Exploring Physicians' Perceptions of Digital Health's Impact on the Patient-Physician Relationship in the Primary Health Care Setting: Qualitative Descriptive Study.

BACKGROUND: Digital health has become essential for effective clinical practice. However, the successful adoption of digital health is dependent on the strength of the patient-physician relationship. The patient-physician relationship shapes the quality of care and impacts health care outcomes, especially in primary care. However, the impact of the increasing use of digital health on the patient-physician relationship is uncertain. OBJECTIVE: This study aims to explore the types of digital health primary care physicians use and understand their impact on the patient-physician relationship from their perspective. METHODS: This exploratory qualitative descriptive study used individual in-depth interviews guided by a semistructured topic guide. We purposively sampled physicians from 6 general primary care clinics in Singapore and used thematic analysis to identify emergent themes. RESULTS: We conducted 12 interviews. We found that primary care physicians in Singapore had minimal exposure to digital health beyond the scope of institutional implementation. The three key themes that emerged were as follows: (1) evolving roles of both physicians and patients; (2) impact on trust, knowledge acquisition, and longitudinal care; and (3) adoption and use factors of digital health impacting patient-physician relationships. The adoption and use factors comprised "social and personal," "technical and material," and "organization and policy" factors. CONCLUSIONS: The study identified that, while primary care physicians held mostly positive views on adopting digital health in improving the patient-physician relationship, they were concerned that digital health might erode trust, hinder proper knowledge acquisition, and reduce humanistic interaction. These concerns called for a nuanced approach to ensure that digital health would not compromise the patient-physician relationship. This could be achieved by ensuring that physicians possess the necessary skills, knowledge, and positive attitude, while health care organizations would provide robust IT capabilities and support. We recommend that education be refined and government policies on digital health adoption and use be revised to align with the goal of strengthening the patient-physician relationship.

Bufalin: A promising therapeutic drug against the cisplatin-resistance of ovarian cancer by targeting the USP36/c-Myc axis.

Cisplatin (DPP) resistance is a severe obstacle to ovarian cancer (OC) treatment. Our research aims to uncover the therapeutic effect and the underlying mechanism of Bufalin against DDP resistance. The cell viability, proliferation capacity, γH2AX expression, and apoptosis ratio were quantified via CCK8 assay, colony formation assay, immunofluorescence, and flow cytometry analysis respectively. Xenografting experiment was performed to detect the tumor growth. Molecular docking was applied to mimic the combination of Bufalin and USP36 protein, and Western blotting was conducted to measure the Bax, Bcl-2, γH2AX, USP36, and c-Myc expression. The c-Myc ubiquitination and half-life were detected via ubiquitination assay and cycloheximide chasing assay. Bufalin treatment notably suppressed the cell viability and colony numbers, and increased the apoptosis ratio and γH2AX level in the DDP treatment group. Bufalin therapy also notably inhibited tumor growth, Bax, Bcl-2, and γH2AX expression in vivo. Moreover, the Bufalin application remarkedly reduced the c-Myc expression and half-life and increased the c-Myc ubiquitination via interaction and subsequent down-regulation of USP36. Knockdown of USP36 reversed the antiproliferative effect and proapoptotic capacity of Bufalin therapy in the DDP treatment group. In conclusion, Bufalin can overcome the DDP resistance in vitro and in vivo via the USP36/c-Myc axis, which innovatively suggests the therapeutic potential of Bufalin against DDP resistance ovarian cancer.

Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the primary form of lung cancer, and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease. However, the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies. Consequently, it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments. AIM: To identify the metabolic signatures associated with neutrophil extracellular traps (NETs) and chemoimmunotherapy efficacy in NSCLC patients. METHODS: In total, 159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled. We first investigated the characteristics influencing clinical efficacy. Circulating levels of NETs and cytokines were measured by commercial kits. Liquid chromatography tandem mass spectrometry quantified plasma metabolites, and differential metabolites were identified. Least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest algorithms were employed. By using plasma metabolic profiles and machine learning algorithms, predictive metabolic signatures were established. RESULTS: First, the levels of circulating interleukin-8, neutrophil-to-lymphocyte ratio, and NETs were closely related to poor efficacy of first-line chemoimmunotherapy. Patients were classed into a low NET group or a high NET group. A total of 54 differential plasma metabolites were identified. These metabolites were primarily involved in arachidonic acid and purine metabolism. Three key metabolites were identified as crucial variables, including 8,9-epoxyeicosatrienoic acid, L-malate, and bis(monoacylglycerol)phosphate (18:1/16:0). Using metabolomic sequencing data and machine learning methods, key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy. CONCLUSION: The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.

Operando Electrodeposition of Nonprecious Metal Copper Nanocatalysts on Low-Dimensional Support Materials for Nitrate Reduction Reactions.

Supported nonprecious metal catalysts such as copper (Cu) are promising replacements for Pt-based catalysts for a wide range of energy-related electrochemical reactions. Direct electrochemical deposition is one of the most straightforward and versatile methods to synthesize supported nonprecious metal catalysts. However, further advancement in the design of supported nonprecious metal catalysts requires a detailed mechanistic understanding of the interplay between kinetics and thermodynamics of the deposition phenomena under realistic reaction conditions. Here, we study the electrodeposition of Cu on carbon nanotubes and graphene derivatives under electrochemical conditions using in situ liquid cell transmission electron microscopy (TEM). By combining real-time imaging, electrochemical measurements, X-ray photoelectron spectroscopy (XPS), and finite-element analysis (FEA), we show that low-dimensional support materials, especially carbon nanotubes, are excellent for generating uniform and finely dispersed platinum group metal-(PGM)-free catalysts under mild electrochemical conditions. The electrodeposited Cu on graphene and carbon nanotubes is also observed to show good electrochemical activity toward nitrate reduction reactions (NO3RRs), further supported by density functional theory (DFT) calculations. Nitrogen doping plays an important role in guiding nonprecious metal deposition, but its low electrical conductivity may give rise to lower NO3RR activity compared to its nondoped analogue. The development of supported nonprecious metals through interfacial and surface engineering for the design of supported catalysts will substantially reduce the demand for precious metals and generate robust catalysts with better durability, thereby presenting opportunities for solving the critical problems in energy storage and electrocatalysis.

Impact of red blood cell distribution width (RDW) on postoperative outcomes in hepatocellular carcinoma (HCC) patients.

This study examines the relationship between red blood cell distribution width (RDW) and the prognosis of patients undergoing hepatectomy for hepatocellular carcinoma (HCC). Additionally, it explores the potential effect of RDW for the early identification of high-risk patients after surgery, advocating for timely interventions to improve outcomes. A comprehensive literature search was conducted on May 16, 2022, across PubMed (23 studies), Embase (45 studies), the Cochrane Library (1 study), and CNKI (17 studies), resulting in 6 relevant articles after screening. This analysis primarily focused on the postoperative outcomes of patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to assess prognosis, with survival indicators including overall survival (OS) and disease-free survival (DFS). All 6 studies reported on OS, and 2 addressed DFS. A total of 1645 patients from 6 studies were included. The pooled analysis revealed that RDW is an independent prognostic factor for both OS (HR = 1.50, I²â€…= 84%, 95% CI = 1.23-1.77, P < .01) and DFS (HR = 2.06, I²â€…= 15%, 95% CI = 1.51-2.82, P < .01). Patients in the high RDW group exhibited significantly poorer OS and DFS compared to those in the low RDW group. RDW is a prognostic factor for HCC patients after surgery. Elevated RDW levels are associated with a poorer prognosis, adversely affecting both OS and DFS. RDW may serve as a valuable marker for stratifying risk and guiding intervention strategies in the postoperative management of HCC patients.

Experiences of living with overweight/obesity and early type 2 diabetes in Singapore-a qualitative interview study.

