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A good old gateway theory that electronic-cigarettes (e-cigarettes) are widely recognized as safer tobacco substitutes. In actuality, demographics also show that vaping cannibalizes smoking, the best explanation of the data is the "common liability". However, the utilization of e-cigarette products remains a controversial topic at present. Currently, there has been a widespread and substantial growth in e-cigarette use worldwide owing to their endless new flavors and customizable characteristics. Furthermore, e-cigarette has grown widespread among smokers as well as non-smokers, including adolescents and young adults. And some studies have shown that e-cigarette users are at greater risk to start using combustible cigarettes while e-cigarettes use was also observed the potential benefits to people who want to quit smoking or not. Although it is true that e-cigarettes generally contain fewer toxic substances than combustible cigarettes, this does not mean that the chemical composition in e-cigarettes aerosols poses absolutely no risks. While concerns about toxic substances in e-cigarettes and their widespread use in the population are reasonable, it is also crucial to consider that e-cigarettes have been associated with the potential for promoting smoking cessation and the clinically relevant improvements in users with smoking-related pathologies. Meanwhile, there is still short of understanding of the health impacts associated with e-cigarette use. Therefore, in this review, we discussed the health impacts of e-cigarette exposure on oral, nasal, pulmonary, cardiovascular systems and brain. We aspire for this review to change people's previous perceptions of e-cigarettes and provide them with a more balanced perspective. Additionally, we suggest appropriate adjustments on regulation and policy for e-cigarette to gain greater public health benefits. [ABSTRACT FROM AUTHOR]

To examine whether facility-reported staff shortages and total staff levels were independently associated with changes in nursing home (NH) outcomes in 2020. Longitudinal cohort study. A total of 8466 NHs with staffing and outcome data. This study used NH COVID-19 Public File (2020), Nursing Home Compare (2019-2020), and Payroll-Based Journal data (2019-2020). Outcome measures included the percentage of long-stay residents in a facility with declines in activities in daily living (ADLs), decreases in mobility, weight loss, and pressure ulcers in 2020 Q2, 2020 Q3, and 2020 Q4. Independent variables were whether NHs reported any shortage of aides or licensed nurses and total staff hours per resident day (HPRD). Separate 2-level (NH, state) Hierarchical Generalized Linear Mixed models examined the association of facility-reported shortages and staff hours with key NH resident outcomes, controlling for NH characteristics and COVID-19 infections. The weekly percentage of NHs reporting any staff shortage averaged 20%. Total staff HPRD increased slightly from 3.7 in 2019 to 3.8 in 2020. Health outcomes were stable during 2019 and 2020 Q1 but worsened substantially starting in 2020 Q2. For example, the percentage of residents with mobility loss increased from 16.2% in 2020 Q1 to 27.9% in 2020 Q4. Facility-reported staff shortages were associated with an increase in the proportion of residents with an ADL decline (0.54 percentage points), mobility loss (0.80 percentage points), weight loss (0.22 percentage points), and pressure ulcers (0.22 percentage points) (all P <.01). Total staff HPRD was not associated with changes in any outcomes (all P >.05). NHs reported worsened health outcomes among long-stay residents in 2020, with worse outcomes found among facilities that reported staff shortages but not among those with lower total staff levels. Facility-reported shortages provide important quality information during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Exosomes are a class of extracellular vesicles released by bacteria and contain diverse biomolecules. In this study, we isolated exosomes from Vibrio harveyi and Vibrio anguillarum , which are both serious pathogens in mariculture, using a supercentrifugation method, and the proteins in the exosomes of these two vibrios were analyzed by LC-MS/MS proteomics. Exosome proteins released by V. harveyi and V. anguillarum were different; they not only contained virulence factors (such as lipase and phospholipase in V. harveyi , metalloprotease and hemolysin in V. anguillarum), but also participated in the important life activities of bacteria (such as fatty acid biosynthesis, biosynthesis of antibiotics, carbon metabolism). Subsequently, to verify whether the exosomes participated in bacterial toxicity, after Ruditapes philippinarum was challenged with V. harveyi and V. anguillarum , the corresponding genes of virulence factors from exosomes screened by proteomics were tested by quantitative real-time PCR. All the genes detected were upregulated which suggested that exosomes were involved in vibrio toxicity. The results could provide an effective proteome database for decoding the pathogenic mechanism of vibrios from the exosome perspective. • Exosomes proteins released by V. harveyi and V. anguillarum contained virulence factors. • Exosomes proteins released by V. harveyi and V. anguillarum participated in the complex biological processes of bacteria. • Corresponding virulence factors of exosomes in V. harveyi and V. anguillarum involved in bacteria toxicity. [ABSTRACT FROM AUTHOR]

• A nontraditional NaIO 4 oxidized sugar (NOXIN) was synthesized from inositol. • NOXIN exhibited better crosslinking powder and structural stability. • A nonmonotonic dose–effect of NOXIN in stabilizing RSC was observed. • NOXIN has a wide substrate scope and is potentially applicable in other food systems. Rehydrated sea cucumber (RSC) is a popular seafood in northeast Asia with high deep-processing potential. Yet the development of value-added RSC product is limited by non-enzymatic decrosslinking of RSC collagen hydrogel system, which could potentially be solved by crosslinking enhancement. In this work, NaIO 4 oxidized inositol (NOXIN), a novel crosslinker, was synthesized and its capacity in RSC stabilization was evaluated with texture profile analysis, free amino group content, total soluble protein, water activity, water withholding capacity and scanning electron microscope (SEM). The results show that NOXIN could stabilize RSC in a dose dependent manner by crosslinking the amino groups on collagen, thus enhances the mechanical strength and water holding capacity, retains water activity, and suppresses protein degradation of the hydrogel system, although overdosing compromises the stabilizing effect. The results of this study have not only validated the capacity of NOXIN as protein crosslinker, but also provided reference to the development of new crosslinkers. [ABSTRACT FROM AUTHOR]

• The VSA and the SSA with PS are described under the same framework of PSAs. • A generalized monopulse algorithm is proposed to jointly estimate DOA and polarization parameters. • The closed-form expressions for parameter estimation error variances are derived. • The polarization estimation variance is proved to decrease monotonically with the PS factor. In this paper, the vector sensor array (VSA) and the scalar sensor array (SSA) with polarization sensitivity (PS) are placed under the same framework of polarization sensitive arrays (PSAs), whose direction-dependent PS factor is larger than zero. This commonality of their PS factors enables both VSA and SSA to perform polarization estimation effectively. Based on this new PSA model, a generalized monopulse algorithm is proposed to jointly estimate direction-of-arrival (DOA) and polarization parameters, by expanding the existing monopulse angle estimation in spatial domain to both spatial and polarization domains. Both the DOA and polarization parameters can be effectively and efficiently estimated by comparing the outputs of the sum and spatial/polarized difference beams with only one snapshot. Then, closed-form expressions for joint DOA and polarization estimation error variances are derived and the polarization estimation variance is proved to decrease monotonically with the PS factor. Simulations are carried out on an X-band 5 × 5 planar array composed of microstrip patch antennas to demonstrate the effectiveness of the proposed algorithm. [ABSTRACT FROM AUTHOR]

