Factors Influencing Time From Diagnosis to Treatment of Breast Cancer and the Impact of Longer Waiting Time on Survival in Kathmandu Valley, Nepal: A Population-Based Study.

PURPOSE: Longer time between breast cancer (BC) diagnosis and treatment initiation is associated with poorer survival, and this may be a factor behind disparities in global survival rates. We assessed time to BC treatment in the Kathmandu Valley, Nepal, including factors associated with longer waiting times and their impact on survival. METHODS: We conducted a retrospective population-based study of BC cases recorded in the Kathmandu Valley Population-Based Cancer Registry between 2018 and 2019. Fieldwork survey through telephone was undertaken to collect additional sociodemographic and clinical information. Logistic regression was performed to identify factors associated with longer time to treatment, and Kaplan-Meier and Cox proportional hazard regression was used to examine survival time and evaluate the association between longer time to treatment and survival. RESULTS: Among the 385 patients with BC, one third waited >4 weeks from diagnosis to initial treatment. Lower education was associated with longer time to treatment (adjusted odds ratio, 1.63 [95% CI, 1.03 to 2.60]). The overall 3-year survival rate was 88.6% and survival was not associated with time to treatment (P = .50). However, advanced stage at diagnosis was associated with poorer survival (adjusted hazard ratio, 4.09 [95% CI, 1.27 to 13.23]). There was some indication that longer time to treatment was associated with poorer survival for advanced-stage patients, but data quality limited that analysis. CONCLUSION: In the Kathmandu Valley, Nepal, women with a lower education tend to wait longer from BC diagnosis to treatment. Patients with advanced-stage BC had poorer survival, and longer waiting time may be associated with poorer survival for women diagnosed with advanced-stage disease.

Continuous adductor canal block versus continuous femoral nerve block for postoperative pain in patients undergoing knee arthroplasty: An updated meta-analysis of randomized controlled trials.

Continuous adductor canal block (CACB) is almost a pure sensory nerve block and can provide effective analgesia without blocking the motor branch of the femoral nerve. Thus, the objective of this study was to systematically evaluate the efficacy of CACB versus continuous femoral nerve block (CFNB) on analgesia and functional activities in patients undergoing knee arthroplasty. PubMed, Embase and the Cochrane Central Register of Controlled Trials (from inception to 3 October 2023) were searched for randomized controlled trials (RCTs) that compared CACB with CFNB in patients undergoing knee arthroplasty. Registration in the PROSPERO International prospective register of the meta-analysis was completed, prior to initiation of the study (registration number: CRD42022363756). Two independent reviewers selected the studies, extracted data and evaluated risk of bias by quality assessment. Revman 5.4 software was used for meta-analysis and the summary effect measure were calculated by mean differences and 95% confidence intervals. Eleven studies with a total of 748 patients were finally included. Pooled analysis suggested that both CACB and CFNB showed the same degree of pain relief at rest and at motion at 12 h, 24 h and 48 h in patients undergoing knee arthroplasty. Compared with CFNB, CACB preserved the quadriceps muscle strength better (P<0.05) and significantly shortened the discharge readiness time (P<0.05). In addition, there was no significant difference in opioid consumption, knee extension and flexion, timed up and go (TUG) test, or risk of falls between the two groups. Thus, Compared with CFNB, CACB has similar effects on pain relief both at rest and at motion and opioid consumption for patients undergoing knee arthroplasty, while CACB is better than CFNB in preserving quadriceps muscle strength and shortening the discharge readiness time.

Epicardial adipose tissue volume highly correlates with left ventricular diastolic dysfunction in endogenous Cushing's syndrome.

BACKGROUND: Cushing's syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters. METHODS: A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD. RESULTS: A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively. CONCLUSION: CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.

This study explored the potential risk factors of LVDD in endogenous CS by incorporating body composition parameters. EATV was identified as an independent risk factor for LVDD. Targeted therapeutic interventions to reduce excessive cortisol-induced EAT accumulation may be promising to mitigate the risk of LVDD development in patients with CS.

The relationship between serum 1,5-anhydroglucitol and adverse outcomes in acute coronary syndrome with and without chronic kidney disease patients.