OBJECTIVES: To understand the lived experience of adults with overweight/obesity and early type 2 diabetes in a modern urban environment, and the interrelations among the various aspects of these experiences and participants' attitudes to weight management. DESIGN: Qualitative inductive approach to analysing data thematically from semistructured interviews and interpreted from a socioecological perspective. SETTING: Primary care clinics located in northern and central Singapore. PARTICIPANTS: 21 patients between 29 and 59 years old who are living with overweight/obese (Body Mass Index of 25.3-44.0kg/m2) and type 2 diabetes for 6 years or less. RESULTS: The main themes - everyday life, people around me and within me - pointed to a combination of barriers to weight and health management for participants. These included environmental factors such as easy physical and digital access to unhealthy food, and high-stress work environments; social factors such as ambiguous family support and dietary practices of peers; and individual factors such as challenges with self-regulation, prioritising work, dealing with co-existing medical conditions and the emotional significance of food. While lack of motivation and cultural dietary practices are hard to change, a problem-solving attitude, and presence of role models, may enable behaviour change. CONCLUSION: An exploration of the lifeworld of patients with overweight/obese and early type 2 diabetes revealed that work demands, dietary practices in the workplace and at home, and the easy availability of calorie-dense foods afforded by a technology-infused environment hindered the individual's efforts at maintaining a healthy weight and lifestyle. Policy and initiatives promoting work-life balance as well as individualised interventions can support participants' stress management, and problem-solving capability for behaviour change. These barriers stemmed from the various domains of the environmental, interpersonal and intrapersonal but were interrelated. They underscored the need for an integrated approach to weight and diabetes management.

Omaveloxolone Prevents Polystyrene Microplastic-Induced Ovarian Granulosa Cell Apoptosis via the Keap1/Nrf2/HO-1 Pathway in Rats.

Microplastics (MPs) are persistent environmental pollutants that enter the circulatory system and subsequently reduce sperm quantity and quality. However, the influence of polystyrene MPs (PS-MPs) on the ovary and relevant mechanisms remain elusive. Herein, we aimed to examine the impact of PS-MPs on oxidative disorders in ovarian tissues and elucidate the underlying mechanisms. Healthy female rats were treated with different concentrations of 0.5 µm PS-MPs (diluted in deionized H2O) for 90 days. Upon examination of hematoxylin-eosin-stained ovarian tissue sections, the number of growing follicles was reduced in PS-MP-treated rats when compared with that in control rats. Enzyme-linked immunosorbent assays revealed that PS-MP exposure markedly reduced anti-Müllerian hormone (AMH) levels. Treatment with PS-MPs downregulated superoxide dismutase, glutathione, and catalase activities in ovarian tissues while upregulating malondialdehyde levels. Furthermore, exposure to PS-MP blocked the Keap1/Nrf2/HO-1 signal transduction pathway. PS-MPs also triggered apoptosis in the ovarian tissue, as evidenced by increased TUNEL staining and expression levels of cleaved caspase-9, Bax, and Bcl-2. To reactivate the Keap1/Nrf2/HO-1 pathway, rats were co-administered PS-MPs and omaveloxolone (Oma), an Nrf2 activator, for 1 week. We found that Oma could counteract the PS-MP-mediated effects on oxidative disorder, apoptosis, AMH production, and follicle number in rat ovarian tissues. To develop an in vitro model, granulosa cells (GCs) were treated with 10 µM H2O2 for 12 h to induce oxidative stress. H2O2-stimulated GCs exhibited attenuated cell growth and upregulated apoptosis and oxidative stress. Oma administration could ameliorate the H2O2-induced effects in terms of regulating cell viability, apoptosis, and oxidative stress in GCs. In summary, PS-MPs could induce apoptosis and oxidative stress via the Keap1/Nrf2/HO-1 signaling pathway in both rats and GCs.

Prevalence of vitamin D insufficiency in early pregnancies- a Singapore study.