As the new display technology, Micro-LEDs are of the advantages of low power consumption, high brightness, high resolution and fast response time. However, the strong surface non-radiative recombination significantly reduces their efficiency. Some techniques such as epitaxial growth or wet sulfide have been introduced to inhibit the surface recombination, but these expensive or unstable methods ignore the operability of industrial production. Herein, we use an ion implantation method to modify the high-density surface defects on the sidewall, thereby improve the luminous efficiency effectively by inhibiting carrier surface non-radiative recombination. The photoelectric performances of GaN-based Micro-LEDs after N ion implantation were studied. The characterization results indicated that the photoluminescence intensity of Micro-LEDs was increased by 7 times after passivation, which was attributed to the significant elimination of sidewall damage. In addition, the removal of the surface dangling bonds and oxidized nitrides (Ga–N or Ga-OH bonds) after the passivation process were further proved by Auger electron spectroscopy characterization. As a result of the N ion implantation, the external quantum efficiency of packaged Micro-LEDs chip increased about 33%. Therefore, this manuscript will provide a new direction for improving the photoelectric performance of Micro-LEDs. • Ion implantation was used to solve the efficiency decline in Micro-LEDs. • Non-radiative recombination was significantly reduced after N ion implantation. • The injected N ions effectively reduce the existence of defect states. • The EQE of Micro-LEDs increased by 33% at the current density of 10 A/cm2. [ABSTRACT FROM AUTHOR]

The micro lighting-emitting diode (Micro-LED) array devices have attracted attention due to increasing demand in augmented reality (AR), virtual reality (VR), LIFI light source, and other micro-display applications. However, with the decrease of micro-LED diameter, the performance of micro-LED is severely limited due to the size effect. In the work, the AlGaInP based red micro-LED with diameter ranging from 2 to 16 μm was prepared to study the size effect of micro-LED array, the array with larger micro-LED diameter show higher external quantum efficiency (EQE), meanwhile, the carrier lifetime decrease with the decreasing of the diameter, which can be explained by more surface states in the micro-LED with smaller diameter. The enhancement of EQE by 2 times has been achieved after surface passivation in (NH 4) 2 S x solution. • Micro-LED diameter ranging from 2 to 16 μm was fabricated, and the influence of size effect on the photoelectric performance was studied. • A fast and low-cost surface passivation method was used to successfully reduce the surface state density, and increase EQE of the Micro-LED array by 2 times. • The cause of size effect is clearly explained and the device performance is successfully optimized through surface passivation, which provides valuable guidance for the future commercialization of micro-LED. [ABSTRACT FROM AUTHOR]

Background and Objective: To explore the association between protein quantitative trait loci (pQTL-SNPs) and the risk of LUAD., Methods: "Blood +" high depth blood proteomics analysis was performed on plasma from female LUAD patients and female healthy controls, and combined with proteomics data from tumors and adjacent non-tumor tissues of female LUAD patients to screen proteins uniformly expressed in plasma and tissues. pQTL-SNPs were then screened through multiple databases and subjected to multilevel screening. The associations between selected pQTL-SNPs and LUAD risk were evaluated by Female Lung Cancer Consortium in Asia GWAS (FLCCA GWAS). Enzyme linked immunosorbent assay (ELISA) is used to determine the levels of candidate protein., Results: A total of 7 pQTL-SNPs were significantly associated with altered LUAD risk (p < 0.05). Meanwhile, the expression of their corresponding target proteins were all decreased in both plasma and tumor tissues of LUAD cases, which may play a role of tumor suppressor proteins. After mutation of 3 pQTL-SNPs (rs7683000, rs73224660, and rs2776937), the expression of corresponding target proteins BST1 and NRP1 decreased, and as potential tumor suppressor proteins, which may promote tumorigenesis and further increasing the risk of developing LUAD (OR >1, p < 0.05); while after mutation the other pQTL-SNP rs62069916, the corresponding target protein APOH expression was increased, while as a potential tumor suppressor protein, which may inhibit tumorigenesis and further reduced the risk of developing LUAD (OR <1, p < 0.05). In addition, the expression of NRP1 and APOH were significant decreased in LUAD cell lines and validated in plasma of LUAD patients., Conclusion: A total of 4 pQTL-SNPs (rs7683000, rs73224660, rs2776937, and rs62069916) may associate with altered LUAD risk by regulating the expression of target proteins (BST1, NRP1, and APOH) after mutation., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Chronic recurrent itch and skin inflammation are prominent features of atopic dermatitis (AD), which is closely related to the immune response driven by T-helper type 2 (Th2) cells. The expression of interleukin 31 (IL-31) is positively correlated with the severity of dermatitis. Anti-IL-31 receptor α (IL-31RA) targeted drugs have been used to treat AD, however, they are expensive and have side effects. Fraxinellone (FRA) is one of the main limonoid components in the dried root bark of Dictamnus dasycarpus Turcz.; however, its anti-inflammatory and antipruritic effects on atopic dermatitis (AD) have not been previously reported. In this study, we investigated the anti-dermatitis effect of FRA and its potential mechanism of action using a 2,4-dinitrofluorobenzene (DNFB)-induced AD-like mouse model and lipopolysaccharide (LPS)-stimulated HaCaT cells. FRA significantly inhibited chronic pruritus, epidermal thickening, and inflammatory infiltration in AD mice. FRA not only inhibited the levels of IL-31 in the serum and lesioned skin of AD mice but also significantly downregulated the mRNA expression and protein levels of IL-31, IL-31RA, transient receptor potential (TRP) V1, and TRPA1 in the lesioned skin and dorsal root ganglion (DRG) of AD mice. In LPS-stimulated HaCaT cells, FRA inhibited the production of iNOS and COX2, as well as the protein levels of IL-31, IL-31RA, TRPV1 and TRPA1, showing significant anti-inflammatory effects. In summary, our findings suggest that FRA exerts antipruritic and anti-inflammatory effects in AD by regulating the IL-31 pathway, and may hold promise for the clinical treatment of AD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Alternative polyadenylation (APA) plays a crucial role in cancer biology. Here, we used data from the 3'aQTL-atlas, GTEx, and the China Nanjing Lung Cancer GWAS database to explore the association between apaQTL/eQTL-SNPs and the risk of lung adenocarcinoma (LUAD). The variant T allele of rs277646 in NIT2 is associated with an increased risk of LUAD (OR = 1.12, P = 0.015), lower PDUI values, and higher NIT2 expression. The 3'RACE experiment showed multiple poly (A) sites in NIT2, with the rs277646-T allele causing preferential use of the proximal poly (A) site, resulting in a shorter 3'UTR transcript. This leads to the loss of the hsa-miR-650 binding site, thereby affecting LUAD malignant phenotypes by regulating the expression level of NIT2. Our findings may provide new insights into understanding and exploring APA events in LUAD carcinogenesis., (© 2024. The Author(s).)