Purpose: Individuals with chronic kidney disease (CKD) face an elevated residual risk of cardiovascular events, but the relationship between this residual risk and 1,5-anhydroglucitol (1,5-AG) is uncertain. Our study aimed to examine the effect of 1,5-AG on major adverse cardiovascular events (MACEs) and all-cause mortality in acute coronary syndrome (ACS) individuals. Methods: 1253 ACS participants hospitalized were enrolled at Beijing Hospital between March 2017 and March 2020. All participants were classified into 2 groups based on their eGFR (60 ml/min/1.73 m2). The link between 1,5-AG and adverse outcome was investigated in non-CKD and CKD participants. Results: CKD patients had reduced concentrations of 1,5-AG than those without CKD. Throughout a median follow-up duration of 43 months, 1,5-AG was an autonomous hazard factor for MACEs and all-cause mortality. 1,5-AG<14 µg/ml participants had greater MACEs and all-cause mortality risk than those with 1,5-AG≥14 µg/ml, regardless of renal function. Furthermore, concomitant reduced concentrations of 1,5-AG and CKD portended a dismal prognosis in ACS patients. Conclusions: 1,5-AG was autonomously linked to MACEs and all-cause mortality in ACS participants with both non-CKD and CKD. Co-presence of reduced concentrations of 1,5-AG and CKD may portend adverse clinical outcomes.

Trimethylamine N-oxide predicts cardiovascular events in coronary artery disease patients with diabetes mellitus: a prospective cohort study.

Background: Gut microbiota has significant impact on the cardio-metabolism and inflammation, and is implicated in the pathogenesis and progression of atherosclerosis. However, the long-term prospective association between trimethylamine N-oxide (TMAO) level and major adverse clinical events (MACEs) in patients with coronary artery disease (CAD) with or without diabetes mellitus (DM) habitus remains to be investigated. Methods: This prospective, single-center cohort study enrolled 2090 hospitalized CAD patients confirmed by angiography at Beijing Hospital from 2017-2020. TMAO levels were performed using liquid chromatography-tandem mass spectrometry. The composite outcome of MACEs was identified by clinic visits or interviews annually. Multivariate Cox regression analysis, Kaplan-Meier analysis, and restricted cubic splines were mainly used to explore the relationship between TMAO levels and MACEs based on diabetes mellitus (DM) habitus. Results: During the median follow-up period of 54 (41, 68) months, 266 (12.7%) developed MACEs. Higher TMAO levels, using the tertile cut-off value of 318.28 ng/mL, were significantly found to be positive dose-independent for developing MACEs, especially in patients with DM (HR 1.744, 95%CI 1.084-2.808, p = 0.022). Conclusions: Higher levels of TMAO are significantly associated with long-term MACEs among CAD patients with DM. The combination of TMAO in patients with CAD and DM is beneficial for risk stratification and prognosis.

Color-Tunable CsCdCl3 Perovskite for Low-Temperature Anticounterfeiting and Information Storage Applications.

Low-temperature anticounterfeiting technologies play a crucial role in ensuring the authenticity and integrity of temperature-sensitive products such as vaccines, pharmaceuticals, and food items. In this work, a low-temperature anticounterfeiting route based on the differentiated photoluminescence (PL), PersL, and thermally stimulated luminescence (TSL) behaviors of metal halide perovskite, pure CsCdCl3, and CsCdCl3:10% Te4+ is proposed. The CsCdCl3 host exhibits pronounced color shifts, encompassing PL, PersL, and TSL behaviors, ranging from blue to yellow and orange as the temperature rises from 100 K to room temperature. This color change is attributed to a change in the luminous center (from the D3d octahedron to the C3v octahedron). Conversely, the addition of Te4+ as the luminescence center inhibits the matrix emission, maintains the characteristic orange emission of Te4+, and regulates the trap distribution of the matrix at low temperature and the TL luminescence intensity. This work highlights the significant promise of CsCdCl3:10% Te4+ and CsCdCl3 phosphors as innovative low-temperature anticounterfeiting technologies, especially for cold-chain vaccine safety monitoring.

A predictive model to explore risk factors for severe COVID-19.