Vitamin D plays an essential role in bone and mineral metabolism. There is increased interest in understanding prevalence of Vitamin D deficiency in pregnancy as many studies report association of low vitamin D levels with obstetric complications and neonatal sequelae. There is a paucity of studies in Singapore evaluating levels of vitamin D levels during the first trimester of pregnancies. We aim to study the prevalence of vitamin D insufficiency in this population. Our study assessed vitamin D levels in these women. Vitamin D (Plasma 25(OH)D concentration) levels in multiracial women during the first trimester were collected via venepuncture at their booking antenatal visit. They were stratified into sufficient ≥30ng/ml, insufficient ≥20ng/ml and <30ng/ml, moderately deficient ≥10ng/ml and <20ng/ml and severely deficient <10ng/ml. 93 women were included in this study. Only 2.2% of our study population had sufficient vitamin D levels. In women who had insufficient levels, the heavier the weight, the more likely to be vitamin D deficient. Interestingly, we also note that the older the patient, the less likely they are to be deficient. In women with periconceptual multivitamin supplementation, the average vitamin D level for those with supplementation was 2.10ng/ml higher than those without. Majority of patients were recruited from a single study member's patient pool who were mostly Chinese. Prevalence of Vitamin D deficiency in general obstetric patients with higher BMI and darker skinned patients may be even lower in Singapore. The high prevalence of Vitamin D insufficiency in our patients prove that it is a prominent problem in our population. We aim to implement screening of vitamin D levels as part of antenatal investigations in the first trimester and recommend supplementation as required. We also hope to evaluate the association of low vitamin D levels with obstetric or neonatal complications further understanding its implications.

Malformations of cortical development: Fetal imaging and genetics.

BACKGROUND: Malformations of cortical development (MCD) are a group of congenital disorders characterized by structural abnormalities in the brain cortex. The clinical manifestations include refractory epilepsy, mental retardation, and cognitive impairment. Genetic factors play a key role in the etiology of MCD. Currently, there is no curative treatment for MCD. Phenotypes such as epilepsy and cerebral palsy cannot be observed in the fetus. Therefore, the diagnosis of MCD is typically based on fetal brain magnetic resonance imaging (MRI), ultrasound, or genetic testing. The recent advances in neuroimaging have enabled the in-utero diagnosis of MCD using fetal ultrasound or MRI. METHODS: The present study retrospectively reviewed 32 cases of fetal MCD diagnosed by ultrasound or MRI. Then, the chromosome karyotype analysis, single nucleotide polymorphism array or copy number variation sequencing, and whole-exome sequencing (WES) findings were presented. RESULTS: Pathogenic copy number variants (CNVs) or single-nucleotide variants (SNVs) were detected in 22 fetuses (three pathogenic CNVs [9.4%, 3/32] and 19 SNVs [59.4%, 19/32]), corresponding to a total detection rate of 68.8% (22/32). CONCLUSION: The results suggest that genetic testing, especially WES, should be performed for fetal MCD, in order to evaluate the outcomes and prognosis, and predict the risk of recurrence in future pregnancies.

Total flavonoids of Astragalus protects glomerular filtration barrier in diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a prevalent complication of diabetes and the leading cause of end-stage renal disease. Recent evidence suggests that total flavonoids of Astragalus (TFA) has promising effects on diabetes; however, its influence on DKD and the underlying mechanism remains unclear. METHODS: In this study, we induced the DKD model using streptozotocin (STZ) in male C57BL/6J mice and utilized glomerular endothelial cell (GEC) lines for in vitro investigations. We constructed a network pharmacology analysis to understand the mechanism of TFA in DKD. The mechanism of TFA action on DKD was investigated through Western blot analysis and multi-immunological methods. RESULTS: Our findings revealed that TFA significantly reduced levels of urinary albumin (ALB). Network pharmacology and intracellular pathway experiments indicated the crucial involvement of the PI3K/AKT signaling pathway in mediating these effects. In vitro experiments showed that TFA can preserve the integrity of the glomerular filtration barrier by inhibiting the expression of inflammatory factors TNF-alpha and IL-8, reducing oxidative stress. CONCLUSION: Our findings demonstrated that TFA can ameliorates the progression of DKD by ameliorating renal fibrosis and preserving the integrity of the kidney filtration barrier. These results provide pharmacological evidence supporting the use of TFA in the treatment of kidney diseases.