When nursing homes experience a shortage in directly employed nursing staff, they may rely on temporary workers from staffing agencies to fill this gap. This article examines trends in the use of staffing agencies among nursing homes during the prepandemic and COVID-19 pandemic era (2018-22). In 2018, 23 percent of nursing homes used agency nursing staff, accounting for about 3 percent of all direct care nursing hours worked. When used, agency staff were commonly present for ninety or fewer days in a year. By 2022, almost half of all nursing homes used agency staff, accounting for 11 percent of all direct care nursing staff hours. Agency staff were increasingly used to address chronic staffing shortages, with 13.8 percent of nursing homes having agency staff present every day. Agency staff were 50-60 percent more expensive per hour than directly employed nursing staff, and nursing homes that used agency staff often had lower five-star ratings. Policy makers need to consider postpandemic changes to the nursing home workforce as part of nursing home reform, as increased reliance on agency staff may reduce the financial resources available to increase nursing staff levels and improve the quality of care.

Aim: This study aimed to determine the psychosocial markers associated with pre-hospital delay among patients with diabetic foot (DF)., Design: This study has a cross-sectional design., Methods: The participants completed a questionnaire including pre-hospital time, demographic characteristics, Social Support Rate Scale, Brief Illness Perception Questionnaire and Type D Personality Scale-14. Bivariate and multivariate analyses were conducted to explore independent associations with pre-hospital delay., Results: Only 1.8% (3/164) of participants arrived at the hospital for medical care in 24 h of symptom onset. Patients with low utilization of social support (p = 0.029), low negative illness perceptions (p = 0.014) and high levels of negative affectivity (p = 0.009) are likely to arrive late at the clinic. Medical staff should pay attention to identifying diabetic patients' Type D personalities and take actions to improve their social support as well as illness perception, so as to reduce the occurrence of hospital delay., Implications for the Profession And/or Patient Care: Psychosocial factors play a vital role in the delay in seeking medical treatment for patients with DF. Medical staff need to improve patients' illness perception as well as self-management ability through health education. Importantly, key family members provide an emotional and psychological support system for diabetic patients. Therefore, nurses need to work with family members together to give information and psychological support during family visits. Additionally, building and maintaining trust with patients is crucial to encouraging individuals to express their concerns and worries. In this case, nurses may identify patients' negative emotions and conduct timely intervention, so as to achieve favourable outcomes., Patient or Public Contribution: This study used a convenience sample of 164 participants with DF recruited from the wound clinic of Northern Jiangsu People's Hospital and Yangzhou Hospital of TCM in China., (© 2024 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Purpose: The aim of this study was to identify the most meaningful diagnostic indicator for distinguishing blanchable erythema (BE) and stage 1 pressure injury (early PI) in an in vivo (rat) model., Design: A prospective case-control design was used to complete a horizontal and vertical comparison of detection indicators during the process of fading of BE or the deterioration of early PI into ulcer in rat models., Materials and Setting: The sample comprised 5 hairless rats with 20 injuries, of which 10 were BE and the other 10 were early PI. Data were collected at Nagano College of Nursing in 2020 in Nagano, Japan., Methods: The BE and PI rat models were established by subjecting the dorsal skin of a hairless rat to compression between 2 neodymium magnets for 45 minutes and 3.45 hours, respectively. The affected skin was observed based on the following: (1) photography, (2) hardness, (3) temperature, (4) moisture, and (5) spectrophotometric (a* value and ultraviolet [UV] reflectance) measurements. All measurements of BE were performed at the beginning to 60 minutes after decompression, and those for early PI were performed until 48 hours after decompression., Results: Multiple BE factors, such as the degree of erythema (macroscopy and a* value), hardness, temperature, and moisture, were found to have unstable fluctuations. Only UV reflectance gradually decreased from 6 hours and decreased significantly at 48 hours after decompression (P = .001 vs 1 hour). In contrast to early PI, erythema in BE obviously faded within 10 minutes., Conclusions: Study findings indicate that a continuous decrease in UV reflectance can reflect the worsening of hemorrhage in early (stage 1) PI. In contrast, other indicators including photography, skin hardness, temperature, and moisture fluctuated and did not prove predictive for PI progression. The obvious fading of erythema in BE a short time after decompression can be used for clinical observations., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Wound, Ostomy and Continence Nurses Society.)

In 2022, COVID-19 continued to spread across the globe, and to stop the spread of the virus and protect people's health, universities across China continued to remain in a lockdown state. Loneliness is an important topic among college students, and the coronavirus pandemic has exacerbated loneliness. This prolonged school lockdown was unprecedented and it caused severe social isolation and emotional loneliness for students. Few people know how nursing students experience loneliness and find a way through their experience. This qualitative phenomenological study was conducted to reveal the lived experiences of nursing students who indicated COVID-19 lockdown-related loneliness in a previous quantitative survey. We performed 20 semi-structured interviews with nursing students aged 19-23 yrs during their lockdown (April 2022 to June 2022). Our research applied Colaizzi's seven-step data analysis processes to reveal shared patterns in terms of how nursing students experienced lockdown and found the following four themes: emotional challenges associated with loneliness; causes of loneliness; positive and negative motivation to learn; and accepting solitude and reconstructing real life.

Introduction: An effective salvage regimen for the reinduction of remission is lacking for refractory or relapsed primary central nervous system lymphoma (r/r PCNSL). This study aimed to evaluate the efficacy and safety of cytarabine plus temozolomide in treating r/r PCNSL and to explore the associated prognostic factors., Methods: A single-center retrospective cohort study was conducted to assess the efficacy and safety of cytarabine and temozolomide (AT) in r/r PCNSL patients. KIR and HLA genotyping was performed on peripheral blood samples., Results: Thirty PCNSL patients receiving an AT regimen (cytarabine 3 g/m 2 for 2 days combined with temozolomide 150 mg/m 2 for 5 days) in our institution were analyzed. The median age was 65 years (range 25-79 years). A total of 43.4% of patients (13/30) achieved an overall response within a median follow-up of 16 months (95% confidence interval [CI]: 11-23 months). The median PFS and OS of the cohort were 1.5 months (95% CI: 1-4 months) and 19.5 months (95% CI: 11 months to not calculable), respectively. Patients harboring KIR3DL1/HLA-B genotypes predicting low affinity had a higher response rate ( p  = 0.042) and longer median PFS (3 months) than those with KIR3DL1/HLA-B genotypes predicting high affinity (1 month) ( p  = 0.0047). Cox regression analysis indicated that KIR/HLA-B genotypes were independently associated with PFS ( p  = 0.043). However, KIR/HLA-B genotypes had no impact on the OS of the cohort. The toxicity of AT treatment was mild and manageable., Conclusion: The AT regimen was well tolerated, and patients with specific KIR-HLA genotypes may benefit from this regimen.

