensive Care Unit: Machine Learning-Based Multimodal Approach.

Background: Early identification of impending in-hospital cardiac arrest (IHCA) improves clinical outcomes but remains elusive for practicing clinicians. Objective: We aimed to develop a multimodal machine learning algorithm based on ensemble techniques to predict the occurrence of IHCA. Methods: Our model was developed by the Multiparameter Intelligent Monitoring of Intensive Care (MIMIC)-IV database and validated in the Electronic Intensive Care Unit Collaborative Research Database (eICU-CRD). Baseline features consisting of patient demographics, presenting illness, and comorbidities were collected to train a random forest model. Next, vital signs were extracted to train a long short-term memory model. A support vector machine algorithm then stacked the results to form the final prediction model. Results: Of 23,909 patients in the MIMIC-IV database and 10,049 patients in the eICU-CRD database, 452 and 85 patients, respectively, had IHCA. At 13 hours in advance of an IHCA event, our algorithm had already demonstrated an area under the receiver operating characteristic curve of 0.85 (95% CI 0.815-0.885) in the MIMIC-IV database. External validation with the eICU-CRD and National Taiwan University Hospital databases also presented satisfactory results, showing area under the receiver operating characteristic curve values of 0.81 (95% CI 0.763-0.851) and 0.945 (95% CI 0.934-0.956), respectively. Conclusions: Using only vital signs and information available in the electronic medical record, our model demonstrates it is possible to detect a trajectory of clinical deterioration up to 13 hours in advance. This predictive tool, which has undergone external validation, could forewarn and help clinicians identify patients in need of assessment to improve their overall prognosis.

Steric and electronic influence on Cu-Cu short contacts in ß-thioketiminato tricopper(I) clusters.

A series of ß-thioketiminate copper(I) complex trimers [LCuI]3 were synthesized by modifying the ligand framework with electron-withdrawing groups (F and Cl) or electron-donating groups (iPr and Me) at the N-aryl ring as well as with CF3 groups on the chelating backbone. This ligand modification significantly impacts the enhancement of Cu⋯Cu short contacts, which can be rationalized by using steric and electronic factors of the chelated ligand. We observed that this intramolecular cuprophilicity among [LCuI]3 complexes is primarily governed by the size of N-aryl ortho-substituents. These findings were well supported by X-ray crystallography, Raman spectroscopy, and Mayer bond order analysis. The electronic effects induced by the ligand modification on the LCuI fragment were investigated using CO and 2,4,6-CNC6H2Me3 as probe molecules. Corroborated by the FTIR and CV measurements, our results reveal that the ß-thioketiminate SN chelators induce more pronounced changes in the electronic character of the LCuI fragment due to the presence of CF3 groups on the chelating backbone in comparison with the F or Cl substituents on the N-aryl ring.

Assessing the Clinical Effectiveness of an Exergame-Based Exercise Training Program Using Ring Fit Adventure to Prevent and Postpone Frailty and Sarcopenia Among Older Adults in Rural Long-Term Care Facilities: Randomized Controlled Trial.