Functionalized MXene Films with Substantially Improved Low-Voltage Actuation.

Ti3 C2 Tx MXene film is promising for low-voltage electrochemical actuators (ECAs) due to its excellent electrical conductivity, volumetric capacitance, and mechanical properties. However, its in-plane actuation is limited to little intralayer strain of MXene sheets under polarization. Here it is demonstrated that a simple tetrabutylammonium (TBA) functionalization of MXene improves the in-plane actuation strain by 337% and also enhances the mechanical property and stability in air and the electrolyte. Various in situ characterizations reveal that the improved actuation is ascribed to the co-insertion/desertion of TBA and Li ions into/from MXene interlayer galleries and inter-edge gaps that causes a large in-plane sliding of MXene sheets under negative/positive polarizations. The assembled bending actuator has a high strength and modulus and generates a peak-to-peak strain difference of 0.771% and a blocking force up to 51.5 times its own weight under 1 V. The designed soft robotic tweezer can grasp an object under 1 V and hold it firmly under 0 V. The novel sheet sliding mechanism resembling the filament sliding theory in skeletal muscles may inspire the design of high-performance actuators with other nanomaterials.

The Odorant-Binding Protein 1 Mediates the Foraging Behavior of Grapholita molesta Larvae.

Since eggs are laid directly on fruit skin, it is typically believed that food odor has little impact on the foraging of Grapholita molesta larvae. It is crucial to note that larvae that hatch on twigs and leaves could need some sort of identification system when foraging. Here, 22 GmolOBP genes were identified from the G. molesta larval transcriptome via the comparison of conserved domain and homology in the protein level. GmolOBP1 had strong affinities for important pear-fruit volatiles, which caused larvae strong behavioral responses. However, after GmolOBP1 silencing, the larvae lost their attraction to methyl salicylate, α-farnesene, butyl acetate, ethyl butanoate, and ethyl hexanoate, and the effects of larvae seeking various pears were significantly reduced. Consequently, GmolOBP1 was required for the reception of pear volatiles and was involved in mediating how G. molesta larvae foraged. Our research revealed the GmolOBP1 foraging signal recognition mechanism as well as potential molecular targets for field pest management.

Construction of monocyte-related prognosis model based on comprehensive analysis of bulk RNA-seq and single-cell RNA-seq in high-grade serous ovarian cancer.

High-grade serous ovarian cancer (HGSOC) is a common subtype of ovarian cancer with high mortality. Finding a new biomarker is useful for the diagnosis and treatment of HGSOC. The scRNA and bulk RNA data were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. The monocyte-related clusters were identified and annotated by Seruat and SingleR package. The Kaplan-Meier and receiver operating characteristic curve was used to determine the prognosis. The differentially expressed genes were determined by limma. The single sample Gene Set Enrichment Analysis, Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes were used for the enrichment function. The correlation between drug activity and gene expression was assessed by rcellminer and rcellminer Data package. We identified 9 cell types and obtained 37 differentially expressed marker genes of monocyte. A2M, CD163, and FPR1 were screened out as hub genes and used to construct risk model in HGSOC through univariate and multivariate cox analysis. Single sample Gene Set Enrichment Analysis showed risk score was related to B cell and T cell signal pathways, and further analysis showed most immune checkpoint genes expressions were upregulated in high-risk score group. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis exhibited that hub gene related genes were involved in signal receptor binding and cytokine-cytokine interaction. Low A2M expression and high expression of CD163 and FPR1 were associated with poor prognosis. Gene Set Enrichment Analysis revealed that A2M promoted tumor development through enhancing immune cell related signal pathways, while CD163 and FPR1 inhibited tumor development through activated carcinogenic signal pathways. Drug sensitivity analysis revealed that these hub genes could be potential therapeutic targets for the treatment of HGSOC. We constructed a risk model for the overall survival and explored the potential mechanism of monocyte in HGSOC.