With the rapid spread of the novel coronavirus (COVID-19), a sustained global pandemic has emerged. Globally, the cumulative death toll is in the millions. The rising number of COVID-19 infections and deaths has severely impacted the lives of people worldwide, healthcare systems, and economic development. We conducted a retrospective analysis of the characteristics of COVID-19 patients. This analysis includes clinical features upon initial hospital admission, relevant laboratory test results, and imaging findings. We aimed to identify risk factors for severe illness and to construct a predictive model for assessing the risk of severe COVID-19. We collected and analyzed electronic medical records of confirmed COVID-19 patients admitted to the Affiliated Hospital of Jiangsu University (Zhenjiang, China) between December 18, 2022, and February 28, 2023. According to the WHO diagnostic criteria for the novel coronavirus, we divided the patients into two groups: severe and non-severe, and compared their clinical, laboratory, and imaging data. Logistic regression analysis, the least absolute shrinkage and selection operator (LASSO) regression, and receiver operating characteristic (ROC) curve analysis were used to identify the relevant risk factors for severe COVID-19 patients. Patients were divided into a training cohort and a validation cohort. A nomogram model was constructed using the "rms" package in R software. Among the 346 patients, the severe group exhibited significantly higher respiratory rates, breathlessness, altered consciousness, neutrophil-to-lymphocyte ratio (NLR), and lactate dehydrogenase (LDH) levels compared to the non-severe group. Imaging findings indicated that the severe group had a higher proportion of bilateral pulmonary inflammation and ground-glass opacities compared to the non-severe group. NLR and LDH were identified as independent risk factors for severe patients. The diagnostic performance was maximized when NLR, respiratory rate (RR), and LDH were combined. Based on the statistical analysis results, we developed a COVID-19 severity risk prediction model. The total score is calculated by adding up the scores for each of the twelve independent variables. By mapping the total score to the lowest scale, we can estimate the risk of COVID-19 severity. In addition, the calibration plots and DCA analysis showed that the nomogram had better discrimination power for predicting the severity of COVID-19. Our results showed that the development and validation of the predictive nomogram had good predictive value for severe COVID-19.

Brushy C-Decorated BiTe-Based Thermoelectric Film for Efficient Photodetection and Photoimaging.

Current strategies for simultaneously achieving high thermoelectric performance and high light absorption efficiency still suffer from complex steps and high costs. Herein, two kinds of amorphous thermoelectric films of n-type Bi2Te3 and p-type Bi0.5Sb1.5Te3 with high Seebeck coefficients were prepared by pulsed laser deposition (PLD) technology. In addition, C-decorated films with excellent light absorption efficiency at the junction of the thermoelectric legs were prepared by simple drop coating and reactive ion etching (RIE) method. The TE/C-RIE composite device exhibits excellent photodetection performance under the conditions of simulated natural light, monochromatic light, and high-frequency chopping. The maximum responsivity and specific detectivity of the device can reach 153.58 mV W-1 and 6.97 × 106 cm Hz1/2 W-1 (under simulated natural light), respectively. This represents an improvement rate of 85.91% compared to that of the pure TE device. Benefiting from the excellent photodetection efficiency of the device and integration advantage of PLD technology, the composite structure can be expanded into integrated photoimaging devices. The accurate identification of patterned light sources with letters (T, J, and U) and digitals (0-9) was successfully realized by associating the response electrical signals of each electrode with the position coordinates. This work provides valuable guidance for the design and fabrication of wide-spectrum photodetectors and complex optical imaging devices.

Impact of COVID-19 pandemic on routine childhood vaccinations.

Routine pediatric vaccination is one of the most effective public health inter-ventions for the control of a number of fatal diseases. However, during the coronavirus disease 2019 pandemic, routine pediatric vaccination rates were severely affected by disruptions of health services and vaccine confidence issues. Governments and the United Nations have taken measures to re-establish routine pediatric vaccination, while additional efforts are needed to catch up and develop plans to ensure routine vaccination services for the future pandemics.

Psoralen attenuates cigarette smoke extract-induced inflammation by modulating CD8+ T lymphocyte recruitment and chemokines via the JAK2/STAT1 signaling pathway.

Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Psoralen (PSO) is the main pharmacological component identified from Bu-Shen-Fang-Chuan formula which has been traditionally used in treatment of COPD, yet its efficacy in COPD inflammation were unreported. In this study, we aimed to elucidate the anti-inflammatory potential of PSO in COPD and unravel the underlying mechanisms, focusing on T lymphocyte recruitment and the modulation of chemokines, namely monokine induced by interferon-gamma (CXCL9), interferon inducible protein 10 (CXCL10), and interferon inducible T-Cell alpha chemoattractant (CXCL11). In vitro, RAW264.7 was stimulated by interferon (IFN)-γ + cigarette smoke extract (CSE) and were treated with PSO (2.5, 5, 10 µM), then the levels of chemokines and the activation of Janus kinase (JAK)/Signal transducer and activator of transcription 1 (STAT1) pathway were analyzed by real time PCR and western blot. In vivo, a murine model was established by intraperitoneal injection of CSE on day 1, 8, 15, and 22, then treated with PSO (10 mg/kg). Our experiments in vitro illustrated that PSO reduced the levels of CXCL9, CXCL10, and CXCL11, and decreased the protein phosphorylation levels of JAK2 and STAT1. Additionally, PSO effectively improved inflammatory infiltration and decreased the proportion of CD8+ T cells in CSE-exposed mice. Furthermore, PSO reduced the levels of CXCL9, CXCL10, and CXCL11 in bronchoalveolar lavage fluid (BALF) and lung tissue, and decreased the protein phosphorylation levels of JAK2 and STAT1. In conclusion, our results revealed the therapeutic potential of PSO for COPD inflammation, possibly mediated through the regulation of CD8+ T cell recruitment and chemokines via the JAK2/STAT1 signaling pathway.

Crystal Field-Engineered Cr3+-Doped Gd3(MgxGa5-2xGex)O12 Phosphors for Near-Infrared LEDs and X-ray Imaging Applications.

Inorganic materials doped with chromium (Cr) ions generate remarkable and adjustable broadband near-infrared (NIR) light, offering promising applications in the fields of imaging and night vision technology. However, achieving high efficiency and thermal stability in these broadband NIR phosphors poses a significant challenge for their practical application. Here, we employ crystal field engineering to modulate the NIR characteristics of Cr3+-doped Gd3Ga5O12 (GGG). The Gd3MgxGa5-2xGexO12 (GMGG):7.5% Cr3+ (x = 0, 0.05, 0.15, 0.20, and 0.40) phosphors with NIR emission are developed through the cosubstitution of Mg2+ and Ge4+ for Ga3+ sites. This cosubstitution strategy also effectively reduces the crystal field strength around Cr3+ ions, which results in a significant enhancement of the photoluminescence (PL) full width at half-maximum (fwhm) from 97 to 165 nm, alongside a red shift in the PL peak and an enhancement of the PL intensity up to 2.3 times. Notably, the thermal stability of the PL behaviors is also improved. The developed phosphors demonstrate significant potential in biological tissue penetration and night vision, as well as an exceptional scintillation performance for NIR scintillator imaging. This research paves a new perspective on the development of high-performance NIR technology in light-emitting diodes (LEDs) and X-ray imaging applications.

A black phosphorus nanosheet-based RNA delivery system for prostate cancer therapy by increasing the expression level of tumor suppressor gene PTEN via CeRNA mechanism.

BACKGROUND: Prostate cancer (PCa) has a high incidence in men worldwide, and almost all PCa patients progress to the androgen-independent stage which lacks effective treatment measures. PTENP1, a long non-coding RNA, has been shown to suppress tumor growth through the rescuing of PTEN expression via a competitive endogenous RNA (ceRNA) mechanism. However, PTENP1 was limited to be applied in the treatment of PCa for the reason of rapid enzymatic degradation, poor intracellular uptake, and excessively long base sequence to be synthesized. Considering the unique advantages of artificial nanomaterials in drug loading and transport, black phosphorus (BP) nanosheet was employed as a gene-drug carrier in this study. RESULTS: The sequence of PTENP1 was adopted as a template which was randomly divided into four segments with a length of about 1000 nucleotide bases to synthesize four different RNA fragments as gene drugs, and loaded onto polyethyleneimine (PEI)-modified BP nanosheets to construct BP-PEI@RNA delivery platforms. The RNAs could be effectively delivered into PC3 cells by BP-PEI nanosheets and elevating PTEN expression by competitive binding microRNAs (miRNAs) which target PTEN mRNA, ultimately exerting anti-tumor effects. CONCLUSIONS: Therefore, this study demonstrated that BP-PEI@RNAs is a promising gene therapeutic platform for PCa treatment.

Modular Fabrication of Microfluidic Graphene FET for Nucleic Acids Biosensing.