BACKGROUND: Frailty and sarcopenia are geriatric syndromes of increasing concern and are associated with adverse health outcomes. They are more prevalent among long-term care facility (LTCF) users than among community dwellers. Exercise, especially multicomponent and progressive resistance training, is essential for managing these conditions. However, LTCFs, particularly in rural areas, face challenges in implementing structured exercise programs due to health care professional shortages. Moreover, older adults often become bored with repetitive exercise training and may lose interest over time. The Nintendo Switch Ring Fit Adventure (RFA) exergame is a novel exergame that combines resistance, aerobic, and balance exercises and offers a potential solution by boosting motivation in an immersive manner and reducing staff intervention needs. OBJECTIVE: We aimed to evaluate the clinical effectiveness of an exergame-based exercise training program delivered via RFA (exergame-RFA) in improving muscle mass and functional performance among older adult LTCF users. METHODS: This was a randomized controlled trial conducted from August 2022 to September 2023 and involved older adult LTCF users (aged ≥60 y) in rural southern Taiwan. Participants were randomized into an intervention group (exergame-RFA plus standard care) or a control group (standard care alone). The intervention, conducted seated with arm fit skills and trunk control exercises using the RFA, lasted 30 minutes twice weekly over 12 weeks. The primary outcomes measured were the Study of Osteoporotic Fractures index (serving as an indicator of frailty status) and the diagnostic criteria for sarcopenia (appendicular skeletal muscle mass index, handgrip strength, and gait speed). The secondary outcomes included functional performance (box and block test as well as maximum voluntary isometric contraction of the dominant upper extremity), muscle condition (muscle thickness measured using ultrasonography), activities of daily living (Kihon checklist), health-related quality of life (Short Form Health Survey-36), and cognitive function (brain health test). We used an intention-to-treat analysis, incorporating a simple imputation technique in statistical analysis. A mixed ANOVA, with time as a within-participant factor and intervention as a between-participant factor, was used to compare the training effects on outcomes. RESULTS: We recruited 96 individuals, of whom 60 (62%) underwent randomization. Of these 60 participants, 55 (92%) completed the study. Significant group×time interactions were observed in the intervention group in all primary outcomes (all P<.001, except P=.01 for handgrip strength) and most secondary outcomes, including maximum voluntary isometric contraction of the biceps (P=.004) and triceps brachii (P<.001) muscles, biceps muscle thickness measured using ultrasonography (P<.001), box and block test (P<.001), Kihon checklist (physical function: P=.01, mood status: P=.003, and total: P=.003), and brain health test (P<.001). CONCLUSIONS: The exergame-RFA intervention significantly improved muscle mass, strength, and functional performance among older adult users of rural LTCFs, offering a novel approach to addressing frailty and sarcopenia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05360667; https://clinicaltrials.gov/study/NCT05360667. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3389/fmed.2022.1071409.

RAB31 drives extracellular vesicle fusion and cancer-associated fibroblast formation leading to oxaliplatin resistance in colorectal cancer.

Epithelial-mesenchymal transition (EMT) is associated with tumorigenesis and drug resistance. The Rab superfamily of small G-proteins plays a role in regulating cell cytoskeleton and vesicle transport. However, it is not yet clear how the Rab family contributes to cancer progression by participating in EMT. By analysing various in silico datasets, we identified a statistically significant increase in RAB31 expression in the oxaliplatin-resistant group compared to that in the parental or other chemotherapy drug groups. Our findings highlight RAB31's powerful effect on colorectal cancer cell lines when compared with other family members. In a study that analysed multiple online meta-databases, RAB31 RNA levels were continually detected in colorectal tissue arrays. Additionally, RAB31 protein levels were correlated with various clinical parameters in clinical databases and were associated with negative prognoses for patients. RAB31 expression levels in all three probes were calculated using a computer algorithm and were found to be positively correlated with EMT scores. The expression of the epithelial-type marker CDH1 was suppressed in RAB31 overexpression models, whereas the expression of the mesenchymal-type markers SNAI1 and SNAI2 increased. Notably, RAB31-induced EMT and drug resistance are dependent on extracellular vesicle (EV) secretion. Interactome analysis confirmed that RAB31/AGR2 axis-mediated exocytosis was responsible for maintaining colorectal cell resistance to oxaliplatin. Our study concluded that RAB31 alters the sensitivity of oxaliplatin, a supplementary chemotherapy approach, and is an independent prognostic factor that can be used in the treatment of colorectal cancer.

Comprehensive genomic profiling and therapeutic implications for Taiwanese patients with treatment-naïve breast cancer.