Prevalence and management outcomes of tonic tensor tympani syndrome in an ENT audiology tinnitus clinic in Singapore.

OBJECTIVE: Tonic tensor tympani syndrome is found in a subset of tinnitus patients who experience intra-aural and peri-aural symptoms, in addition to their tinnitus, in the absence of clinically detectable pathology. As the syndrome has not been widely reported, this study aims to determine its prevalence and evaluate the effectiveness of current management. METHODS: The tinnitus management clinic records of patients over the past six years were assessed to identify tonic tensor tympani syndrome patients and track their progress based on patient-reported Tinnitus Handicap Index scores. Patients with reversible ear pathology and temporomandibular joint disorder were excluded. RESULTS: It was found that 13 per cent of the tinnitus management patients fulfilled the criteria for tonic tensor tympani syndrome and 94 per cent of those who returned for follow up showed an improvement in their Tinnitus Handicap Index grades. CONCLUSION: This study suggests that tonic tensor tympani syndrome is a significant problem among tinnitus patients and current tinnitus management strategies contribute effectively to helping such patients habituate to their symptoms.

Hypoxic tumour-derived exosomal miR-1225-5p regulates M2 macrophage polarisation via toll-like receptor 2 to promote ovarian cancer progress.

Tumor-secreted exosomes are critical for the functional regulation of tumor-associated macrophages (TAMs). This study aimed to explore how exosomes secreted by ovarian carcinoma cells regulate the phenotype and function of macrophages. Hypoxic treatment of A2780 cells was postulated to mimic the tumor microenvironment, and exosomes were co-cultured with TAMs. miR-1225-5p was enriched in hypoxic exosomes and contributed to M2 macrophage polarizationby modulating Toll-like receptor 2 expression (TLR2). Furthermore, hypoxia-treated macrophages promote ovarian cancer cell viability, migration, and invasion via the wnt/ß-catenin pathway. This study clarified that exosomal miR-1225-5p promotes macrophage M2-like polarization by targeting TLR2 to promote ovarian cancer, which may via the wnt/ß-catenin pathway.

Interactions of CyMe4 -BTBP ligand with lanthanides and actinides: Insights from ESI-MS and DFT calculations.

Electrospray Ionization Mass Spectrometry (ESI-MS) technique and density functional theory (DFT) calculations were combined to study the formation of the complexes of lanthanides (Ln = La, Ce, Nd, Sm, Eu, Yb) and actinides (UO2 2+ , Th4+ ) with CyMe4 -BTBP (6,6'-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-benzo-[1,2,4-]triazin-3-yl)-[2,2']bipyridine) to understand the mechanisms during the extraction process. Mass spectrometry titrations showed the formation of the complexation in acetonitrile. For lanthanides, only 1:2 complexes ([Ln(L)2 ]3+ , [Ln(L)2 (CH3 CN)]3+ ), [Ln(L)2 (NO3 )]2+ ) were found at low [Ln]/[L] concentration ratios, whereas the 1:1 complexes ([Ln(L)(NO3 )2 ]+ ) were observed when the [Ln]/[L] concentration ratio reached 1.0. For uranyl complexes, 1:1 complex ([UO2 L(NO3 )]+ ) was the only species within the measuring range. Th4+ complexes had two compositions: 1:1 and 1:2, in which 1:2 species was the dominant complex. Collision-induced dissociation (CID) was employed to characterize the fragmentation process. The fragmentation process was unfolded sequentially on both sides of CyMe4 -BTBP ligand with the loss of alkyl groups and cleavage of triazinyl rings. The CID results of CyMe4 -BTBP complexes revealed a slight difference depending on the metal center. The DFT calculations showed that the stable complexes formed in acetonitrile solution were consistent with the ESI-MS results.