The role of alternative polyadenylation (APA) in tumor development is becoming increasingly evident, but the impact of APA events on the prognosis of LUAD patients is unclear. Therefore, in the present study, we aimed to analyze specific APA events in LUAD to identify novel prognostic biomarkers for LUAD. We first identified prognostic candidate genes for LUAD associated with APA events and validated them in both the East Asian and the USA cohorts, finding that five genes ( DCUN1D5, PSMC4, TFAM, THRA, and TMEM100 ) were of prognostic significance in both populations. Based on this, an APA-based prognostic signature was constructed for the East Asian population. The predictive accuracy of the prognostic signature was further evaluated by the time-dependent ROC, with 1-, 2-, and 3-year AUCs of 0.86, 0.81, and 0.71, respectively. This study may provide new markers for individualized diagnosis and prognostic assessment of LUAD and potential targets for precision treatment., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Background: Long-stay nursing home (NH) residents with Alzheimer disease and related dementias (ADRD) are at high risk of hospital transfers. Machine learning might improve risk-adjustment methods for NHs., Objectives: The objective of this study was to develop and compare NH risk-adjusted rates of hospitalizations and emergency department (ED) visits among long-stay residents with ADRD using Extreme Gradient Boosting (XGBoost) and logistic regression., Research Design: Secondary analysis of national Medicare claims and NH assessment data in 2012 Q3. Data were equally split into the training and test sets. Both XGBoost and logistic regression predicted any hospitalization and ED visit using 58 predictors. NH-level risk-adjusted rates from XGBoost and logistic regression were constructed and compared. Multivariate regressions examined NH and market factors associated with rates of hospitalization and ED visits., Subjects: Long-stay Medicare residents with ADRD (N=413,557) from 14,057 NHs., Results: A total of 8.1% and 8.9% residents experienced any hospitalization and ED visit in a quarter, respectively. XGBoost slightly outperformed logistic regression in area under the curve (0.88 vs. 0.86 for hospitalization; 0.85 vs. 0.83 for ED visit). NH-level risk-adjusted rates from XGBoost were slightly lower than logistic regression (hospitalization=8.3% and 8.4%; ED=8.9% and 9.0%, respectively), but were highly correlated. Facility and market factors associated with the XGBoost and logistic regression-adjusted hospitalization and ED rates were similar. NHs serving more residents with ADRD and having a higher registered nurse-to-total nursing staff ratio had lower rates., Conclusions: XGBoost and logistic regression provide comparable estimates of risk-adjusted hospitalization and ED rates., Competing Interests: J.R.B. owns Bowblis Economic Consulting, which provides consulting services to long-term care providers. None of the material discussed in this paper is directly related to these services. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Standard drafting is an important part in the process of standard formulation and revision. By analyzing the status of the medical device industry standards drafting, thoughts and suggestions were proposed to further promote all relevant parties to actively participate in the standard drafting, effectively improve the quality of the standards, strengthen the technical support and promote the high-quality development of the industry. The statistical data of the participation of social organizations in the drafting and as the first unit drafting medical devices standards from 2017 to 2021 was researched, and the problems in the drafting of standards at this stage were analyzed. Based on the research and analyses, some thoughts and suggestions were proposed to strengthen the management of standard drafting units and promote the participation of all relevant parties in standard drafting. It is necessary to expand and enhance social participation in standard drafting further by innovating incentives, refining and strengthening normative requirements, and creating a positive social atmosphere.

Background: Gut bacteria play a crucial role in the metabolism of bile acids (BA). Whether an association exists between the fecal microbiota composition and circulating BA levels in humans is poorly understood. Here, we investigated the relationship between fecal microbiota diversity and composition with plasma levels of BA in young adults., Methods: Fecal microbiota diversity/composition was analyzed with 16S rRNA sequencing in 80 young adults (74% women; 21.9 ± 2.2 years old). Plasma levels of BA were measured using liquid chromatography-tandem mass spectrometry. PERMANOVA and Spearman correlation analyses were used to investigate the association between fecal microbiota parameters and plasma levels of BA., Results: Fecal microbiota beta (P = 0.025) and alpha diversity indexes of evenness (rho = 0.237, P = 0.033), Shannon (rho = 0.313, P = 0.004), and inverse Simpson (rho = 0.283, P = 0.010) were positively associated with plasma levels of the secondary BA glycolithocholic acid (GLCA). The relative abundance of genera belonging to the Firmicutes and Bacteroidetes phyla was positively correlated with plasma levels of GLCA (all rho ≥ 0.225, P ≤ 0.049). However, the relative abundance of species from Firmicutes and Bacteroidetes phyla were negatively correlated with plasma levels of primary and secondary BA (all rho ≤ - 0.220, P ≤ 0.045), except for the relative abundance of Bacteroides vulgatus, Alistipes onderdonkii, and Bacteroides xylanisolvens species (Bacteroidetes phylum) that were positively correlated with the plasma levels of GLCA., Conclusions: The relative abundance of specific fecal bacteria species is associated with plasma levels of BA in young adults. However, further investigations are required to validate whether the composition of the gut microbiota can regulate the plasma concentrations of BA in humans., (© 2023. The Author(s).)