Graphene field-effect transistors (GFETs) are widely used in biosensing due to their excellent properties in biomolecular signal amplification, exhibiting great potential for high-sensitivity and point-of-care testing in clinical diagnosis. However, difficulties in complicated fabrication steps are the main limitations for the further studies and applications of GFETs. In this study, a modular fabrication technique is introduced to construct microfluidic GFET biosensors within 3 independent steps. The low-melting metal electrodes and intricate flow channels are incorporated to maintain the structural integrity of graphene and facilitate subsequent sensing operations. The as-fabricated GFET biosensor demonstrates excellent long-term stability, and performs effectively in various ion environments. It also exhibits high sensitivity and selectivity for detecting single-stranded nucleic acids at a 10 fm concentration. Furthermore, when combined with the CRISPR/Cas12a system, it facilitates amplification-free and rapid detection of nucleic acids at a concentration of 1 fm. Thus, it is believed that this modular-fabricated microfluidic GFET may shed light on further development of FET-based biosensors in various applications.

Effect of Bioactive Black Phosphorus Nanomaterials on Cancer-Associated Fibroblast Heterogeneity in Pancreatic Cancer.

Tumor-stromal interactions and stromal heterogeneity in the tumor microenvironment are critical factors that influence the progression, metastasis, and chemoresistance of pancreatic ductal adenocarcinoma (PDAC). Here, we used spatial transcriptome technology to profile the gene expression landscape of primary PDAC and liver metastatic PDAC after bioactive black phosphorus nanomaterial (bioactive BP) treatment using a murine model of PDAC (LSL-KrasG12D/+; LSL-Trp53R172H/+; and Pdx-1-Cre mice). Bioinformatic and biochemical analyses showed that bioactive BP contributes to the tumor-stromal interplay by suppressing cancer-associated fibroblast (CAF) activation. Our results showed that bioactive BP contributes to CAF heterogeneity by decreasing the amount of inflammatory CAFs and myofibroblastic CAFs, two CAF subpopulations. Our study demonstrates the influence of bioactive BP on tumor-stromal interactions and CAF heterogeneity and suggests bioactive BP as a potential PDAC treatment.

Case report: A patient with brachio-cervical inflammatory myopathy was misdiagnosed as flail arm syndrome.

Brachio-cervical inflammatory myopathy (BCIM) is a rare inflammatory myopathy characterized by dysphagia, bilateral upper limb atrophy, limb-girdle muscle weakness, and myositis-specific antibody (MSA) negativity. BCIM has a low incidence and is commonly associated with autoimmune diseases. We present a case report of a 55-year-old man with progressive upper limb weakness and atrophy, diagnosed with flail arm syndrome (FAS). The initial electromyography revealed extensive spontaneous muscle activity and increased duration of motor unit potentials (MUPs). During follow-up, evidence of myogenic damage was observed, as indicated by a decreased duration of MUPs in the right biceps muscle. Laboratory and genetic testing ruled out hereditary or acquired diseases. Negative serological antibodies for myasthenia gravis. Hereditary or acquired diseases were ruled out through laboratory and genetic testing. Whole-body muscle magnetic resonance imaging (MRI) showed extensive edema and fat replacement in the bilateral upper limbs, scapular, and central axis muscles, while the lower extremities were relatively mildly affected. Muscle biopsy revealed numerous foci of inflammatory cells distributed throughout the muscle bundle, with predominant CD20, CD138, and CD68 expression, accompanied by a light infiltration of CD3 and CD4 expression. The muscle weakness improved with the combination of oral prednisone (initially 60 mg/day, tapered) and methotrexate (5 mg/week) treatment.

Impact of cancer diagnosis on life expectancy by area-level socioeconomic groups in New South Wales, Australia: a population-based study.