BACKGROUND: Breast cancer is a heterogeneous disease categorized based on molecular characteristics, including hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression levels. The emergence of profiling technology has revealed multiple driver genomic alterations within each breast cancer subtype, serving as biomarkers to predict treatment outcomes. This study aimed to explore the genomic landscape of breast cancer in the Taiwanese population through comprehensive genomic profiling (CGP) and identify diagnostic and predictive biomarkers. METHODS: Targeted next-generation sequencing-based CGP was performed on 116 archived Taiwanese breast cancer specimens, assessing genomic alterations (GAs), including single nucleotide variants, copy number variants, fusion genes, tumor mutation burden (TMB), and microsatellite instability (MSI) status. Predictive variants for FDA-approved therapies were evaluated within each subtype. RESULTS: In the cohort, frequent mutations included PIK3CA (39.7%), TP53 (36.2%), KMT2C (9.5%), GATA3 (8.6%), and SF3B1 (6.9%). All subtypes had low TMB, with no MSI-H tumors. Among HR + HER2- patients, 42% (27/65) harbored activating PIK3CA mutations, implying potential sensitivity to PI3K inhibitors and resistance to endocrine therapies. HR + HER2- patients exhibited intrinsic hormonal resistance via FGFR1 gene gain/amplification (15%), exclusive of PI3K/AKT pathway alterations. Aberrations in the PI3K/AKT/mTOR and FGFR pathways were implicated in chemoresistance, with a 52.9% involvement in triple-negative breast cancer. In HER2+ tumors, 50% harbored GAs potentially conferring resistance to anti-HER2 therapies, including PIK3CA mutations (32%), MAP3K1 (2.9%), NF1 (2.9%), and copy number gain/amplification of FGFR1 (18%), FGFR3 (2.9%), EGFR (2.9%), and AKT2 (2.9%). CONCLUSION: This study presents CGP findings for treatment-naïve Taiwanese breast cancer, emphasizing its value in routine breast cancer management, disease classification, and treatment selection.

Binding of interleukin-1 receptor antagonist to cholinergic receptor muscarinic 4 promotes immunosuppression and neuroendocrine differentiation in prostate cancer.

The tumor microenvironment (TME) of prostate cancer (PCa) is characterized by high levels of immunosuppressive molecules, including cytokines and chemokines. This creates a hostile immune landscape that impedes effective immune responses. The interleukin-1 (IL-1) receptor antagonist (IL1RN), a key anti-inflammatory molecule, plays a significant role in suppressing IL-1-related immune and inflammatory responses. Our research investigates the oncogenic role of IL1RN in PCa, particularly its interactions with muscarinic acetylcholine receptor 4 (CHRM4), and its involvement in driving immunosuppressive pathways and M2-like macrophage polarization within the PCa TME. We demonstrate that following androgen deprivation therapy (ADT), the IL1RN-CHRM4 interaction in PCa activates the MAPK/AKT signaling pathway. This activation upregulates the transcription factors E2F1 and MYCN, stimulating IL1RN production and creating a positive feedback loop that increases CHRM4 abundance in both PCa cells and M2-like macrophages. This ADT-driven IL1RN/CHRM4 axis significantly enhances immune checkpoint markers associated with neuroendocrine differentiation and treatment-resistant outcomes. Higher serum IL1RN levels are associated with increased disease aggressiveness and M2-like macrophage markers in advanced PCa patients. Additionally, elevated IL1RN levels correlate with better clinical outcomes following immunotherapy. Clinical correlations between IL1RN and CHRM4 expression in advanced PCa patients and neuroendocrine PCa organoid models highlight their potential as therapeutic targets. Our data suggest that targeting the IL1RN/CHRM4 signaling could be a promising strategy for managing PCa progression and enhancing treatment responses.

PPAR-γ agonists reactivate the ALDOC-NR2F1 axis to enhance sensitivity to temozolomide and suppress glioblastoma progression.

Glioblastoma (GBM) is a type of brain cancer categorized as a high-grade glioma. GBM is characterized by limited treatment options, low patient survival rates, and abnormal serotonin metabolism. Previous studies have investigated the tumor suppressor function of aldolase C (ALDOC), a glycolytic enzyme in GBM. However, it is unclear how ALDOC regulates production of serotonin and its associated receptors, HTRs. In this study, we analyzed ALDOC mRNA levels and methylation status using sequencing data and in silico datasets. Furthermore, we investigated pathways, phenotypes, and drug effects using cell and mouse models. Our results suggest that loss of ALDOC function in GBM promotes tumor cell invasion and migration. We observed that hypermethylation, which results in loss of ALDOC expression, is associated with serotonin hypersecretion and the inhibition of PPAR-γ signaling. Using several omics datasets, we present evidence that ALDOC regulates serotonin levels and safeguards PPAR-γ against serotonin metabolism mediated by 5-HT, which leads to a reduction in PPAR-γ expression. PPAR-γ activation inhibits serotonin release by HTR and diminishes GBM tumor growth in our cellular and animal models. Importantly, research has demonstrated that PPAR-γ agonists prolong animal survival rates and increase the efficacy of temozolomide in an orthotopic brain model of GBM. The relationship and function of the ALDOC-PPAR-γ axis could serve as a potential prognostic indicator. Furthermore, PPAR-γ agonists offer a new treatment alternative for glioblastoma multiforme (GBM).