Aim: This study aimed to investigate the prevalence of lateral violence (LV) experienced by nursing students during their internship, explore the difference between professional identity and professionalism among nursing students who had or had not experienced LV and analyse the mediating effect of professional identity on the relationship between LV and professionalism., Design: A cross-sectional survey was used., Methods: An online anonymous survey was distributed to nursing students (N = 298) in Jiangsu province, China from June to July 2021. The questionnaire consisted of sections on lateral violence, professional identity and nursing professionalism., Results: Approximately 49.7% of the nursing students experienced LV behaviour during the internship period. Students who experienced LV had lower professional identity and professionalism than those who did not. Among the students, LV was negatively correlated with professional identity (r = -0.333, p < 0.001) and professionalism (r = -0.418, p < 0.001). The relationship effect of LV on nursing professionalism was partly mediated by professional identity., Conclusion: Nearly half of the nursing students suffered from LV in the workplace, and this condition remarkably influenced nursing professionalism through professional identity. Both quantitative and qualitative studies are needed to investigate the factors that influence LV development in detail., (© 2022 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Purpose: High-dose methotrexate (HD-MTX)-based chemotherapy regimen is the first-line option for primary central nervous system lymphoma (PCNSL). This prospective cohort study aimed to evaluate the efficacy and adverse effects of HD-MTX plus idarubicin (IDA) in patients with newly diagnosed immunocompetent PCNSL., Methods: We recruited newly diagnosed PCNSL patients from January 2017 to August 2020. Patients were assigned into two groups: HD-MTX monotherapy and HD-MTX plus IDA (HD-MTX/IDA). In the HD-MTX monotherapy group, patients were treated with MTX 8 g/m 2 alone on day 1, while the HD-MTX/IDA group received MTX 8 g/m 2 on day 1 and IDA 10 mg/m 2 on day 2. Treatments were repeated every 3 weeks for 8 cycles except for progression and/or unacceptable toxicity., Results: We recruited 61 PCNSL patients, including 36 in the HD-MTX and 25 in the HD-MTX/IDA group. The CR rate was 68% in the HD-MTX/IDA group and 72.22% of patients in the HD-MTX monotherapy group (p = 0.7221), while the overall response rate was 72% vs. 77.78% (p = 0.6063). Median PFS in HD-MTX/IDA group and HD-MTX monotherapy group were 15.6 months and 18.5 months, respectively (p = 0.6374). Median OS was not reached in both groups. There were no significant differences in adverse effects between the two groups., Conclusions: The combination of IDA with HD-MTX showed no obvious therapeutic advantage over HD-MTX monotherapy in newly diagnosed patients with PCNSL. HD-MTX dose of 8 g/m 2 monotherapy can still provide better therapeutic benefits in patients with acceptable adverse effects. Future studies could explore HD-MTX in combination with other chemotherapeutic agents in the first-line treatment of PCNSL., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The associations of multimorbidity patterns with transitions between frailty states remain unclear in older individuals., Methods: We used data from the National Health and Aging Trends Study 2011-2019. Frailty was measured annually using the Fried frailty phenotype. Multimorbidity patterns at baseline were identified using latent class analysis based on 14 chronic conditions. We used the semi-Markov multi-state model to investigate the influences of multimorbidity characterized by condition counts and patterns on subsequent frailty transitions over follow-ups., Results: Among 9450 participants aged ≥65 years at baseline, 34.8% were non-frail, 48.1% were pre-frail and 17.0% were frail. Over a median follow-up of 4.0 years, 16 880 frailty transitions were observed, with 10 527 worsening and 6353 improving. For 7675 participants with multimorbidity, four multimorbidity patterns were identified: osteoarticular pattern (62.4%), neuropsychiatric-sensory pattern (17.2%), cardiometabolic pattern (10.3%) and complex multimorbidity pattern (10.1%). Compared with no disease, multimorbidity was significantly associated with an increased risk of worsening transitions, including from non-frail to pre-frail (hazard ratio [HR] = 1.35; 95% confidence interval [CI] = 1.21-1.52), from non-frail to frail (HR = 1.68; 95% CI = 1.04-2.73), from pre-frail to frail (HR = 2.19; 95% CI = 1.66-2.90) and from pre-frail to death (HR = 1.64; 95% CI = 1.11-2.41). Compared with the osteoarticular pattern, neuropsychiatric-sensory, cardiometabolic and complex multimorbidity patterns had a significantly higher risk of worsening frailty (all P < 0.05)., Conclusions: Multimorbidity was associated with dynamic transitions between frailty states and death among older American adults, and the associations varied across multimorbidity patterns. The findings could offer significant implications for public health policymakers in planning interventions and healthcare resources. They also might inform clinicians regarding providing targeted clinical treatment and health management based on multimorbidity patterns of older people., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Although cross-sectional studies on the learning status of nursing undergraduates during the COVID-19 epidemic have surged, few studies have explored the normalization of COVID-19 on students' learning burnout and mental health. The study was designed to investigate the learning burnout of nursing undergraduates in school under the normalization of the COVID-19 epidemic and explore the hypothesized mediation effect of academic self-efficacy in the relationship between anxiety, depression and learning burnout in Chinese nursing undergraduates., Methods: A cross-sectional study was conducted among nursing undergraduates in the school of nursing of a university in Jiangsu Province, China ( n = 227). A general information questionnaire, College Students' Learning Burnout Questionnaire, Generalized Anxiety Disorder Scale (GAD-7), and Patient Health Questionnaire depression scale (PHQ-9) were administered. Descriptive statistical analysis, Pearson correlation analysis, and multiple linear regression analysis were performed via SPSS 26.0. Process plug-in (Model 4) was used to test the mediating effect of academic self-efficacy (bootstrap 5000 iterations, α = 0.05)., Results: Learning burnout (54.1 ± 0.656) was positively correlated with anxiety (4.6 ± 0.283) and depression (5.3 ± 0.366) ( p < 0.01) and was negatively correlated with academic self-efficacy (74.41 ± 0.674) ( p < 0.01). Academic self-efficacy plays a mediating role between anxiety and learning burnout (0.395/0.493, 80.12%) and a mediating role between depression and learning burnout (0.332/0.503, 66.00%)., Conclusion: Academic self-efficacy has a significant predictive effect on learning burnout. Schools and teachers should strengthen the screening and counselling of students' psychological problems, detect learning burnout caused by emotional problems in advance and improve students' initiative and enthusiasm for learning.

Objective: To examine whether increases in physician volume in primary healthcare facilities are associated with reduced utilisation of hospital outpatient and inpatient services after China facilitated the establishment of the hierarchical medical system., Design: We used a two-way fixed-effects regression to examine the association between the annual number of physicians in primary healthcare facilities and that of patient visits per physician, inpatient admissions and total expenses per outpatient visit in public hospitals during 2010-2014 and 2015-2019. Variables were log transformed to ensure the normal distribution of the data., Setting: Province-level data of all 31 provinces in mainland China from 2010 to 2019 were collected from the China Health Statistics Yearbook published by the China Health Commission., Participants: All 31 provinces in mainland China., Primary and Secondary Outcome Measures: The annual number of outpatient visits per physician, hospital admission and total expenses per outpatient visit in public hospitals., Results: During 2015-2019, we found that, on average, a 1% increase in the number of primary healthcare physicians was accompanied by a 0.19% (95% CI -0.33% to -0.05%) reduction in the annual number of visits per physician in public hospitals, and a 0.31% (95% CI -0.52% to -0.10%) reduction in patient visits in city-administered hospitals. No significant associations were found between 2010 and 2014. We also did not observe any significant associations between primary healthcare physician volume and hospital admissions or outpatient expenses during neither 2010-2014 and 2015-2019., Conclusions: In the context of the hierarchical medical system, enhancing physician volume in primary healthcare facilities helps reduce outpatient visits in public hospitals, especially city-administered hospitals. However, more efforts are required to be continuously made to improve primary healthcare capacity to avoid preventable hospital admissions and outpatient expenses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To provide context for evaluating proposed nursing home staff regulations, we examined the proportion of facility revenues spent on nursing staff, as well as nursing staff levels in hours worked and paid per resident day, in 2019. Nationally, the median proportion of revenues spent on nursing staff was 33.9 percent, and median nursing staff levels were 3.67 hours worked and 4.08 hours paid per resident day. Facilities with higher shares of Medicaid residents spent a larger share of revenues on nursing staff but had lower staffing levels. States varied significantly with respect to median spending on nursing staff (26.8-44.0 percent of revenues) and median nursing staff levels (3.2-5.6 hours worked and 3.6-5.7 hours paid per resident day). These findings indicate that raising the proportion of revenues spent by nursing homes on nursing staff to a regulated minimum would not guarantee the achievement of adequate nursing staff levels unless it was paired with other regulatory mechanisms.

Purpose: Providing a geriatric assessment (GA) summary with management recommendations to oncologists reduces clinician-rated toxicity in older patients with advanced cancer receiving treatment. This secondary analysis of a national cluster randomized clinical trial (ClinicalTrials.gov identifier: NCT02054741) aims to assess the effects of a GA intervention on symptomatic toxicity measured by Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)., Methods: From 2014 to 2019, the study enrolled patients age ≥ 70 years, with advanced solid tumors or lymphoma and ≥ 1 GA domain impairment, who were initiating a regimen with high prevalence of toxicity. Patients completed PRO-CTCAEs, including the severity of 24 symptoms (11 classified as core symptoms) at enrollment, 4-6 weeks, 3 months, and 6 months. Symptoms were scored as grade ≥ 2 (at least moderate) and grade ≥ 3 (severe/very severe). Symptomatic toxicity was determined by an increase in severity during treatment. A generalized estimating equation model was used to assess the effects of the GA intervention on symptomatic toxicity., Results: Mean age was 77 years (range, 70-96 years), 43% were female, and 88% were White, 59% had GI or lung cancers, and 27% received prior chemotherapy. In 706 patients who provided PRO-CTCAEs at baseline, 86.1% reported at least one moderate symptom and 49.7% reported severe/very severe symptoms at regimen initiation. In 623 patients with follow-up PRO-CTCAE data, compared with usual care, fewer patients in the GA intervention arm reported grade ≥ 2 symptomatic toxicity (overall: 88.9% v 94.8%, P = .035; core symptoms: 83.4% v 91.7%, P = .001). The results for grade ≥ 3 toxicity were comparable but not significant ( P > .05)., Conclusion: In the presence of a high baseline symptom burden, a GA intervention for older patients with advanced cancer reduces patient-reported symptomatic toxicity.