OBJECTIVE: Improvement in cancer survival over recent decades has not been accompanied by a narrowing of socioeconomic disparities. This study aimed to quantify the loss of life expectancy (LOLE) resulting from a cancer diagnosis and examine disparities in LOLE based on area-level socioeconomic status (SES). METHODS: Data were collected for all people between 50 and 89 years of age who were diagnosed with cancer, registered in the NSW Cancer Registry between 2001 and 2019, and underwent mortality follow-up evaluations until December 2020. Flexible parametric survival models were fitted to estimate the LOLE by gender and area-level SES for 12 common cancers. RESULTS: Of 422,680 people with cancer, 24% and 18% lived in the most and least disadvantaged areas, respectively. Patients from the most disadvantaged areas had a significantly greater average LOLE than patients from the least disadvantaged areas for cancers with high survival rates, including prostate [2.9 years (95% CI: 2.5-3.2 years) vs. 1.6 years (95% CI: 1.3-1.9 years)] and breast cancer [1.6 years (95% CI: 1.4-1.8 years) vs. 1.2 years (95% CI: 1.0-1.4 years)]. The highest average LOLE occurred in males residing in the most disadvantaged areas with pancreatic [16.5 years (95% CI: 16.1-16.8 years) vs. 16.2 years (95% CI: 15.7-16.7 years)] and liver cancer [15.5 years (95% CI: 15.0-16.0 years) vs. 14.7 years (95% CI: 14.0-15.5 years)]. Females residing in the least disadvantaged areas with thyroid cancer [0.9 years (95% CI: 0.4-1.4 years) vs. 0.6 years (95% CI: 0.2-1.0 years)] or melanoma [0.9 years (95% CI: 0.8-1.1 years) vs. 0.7 years (95% CI: 0.5-0.8 years)] had the lowest average LOLE. CONCLUSIONS: Patients from the most disadvantaged areas had the highest LOLE with SES-based differences greatest for patients diagnosed with cancer at an early stage or cancers with higher survival rates, suggesting the need to prioritise early detection and reduce treatment-related barriers and survivorship challenges to improve life expectancy.

Improved Patient Adherence to Family-Based Helicobacter pylori Infection Control and Management Strategy in Central China and Its Influencing Factors.

BACKGROUND: Patient adherence status to the newly introduced family-based Helicobacter pylori (H. pylori) infection control and management strategy remains unclear, so are its influencing factors. We aim to investigate family members' adherence and its influencing factors during the family-based H. pylori infection management practice for related disease prevention. MATERIALS AND METHODS: Based on our previously family-based H. pylori survey in 2021, 282 families including 772 individuals were followed up 2 years after the initial survey to compare if the investigation and education might improve family member's adherence. The participant's adherence to H. pylori infection awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were followed up, and their influencing factors were also analyzed. RESULTS: The overall participant's adherence to recommendations on H. pylori awareness, retest, treatment, publicity, gastroscopy, and hygiene habits were 77% (187/243), 67.3% (138/205), 60.1% (211/351), 46.5% (107/230), 45.6% (159/349), and 39.1% (213/545), respectively; and all showed improvements compared with their prior survey stages. The top reasons for rejection to treatment, retest, and gastroscopy were forgetting or unaware of H. pylori infection (30.3%), busy (32.8%), and asymptomatic (67.9%), respectively. Independent risk factor for low adherence to treatment was occupation (e.g., staff: OR 4.49, 95% CI 1.34-15.10). Independent favorable factors for treatment adherence were individuals at the ages of 18-44 years (OR 0.19, 95% CI 0.04-0.89) and had a large family size (e.g., four family members: OR 0.15, 95% CI 0.06-0.41); for retest adherence, it was individuals at the ages of 60-69 years (OR 0.23, 95% CI 0.06-0.97); for gastroscopy adherence, it was individuals at the age of 60-69 years (OR 0.46, 95% CI 0.28-0.75), and with gastrointestinal symptoms (OR 0.57, 95% CI 0.36-0.90). CONCLUSIONS: Family-based H. pylori management increases individual adherence to treatment, retest, and awareness, and there are also improved adherence to gastroscopy, publicity, and personal hygiene recommendations; further efforts are required to enhance the individual adherence rate for related disease prevention.

Current insights into human pathogenic phenuiviruses and the host immune system.

Phenuiviruses are a class of segmented negative-sense single-stranded RNA viruses, typically consisting of three RNA segments that encode four distinct proteins. The emergence of pathogenic phenuivirus strains, such as Rift Valley fever phlebovirus (RVFV) in sub-Saharan Africa, Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in East and Southeast Asia, and Heartland Virus (HRTV) in the United States has presented considerable challenges to global public health in recent years. The innate immune system plays a crucial role as the initial defense mechanism of the host against invading pathogens. In addition to continued research aimed at elucidating the epidemiological characteristics of phenuivirus, significant advancements have been made in investigating its viral virulence factors (glycoprotein, non-structural protein, and nucleoprotein) and potential host-pathogen interactions. Specifically, efforts have focused on understanding mechanisms of viral immune evasion, viral assembly and egress, and host immune networks involving immune cells, programmed cell death, inflammation, nucleic acid receptors, etc. Furthermore, a plethora of technological advancements, including metagenomics, metabolomics, single-cell transcriptomics, proteomics, gene editing, monoclonal antibodies, and vaccines, have been utilized to further our understanding of phenuivirus pathogenesis and host immune responses. Hence, this review aims to provide a comprehensive overview of the current understanding of the mechanisms of host recognition, viral immune evasion, and potential therapeutic approaches during human pathogenic phenuivirus infections focusing particularly on RVFV and SFTSV.