Luteolin, apigenin, and chrysin inhibit lipotoxicity-induced NLRP3 inflammasome activation and autophagy damage in macrophages by suppressing endoplasmic reticulum stress.

Lipotoxicity leads to numerous metabolic disorders such as nonalcoholic steatohepatitis. Luteolin, apigenin, and chrysin are three flavones with known antioxidant and anti-inflammatory properties, but whether they inhibit lipotoxicity-mediated NLRP3 inflammasome activation was unclear. To address this question, we used J774A.1 macrophages and Kupffer cells stimulated with 100 µM palmitate (PA) in the presence or absence of 20 µM of each flavone. PA increased p-PERK, p-IRE1α, p-JNK1/2, CHOP, and TXNIP as well as p62 and LC3-II expression and induced autophagic flux damage. Caspase-1 activation and IL-1ß release were also noted after 24 h of exposure to PA. In the presence of the PERK inhibitor GSK2656157, PA-induced CHOP and TXNIP expression and caspase-1 activation were mitigated. Compared with PA treatment alone, Bcl-2 coupled to beclin-1 was elevated and autophagy was reversed by the JNK inhibitor SP600125. With luteolin, apigenin, and chrysin treatment, PA-induced ROS production, ER stress, TXNIP expression, autophagic flux damage, and apoptosis were ameliorated. Moreover, TXNIP binding to NLRP3 and IL-1ß release in response to LPS/PA challenge were reduced. These results suggest that luteolin, apigenin, and chrysin protect hepatic macrophages against PA-induced NLRP3 inflammasome activation and autophagy damage by attenuating endoplasmic reticulum stress.

Clinicopathologic Features and Cytologic Correlation of ALK-Rearranged Papillary Thyroid Carcinoma: A Series of Eight Cases.

Anaplastic lymphoma kinase (ALK) gene fusions are rare in papillary thyroid carcinoma (PTC) but may serve as a therapeutic target. This study aims to evaluate the preoperative cytologic findings and clinicopathologic features of a series of eight ALK-rearranged PTCs from our pathology archives and consultations. All cases were confirmed by ALK D5F3 immunohistochemistry and six with additional targeted RNA-based next-generation sequencing (NGS). The original fine-needle aspiration (FNA) cytology diagnosis included the Bethesda System (TBS) category II in three (37.5%), TBS III in two (25%), TBS V in two (25%), and TBS VI in one (12.5%). Six cases had available FNA cytology and were reviewed. The cytologic features showed microfollicular architecture as well as limited or reduced nuclear elongation and chromatin alterations in all six. Nuclear grooves and pseudoinclusions were absent in two cases, rarely or focally noted in three, and frequently found in one. Two cases initially diagnosed as TBS II, showing microfollicular architecture without well-developed nuclear features, were revised to TBS III (with architectural atypia only). For histologic correlations, four were infiltrative follicular variant PTCs, three as classic subtype PTC with predominant follicular growth, and one as solid/trabecular subtype PTC. All eight cases demonstrated reduced PTC nuclear features with respect to nuclear elongation and chromatin alterations compared to those typically identified in "BRAF-like" PTCs. The NGS testing revealed EML4::ALK fusion in three, STRN::ALK fusion in two, and ITSN2::ALK fusion in one. In conclusion, although ALK-rearranged PTCs have been associated with neutral gene expression profile from a BRAF-RAS scoring perspective, the "RAS-like" nuclear features were more commonly identified in this series, resulting in frequent indeterminate diagnosis of preoperative FNA.

FluoroFusion: NHC-Catalyzed Nucleophilic Aromatic Substitution Reaction Unveils Functional Perfluorinated Diarylmethanones.

A mild, facile, and metal-free approach via the N-heterocyclic carbene-catalyzed SNAr reaction between aryl aldehydes with perfluoroarenes to obtain the coveted functional perfluorinated diarylmethanones is disclosed. This method accommodates a diverse substrate range and exhibits notable tolerance toward various functional groups. Our success in modifying biologically relevant molecules, crafting a fully fluorinated bioisosteric analogue of drug candidate D1, and highlighting the potential of these ketones as valuable electrolyte additives for lithium-ion batteries (LIBs) underscores the versatility of our methodology.