Identification of tumor immunophenotypes associated with immunotherapy response in bladder cancer.

OBJECTIVES: This study aims to reveal immunophenotypes associated with immunotherapy response in bladder cancer, identify the signature genes of immune subtypes, and provide new molecular targets for improving immunotherapy response. METHODS: Bladder cancer immunophenotypes were characterized in the bulk RNA sequencing dataset GSE32894 and Imvigor210, and gene expression signatures were established to identify the immunophenotypes. Expression of gene signatures were validated in single-cell RNA sequencing dataset GSE145140 and human proteins expression data source. Investigation of Immunotherapy Response was performed in IMvigor210 dataset. Prognosis of tumor immunophenotypes was further analyzed. RESULTS: Inflamed and immune-excluded immunophenotypes were characterized based on the tumor immune cell scores. Risk score models that were established rely on RNA sequencing profiles and overall survival of bladder cancer cohorts. The inflamed tumors had lower risk scores, and the low-risk tumors were more likely to respond to atezolizumab, receiving complete response/partial response (CR/PR). Patients who responded to atezolizumab had higher SRRM4 and lower NPHS1 and TMEM72 expression than the non-responders. SRRM4 expression was a protective factor for bladder cancer prognosis, while the NPHS1 and TMEM72 showed the opposite pattern. CONCLUSION: This study provided a novel classification method for tumor immunophenotypes. Bladder cancer immunophenotypes can predict the response to immune checkpoint blockade. The immunophenotypes can be identified by the expression of signature genes.

Clinical Characteristics, Drug Resistance, and Risk Factors for Death of Klebsiella pneumoniae Infection in Patients with Acute Pancreatitis: A Single-Center Retrospective Study from China.

Objective: Infection is a common complication of acute pancreatitis (AP). Klebsiella pneumoniae (KP) is one of the most common pathogens associated with nosocomial infections. Our study focuses on investigating the clinical characteristics and risk factors for death of Klebsiella pneumoniae infections in AP patients, further to quantify the prognosis of the patients, and provide evidence for guiding antibiotic use and improving prognosis. Methods: The data of epidemiology, clinical manifestations and drug resistance rate with K. pneumoniae infections in AP patients from January 1, 2012 to August 30, 2022 were retrospectively collected. Logistic regression model and Cox regression model were, respectively, used to determine the risk factors for carbapenem-resistant Klebsiella pneumoniae (CRKP) acquisition and death. The nomogram prediction model was built by RMS software package to predict the 90-day survival rate. Results: One hundred and twenty-six AP patients combined with K. pneumoniae infections, with a mortality rate of 34.9%. The most common infection sites were pancreas and peri-pancreas (54.8%), followed by lung (20.6%) and blood stream (18.3%). The resistance rate of K. pneumoniae to commonly used antibiotics in clinical practice was high, especially CRKP, which was only sensitive to sulfamethoxazole-trimethoprim (SMZ-TMP) and tigecycline (TGC) (resistance rates were 37.57% and 17.57%, respectively). Independent risk factors for CPKP acquisition were male (OR = 1.655, 95% CI 0.642-4.265, P = 0.017) and PICC/CVC implantation (OR = 3.157, 95% CI 1.223-8.147, P = 0.021). Independent risk factors for mortality included carbapenem resistance (HR = 2.556, 95% CI 1.011-6.462, P = 0.047), hemorrhage (HR = 2.392, 95% CI 1.104-5.182, P = 0.027), septic shock (HR = 3.022, 95% CI 1.312-6.959, P = 0.009), age >60 years (HR = 2.977, 95% CI 1.303-6.799, P = 0.01), creatinine >177µmol/L (HR = 2.815, 95% CI 1.075-7.369, P = 0.035). Conclusion: K. pneumoniae infection has become a serious threat for AP patients, which recommends us more attention and active new strategies seeking.