S1P/S1PR1 signaling is involved in the development of nociceptive pain.

Background: Pain is a complex perception involving unpleasant somatosensory and emotional experiences. However, the underlying mechanisms that mediate its different components remain unclear. Sphingosine-1-phosphate (S1P), a metabolite of sphingomyelin and a potent lipid mediator, initiates signaling via G protein-coupled receptors (S1PRs) on cell surfaces. It serves as a second messenger in cellular processes such as proliferation and apoptosis. Nevertheless, the neuropharmacology of sphingolipid signaling in pain conditions within the central nervous system remains largely unexplored and controversial. Methods: Chronic nociceptive pain models were induced in vivo by intraplantar injection of 20 µL complete Freund's adjuvant (CFA) into the left hind paws. We assessed S1P and S1PR1 expression in the spinal cords of CFA model mice. Functional antagonists of S1PR1 or S1PR1-specific siRNA were administered daily following CFA model establishment. Paw withdrawal response frequency (PWF) and paw withdrawal latency (PWL) were measured to evaluate mechanical allodynia and thermal hyperalgesia, respectively. RT-PCR assessed interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α levels. Western blotting and immunofluorescence were used to analyze glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule (Iba1), STAT3, ERK, and p38 MAPK protein expression. Results: In the chronic nociceptive pain model induced by CFA, S1P and S1PR1 expression levels were significantly elevated, leading to activation of spinal cord glial cells. S1PR1 activation also promoted MMP2-mediated cleavage of mature IL-1ß. Additionally, S1PR1 activation upregulated phosphorylation of STAT3, ERK, and p38 MAPK in glial cells, profoundly impacting downstream signaling pathways and contributing to chronic nociceptive pain. Conclusion: The S1P/S1PR1 axis plays a pivotal role in the cellular and molecular mechanisms underlying nociceptive pain. This signaling pathway modulates glial cell activation and the expression of pain-related genes (STAT3, ERK, p38 MAPK) and inflammatory factors in the spinal dorsal horn. These findings underscore the potential of targeting the S1P system for developing novel analgesic therapies.

Multiple myeloma survival in New South Wales, Australia, by treatment era to 2020.

OBJECTIVE: Australia has relatively high multiple myeloma (MM) incidence and mortality rates. Advancements in MM treatment over recent decades have driven improvements in MM survival in high-income countries; however, reporting in Australia is limited. We investigated temporal trends in population-wide MM survival across 3 periods of treatment advancements in New South Wales (NSW), Australia. METHODS: Individuals with an MM diagnosis in the NSW Cancer Registry between 1985 and 2015 with vital follow-up to 2020, were categorized into 3 previously defined treatment eras according to their diagnosis date (1985-1995, chemotherapy only; 1996-2007, autologous stem cell transplantation; and 2008-2015, novel agents including proteasome inhibitors and immunomodulatory drugs). Both relative survival and cause-specific survival according to Fine and Gray's competing risks cumulative incidence function were calculated by treatment era and age at diagnosis. RESULTS: Overall, 11,591 individuals were included in the study, with a median age of 70 years at diagnosis. Five-year relative survival improved over the 36-year (1985-2020) study period (31.0% in 1985-1995; 41.9% in 1996-2007; and 56.1% in 2008-2015). For individuals diagnosed before 70 years of age, the 5-year relative survival nearly doubled, from 36.5% in 1985-1995 to 68.5% in 2008-2015. Improvements for those > 70 years of age were less pronounced between 1985-1995 and 1996-2007; however, significant improvements were observed for those diagnosed in 2008-2015. Similar overall and age-specific patterns were observed for cause-specific survival. After adjustment for gender and age at diagnosis, treatment era was strongly associated with both relative and cause-specific survival (P < 0.0001). CONCLUSIONS: Survival of individuals with MM is improving in Australia with treatment advances. However, older age groups continue to experience poor survival outcomes with only modest improvements over time. Given the increasing prevalence of MM in Australia, the effects of MM treatment on quality of life, particularly in older age, warrant further attention.