Base-promoted triple cleavage of CCl2Br: a direct one-pot synthesis of unsymmetrical oxalamide derivatives.

We present a novel, eco-friendly and one-pot approach for synthesizing unsymmetrical oxalamides with the aid of dichloroacetamide and amine/amides in the presence of CBr4 in a basic medium. The use of water as a potent supplement for the oxygen atom source and the detailed mechanism have been disclosed. Moreover, the protocol involves triple cleavage of CCl2Br and the formation of new C-O/C-N bonds, with the advantage of achieving selective bromination using CBr4 with good to excellent yield under mild conditions. The method also demonstrates promise for industrial use, as proven by its effective implementation in gram-scale synthesis conducted in a batch process, along with its utilization in a continuous-flow system.

NIMBYism and Strategies for Coping with Managing Protests during the Establishment of Community Mental Health Facilities in Taiwan: Insights from Frontline Healthcare Professionals.

Taiwanese community mental health facilities encounter opposition/resistance from residents, commonly known as "Not-In-My-Backyard" (NIMBYism). This study investigated NIMBYism during the establishment of such facilities and how they respond to such resistance. A qualitative study through semi-structured interviews was used to obtain purposively sampled data. Fifteen frontline healthcare professionals from community mental health facilities in Taiwan were interviewed individually, using an organizational analysis structure. Data were analyzed using qualitative content analysis. Two themes: "Reasons for Resident Resistance" and "Institutional Response Strategies", two categories, and 11 subcategories emerged. The findings demonstrated the following: (1) Reasons behind residents' resistance toward establishing community mental health facilities are diverse. (2) Communities lack understanding regarding people with mental disorders, leading to irrational beliefs. (3) Fear and negative perceptions toward people with mental disorders exist. (4) Strategies employed by the facilities include providing community services to foster amicable relationships, organizing community outreaches, training people with mental disorders within communities, nurturing neighborhood connections, establishing and sustaining friendships within communities, inviting residents to visit community mental health facilities or introducing the facilities to communities, and leveraging governmental support. The government should adopt regulations or laws to reduce discrimination, promote human rights, and legislate to demarcate the use of community land.

Do hospitals attaining a public recognition for treating nurses fairly deliver better-quality health care? Evidence from cross-sectional analysis of California hospitals.

AIM: This study explored whether hospitals that allocate greater resources to their nursing staff provide better healthcare services than those that invest less in their nursing personnel. DESIGN: Cross-sectional logistic and tobit analyses. METHODS: We examined a sample of 314 California hospitals in 2017. We obtained a hospital's public recognition for treating nurses fairly between 2015 and 2017 from Nurse.org, the largest online community of nurses. We derived a hospital's healthcare quality in 2018 from the 2019-2020 Best Hospitals rankings released by U.S. News, a well-known media company publishing independent healthcare assessments periodically. RESULTS: Our results showed that a nurse-friendly workplace was a crucial determinant of its overall healthcare quality. CONCLUSION AND IMPLICATIONS: Healthcare administrators keen to enhance the quality of healthcare services should consider creating nurse-friendly workplaces. Furthermore, their evaluation of nurses' contributions to overall healthcare quality should not solely depend on the nurse-assessed quality of care, but rather comprise not only broad aspects of patient outcomes in primary care but also patient experiences, care-related factors and expert opinions. PATIENT OR PUBLIC CONTRIBUTION: Our study helped address the overwhelmed healthcare system, whose long-running shortage of nurses has been exacerbated by the COVID-19 pandemic. Our work suggested that a hospital's investment in a nurse-friendly workplace can enhance its acquisition, retention and devotion of the nursing staff. This, in turn, can have profound impacts on its overall healthcare quality. WHAT ALREADY IS KNOWN: Existing empirical evidence on the relation between nurse-friendly workplace and healthcare quality is limited and inconclusive. WHAT THIS PAPER ADDS: We documented evidence that the quality of healthcare services provided by hospitals varies with their treatment of nursing staff. IMPLICATIONS FOR PRACTICE/POLICY: Our results provided insights into key policies that have the potential to improve healthcare quality.