Many nursing homes operated at thin profit margins prior to the COVID-19 pandemic. This study examines the role of nursing homes' financial performance and chain affiliation in shortages of personal protection equipment (PPE) during the first year of the COVID-19 pandemic. We constructed a longitudinal file of 79 868 nursing home-week observations from 10 872 unique facilities. We found that a positive profit margin was associated with a 21.0% lower probability of reporting PPE shortages in chain-affiliated nursing homes, but not in non-chain nursing homes. Having adequate financial resources may help nursing homes address future emergencies, especially those affiliated with a multi-facility chain., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JRB provides consulting services to various health care and long-term care stakeholders, including government agencies and providers. The other authors declare no conflicts of interest.

Aim: To explore anxiety, sleep quality, and mindfulness of frontline nurses at the initial epicenter of the pandemic, to examine the mediating effects of mindfulness., Background: COVID-19 was first identified in Wuhan, China in January 2020. Nurses were at the forefront of care and treatment across hospitals in response to the pandemic., Methods: Single site cross-sectional survey conducted in Wuhan province (China) between March and April in 2020. Quantitative analysis of survey data from N118 nurses working in the frontline COVID response. Questionnaires included: The general information questionnaire, the Self-Anxiety Scale, the Short Inventory of Mindfulness, and the Pittsburgh Sleep Quality Index., Results: Front-line nurses' anxiety was positively associated with sleep quality and mindfulness was negatively associated with anxiety and sleep quality. Mindfulness had a mediating role on anxiety and sleep quality, with intermediary adjustment effects (ES = 0.136, 95 % CI 0.02 to 0.26), accounting for 21.9 % of the total effect ratio., Conclusions: Anxiety causes a reduction in sleep quality and mindfulness can help with anxiety. Mindfulness strategies may help during periods of higher anxiety in the workplace; however, other factors must be considered. Further research is required on strategies for assisting nurses during periods of extreme anxiety., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication., (Copyright © 2022. Published by Elsevier Inc.)

Pre-clinical studies suggest that circulating oxylipins, i.e., the oxidation products of polyunsaturated fatty acids (PUFAs), modulate gut microbiota composition in mice, but there is no information available in humans. Therefore, this study aimed to investigate the relationship between omega-3 and omega-6 derived oxylipins plasma levels and fecal microbiota composition in a cohort of young adults. 80 young adults (74% women; 21.9 ± 2.2 years old) were included in this cross-sectional study. Plasma levels of oxylipins were measured using liquid chromatography-tandem mass spectrometry. Fecal microbiota composition was analyzed by V3-V4 16S rRNA gene sequencing. We observed that plasma levels of omega-3 derived oxylipins were positively associated with the relative abundance of Clostridium cluster IV genus ( Firmicutes phylum; rho ≥ 0.415, p ≤ 0.009) and negatively associated with the relative abundance of Sutterella genus (Proteobacteria phylum; rho ≥ -0.270, p ≤ 0.041), respectively. Moreover, plasma levels of omega-6 derived oxylipins were negatively associated with the relative abundance of Acidaminococcus and Phascolarctobacterium genera ( Firmicutes phylum; all rho ≥ -0.263, p ≤ 0.024), as well as Sutterella , Succinivibrio , and Gemmiger genera ( Proteobacteria phylum; all rho ≥ -0.263, p ≤ 0.024). Lastly, the ratio between omega-6 and omega-3 oxylipins plasma levels was negatively associated with the relative abundance of Clostridium cluster IV genus ( Firmicutes phylum; rho = -0.334, p = 0.004) and Butyricimonas genus ( Bacteroidetes phylum; rho = -0.292, p = 0.014). In conclusion, our results show that the plasma levels of omega-3 and omega-6 derived oxylipins are associated with the relative abundance of specific fecal bacteria genera.

Background: Alternative polyadenylation (APA) events may be modulated by single nucleotide polymorphisms (SNPs). Therefore, this study aims to evaluate the association between APA quantitative trait loci (apaQTLs)-related SNPs (apaQTL-SNPs) and non-small-cell lung cancer (NSCLC) risk. Methods: APA-related genes associated with NSCLC (LUAD and LUSC) were first identified, and the respective apaQTL-SNPs of those genes were selected. Then, a two-phase case-control study was performed to evaluate the association between candidate apaQTL-SNPs and NSCLC risk. Results: A total of 7 LUAD- and 21 LUSC-associated apaQTL-SNPs were selected. In the first phase, the apaQTL-SNP rs10138506 was significantly associated with LUAD risk (p < 0.05), whereas the other two apaQTL-SNPs (rs1130698 and rs1130719) were significantly associated with LUSC risk (p < 0.05). In the second phase, the variant G allele of rs10138506 was still significantly associated with an increased risk of LUAD (OR = 1.42, 95%CI = 1.02−1.98, p = 0.038). Functional annotation indicated that the variant G allele of rs10138506 was significantly associated with a higher PDUI value of CHURC1. Meanwhile, 3′RACE experiments verified the presence of two poly(A) sites (proximal and distal) in CHURC1, while qRT-PCR results indicated that different genotypes of rs1127968 which, in perfect LD with rs10138506, can mediate changes in the lengths of the 3′UTR of CHURC1 isoforms. Conclusion: The variant G allele of rs10138506 in CHURC1 was correlated with a longer 3′UTR of CHURC1 mRNA and an increased LUAD risk. Further studies should evaluate the interaction between rs10138506 and different 3′UTR lengths of CHURC1 that regulate LUAD development.

Purpose: Falls are a modifiable source of morbidity for older adults with cancer, yet are underassessed in oncology practice. In this secondary analysis of a nationwide cluster-randomized controlled trial, we examined characteristics associated with patient-oncologist conversations about falls, and whether oncologist knowledge of geriatric assessment (GA) resulted in more conversations., Methods: Eligible patients (ClinicalTrials.gov identifier: NCT02107443) were age ≥ 70 years, had stage III/IV solid tumor or lymphoma, were being treated with noncurative treatment intent, and ≥ 1 GA domain impairment. Patients in both arms underwent GA. At practices randomly assigned to the intervention arm, oncologists were provided a GA summary with management recommendations. In both arms, patients had one clinical encounter audio-recorded, transcribed, and coded to categorize whether a conversation about falls occurred. Generalized linear mixed models adjusted for arm, practice site, and other important covariates were used to generate proportions and odds ratios (ORs) from the full sample., Results: Of 541 patients (intervention N = 293 and usual care N = 248, mean age: 77 years, standard deviation: 5.3), 528 had evaluable audio recordings. More patients had conversations about falls in the intervention versus usual care arm (61.3% v 10.3%, P < .001). Controlling for the intervention and practice site, history of falls (OR, 2.1; 95% CI, 1.3 to 3.6; P = .005) and impaired physical performance (OR, 4.7; 95% CI, 1.7 to 12.8; P = .002) were significantly associated with patient-oncologist conversations about falls., Conclusion: GA intervention increased conversations about falls. History of falls and impaired physical performance were associated with patient-oncologist conversations about falls in community oncology practice.

Exercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n = 31, and VIG-EX; n = 31). We observed no changes in BAT volume (Δ Control: -22.2 ± 52.6 ml; Δ MOD-EX: -15.5 ± 62.1 ml, Δ VIG-EX: -6.8 ± 66.4 ml; P = 0.771) or 18 F-fluorodeoxyglucose uptake (SUVpeak Δ Control: -2.6 ± 3.1 ml; Δ MOD-EX: -1.2 ± 4.8, Δ VIG-EX: -2.2 ± 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults., (© 2022. The Author(s).)

Problem: Fear of hypoglycemia is a significant concern for parents of children/ adolescents with type 1 diabetes. Although some studies have explained the parental fear of hypoglycemia, the related factors were yet to be determined. This systematic review aims to identify the related factors of fear of hypoglycemia in the parents of children and adolescents with type 1 diabetes and provide a theoretical basis for further intervention., Eligibility Criteria: PubMed, MEDLINE, EMBASE, Scopus, CINAHL, EBSCO, Web of Science, and Cochrane Library were systematically searched from 2010 to 2021. Studies evaluating the fear of hypoglycemia of parents and its associated factors were included., Sample: Twenty-three observational articles met the criteria., Results: Significant associations were found between fear of hypoglycemia and specific factors, including motherhood, nocturnal hypoglycemia, and the number of blood glucose monitoring. Psychological factors, including anxiety, depression, pediatric parenting stress, mindfulness, self-efficacy, quality of life, and sleep disorders, were conclusive and associations with parental fear of hypoglycemia., Conclusions: Understanding parental fear of hypoglycemia can help parents prevent potential problems in diabetes management, thus promoting children's growth. According to current evidence, effective targeted interventions based on modifiable relevant factors can be developed to reduce the fear of hypoglycemia in parents while maintaining optimal blood glucose control in children/ adolescents., Implications: Health professionals should pay more attention to the mental health of parents, and parents should be involved in the care plan and have the opportunity to discuss their fear of hypoglycemia in the most appropriate way to manage type 1 diabetes., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pressure injury (PI) prevention is a huge industry and involves various interventions. Temperature and moisture are important factors for wound healing; however, the active mechanism by which “moist heat” affects PI prevention has not yet been clarified. Thus, we explored the protective and therapeutic effects of hydrotherapy on PI based on the preconditioning (PC) principle, which might be useful for clinical practice. This study aimed to investigate the preventive mechanisms of heat shock preconditioning on PIs in rat models. The experiment was performed in the basic medical laboratory of Nagano College of Nursing in Japan. Ten rats were divided into two groups, with five rats in each group. Rats in the control group were not bathed. Rats in the preconditioning group (PC group) were bathed with hot tap-water. Bathing was conducted thrice a week. After bathing for 4 weeks, the PI model was constructed on the rats’ dorsal skin. The skin temperature, skin moisture, and area of ulcers were compared between the two groups. In vitro, we investigated the expression of heat shock protein 27 (Hsp27) in 6, 12, and 24 h after the PI model was constructed through Western blot analysis. Ulcers occurred in the control group 24 h after the PI model constructed, wheras the PC group exhibited ulcers after 36 h. The ulcer area was larger in the control group than that in the PC group after 24 h (all p < 0.05). The temperatures of PI wounds in the control group decreased and were lower than those in the PC group after 1, 6, 12, 36, and 48 h (all p < 0.05). However, the skin moisture levels of PI wounds increased in the control group and were higher than those in the PC group at the same time (all p < 0.05). Using Western blot analysis, hydrotherapy preconditioning showed the potential to increase Hsp27 expression after pressure was released (p < 0.05). We determine that heat shock preconditioning had a preventive effect on PIs in rat models, a result that may be associated with their actions in the upregulation of Hsp27.

Liver hepatocellular carcinoma (LIHC) is a malignant cancer with widespread prevalence. The suppressive immune environment causes largely refractory to current treatment. The protein regulator of cytokinesis 1 (PRC1) is an essential gene for cytokinesis and is involved in cancer pathogenesis. However, the functions of PRC1 have been barely clarified, especially in LIHC. Here, we investigated the expression, prognostic value, and functions of PRC1 in LIHC. Pan-cancer analysis revealed the overexpression of PRC1 in the Cancer Genome Atlas (TCGA) database. Four LIHC datasets from the Gene Expression Omnibus (GEO) database confirmed the PRC1 overexpression in LIHC. The mRNA and protein levels of PRC1 in LIHC cells were higher than in normal liver cells. The overexpression of PRC1 predicted progressed clinical stage and poor prognosis of LIHC. We further investigated the functions of PRC1 by performing the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and Gene Set Enrichment Analysis (GSEA) of its coexpressing genes. High PRC1 expression was associated with increased genome instability of LIHC. Moreover, PRC1 was positively correlated with the infiltration of suppressive immune cells like T regulatory cells (Tregs) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and was negatively correlated with the effector immune cells' infiltration, including B cells and CD8+ T cells. In addition, PRC1 was positively correlated with the expression of tumor immune checkpoint molecules. Taken together, PRC1 overexpression contributes to the genome instability and the suppressive immune microenvironment of LIHC. Thus, PRC1 has the potential to be a prognostic marker and therapeutic target of LIHC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Canjing Zhang et al.)

Purpose: Prior cancer research is limited by inconsistencies in defining rurality. The purpose of this study was to describe the prevalence of cancer risk factors and cancer screening behaviors across various county-based rural classification codes, including measures reflecting a continuum, to inform our understanding of cancer disparities according to the extent of rurality., Methods: Using an ecological cross-sectional design, we examined differences in cancer risk factors and cancer screening behaviors from the Behavioral Risk Factor Surveillance System and National Health Interview Survey (2008-2013) across rural counties and between rural and urban counties using four rural-urban classification codes for counties and county-equivalents in 2013: U.S. Office of Management and Budget, National Center for Health Statistics, USDA Economic Research Service's rural-urban continuum codes, and Urban Influence Codes., Results: Although a rural-to-urban gradient was not consistently evident across all classification codes, the prevalence of smoking, obesity, physical inactivity, and binge alcohol use increased (all p trend  < 0.03), while colorectal, cervical and breast cancer screening decreased (all p trend  < 0.001) with increasing rurality. Differences in the prevalence of risk factors and screening behaviors across rural areas were greater than differences between rural and urban counties for obesity (2.4% vs. 1.5%), physical activity (2.9% vs. 2.5%), binge alcohol use (3.4% vs. 0.4%), cervical cancer screening (6.8% vs. 4.0%), and colorectal cancer screening (4.4% vs. 3.8%)., Conclusions: Rural cancer disparities persist across multiple rural-urban classification codes, with marked variation in cancer risk factors and screening evident within rural regions. Focusing only on a rural-urban dichotomy may not sufficiently capture subpopulations of rural residents at greater risk for cancer and cancer-related mortality., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: Nursing homes (NHs) in micropolitan areas are reported to have different facility and market factors than urban NHs, but how these factors contribute to differences in emergency department (ED) visits remains unknown. This study examined and quantified sources of micropolitan-urban differences in NH risk-adjusted rates of any ED visit, ED without hospitalization or observation stay (outpatient ED), and potentially avoidable ED (PAED) visits of long-stay residents., Design: The 2011-2013 national Medicare claims and NH Minimum Data Set (MDS) 3.0 were analyzed. We implemented generalized estimating equation models to examine micropolitan-urban differences in ED rates and Blinder-Oaxaca decompositions to quantify the contributions of NH and market factors., Setting and Participants: The study cohort included 12,883 unique privately owned, freestanding NHs from urban and micropolitan areas., Measures: Quarterly risk-adjusted rates of any ED visits, outpatient ED visits, and PAED visits were calculated from Medicare claims and MDS. NH and market characteristics were extracted from the Certification And Survey Provider Enhanced Reporting and Area Health Resources File., Results: Over the study period, risk-adjusted rates averaged 10.2%, 3.4%, and 3.3% for any ED, outpatient ED, and PAED visits, respectively. Compared with urban NHs, micropolitan NHs reported similar rates of any ED, but significantly higher rates of outpatient ED and PAED (β = 0.20% and 0.27%; both P < .05). Observable differences in NH characteristics (eg, number of beds, percentage Medicare or Medicaid residents, and employment of nurse practitioners and physician assistants) explained more than 20% of the micropolitan-urban differences in rates of outpatient ED and PAED visits; market factors (mainly Medicare Advantage penetration) explained about 46% of the differences in rates of outpatient ED visits., Conclusions and Implications: Compared with urban NHs, micropolitan NHs tend to utilize more avoidable emergency care that can be partially explained by facility size, payer mix, use of nurse practitioners and physician assistants, and market structure., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Vision impairment has become a prominent public health issue worldwide. However, little is known about vision impairment prevalence trends among the oldest-old adults in China. This study aimed to examine 20-year trends in the prevalence of vision impairment among the oldest-old Chinese adults and explore the contributions of sociodemographic variables, health behaviours, and chronic conditions to the trends., Methods: This retrospective longitudinal study used data from the Chinese Longitudinal Healthy Longevity Survey during 1998-2018. A total of 45 849 participants aged ≥80 years at study entry were included. Vision impairment was assessed by an adapted Landolt-C chart at each wave. We examined unadjusted and adjusted nonlinear trends using generalized estimating equation models incorporating a natural cubic spline. We conducted linear regression models to estimate absolute annual prevalence changes and determine the contributions of sociodemographic variables, health behaviours, and chronic conditions to the trends., Results: The fully adjusted prevalence doubled from 5.5% (95% confidence interval (CI) = 5.1%-6.0%) in 1998 to 10.7% (95% CI = 9.9%-11.5%) in 2011 and slightly increased to 11.1% (95% CI = 10.3%-12.0%) in 2018 among the oldest-old Chinese population. Glaucoma, cataracts, cognitive impairment, hearing impairment, and urban residence were significant contributors to changes in vision impairment prevalence during 1998-2018. Differences in vision impairment prevalence associated with glaucoma and cataracts narrowed since 2005. Disparities in the trends among cognitively impaired and unimpaired older adults remained unchanged over time. Similar results were observed in older people with and without hearing impairment., Conclusions: Vision impairment prevalence among the oldest-old Chinese population increased from 1998 to 2011 and remained stable from 2011 to 2018. Future work is needed to improve the prevention and management of chronic diseases associated with vision impairment to reduce its prevalence., Competing Interests: Disclosure of interest: The authors completed the ICMJE Declaration of Interest Form (available upon request from the corresponding author) and disclose no relevant interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Inflammation and fibrosis are the important pathophysiologic processes in diabetic kidney disease (DKD), which is induced by epigenetics, especially histone posttranslational modification (HPTMs). Recent reports highlighted that butyrate, one of the short-chain fatty acids (SCFAs) primarily originated from the fermentation of dietary fiber in the gut, attenuates inflammation and fibrosis in the prevention and treatment of DKD; however, the molecular mechanisms are still unclear. Histone lysine butyrylation (Kbu), a novel histone modification marker induced by butyrate, has been found to be involved in the regulation of pathophysiological processes. To reveal the mechanisms of butyrate-induced histone (Kbu), in the prevention and treatment of DKD, both DKD models in vivo and in vitro were treated with sodium butyrate (NaB). Our results confirmed that exogenous NaB improved the disorder of glucose and lipid metabolism, prevented proteinuria and renal failure, and inhibited renal inflammation and fibrosis. Meanwhile, NaB also induced histone Kbu and H3K9 butyrylation (H3K9bu) in vivo and in vitro ; however, inhibition of histone Kbu with the histone modification enzyme p300 inhibitor A485 reversed the anti-inflammatory and anti-fibrosis effects of NaB. In conclusion, our data reveal that NaB antagonizes renal inflammatory and fibrosis injury and attenuates DKD possibly via histone Kbu, suggesting that butyrate-induced histone Kbu or H3K9bu may be an important molecular mechanism in the pathogenesis and treatment of DKD., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Tingting Zhou et al.)

Background: Prior evidence suggests that capsinoids ingestion may increase resting energy expenditure (EE) and fat oxidation (FATox), yet whether they can modulate those parameters during exercise conditions remains poorly understood. We hypothesized that dihydrocapsiate (DHC) ingestion would increase EE and specifically FATox during an acute bout of aerobic exercise at FATmax intensity (the intensity that elicits maximal fat oxidation during exercise [MFO]) in men with overweight/obesity. Since FATmax and MFO during aerobic exercise appear to be indicators of metabolic flexibility, whether DHC has an impact on FATox in this type of population is of clinical interest., Methods: A total of 24 sedentary men (age = 40.2 ± 9.2 years-old; body mass index = 31.6 ± 4.5 kg/m 2 [n = 11 overweight, n = 13 obese]) participated in this randomized, triple-blinded, placebo-controlled, crossover trial (registered under ClinicalTrials.gov Identifier no. NCT05156697). On the first day, participants underwent a submaximal exercise test on a cycle ergometer to determine their MFO and FATmax intensity during exercise. After 72 hours had elapsed, the participants returned on 2 further days (≥ 72 hours apart) and performed a 60 min steady-state exercise bout (i.e. cycling at their FATmax, constant intensity) after ingesting either 12 mg of DHC or placebo; these conditions were randomized. Respiratory gas exchange was monitored by indirect calorimetry. Serum marker concentrations (i.e. glucose, triglycerides, non-esterified fatty acids (NEFAs), skin temperature, thermal perception, heart rate, and perceived fatigue) were assessed., Results: There were no significant differences (P > 0.05) between DHC and placebo conditions in the EE and FATox during exercise. Similarly, no significant changes were observed in glucose, triglycerides, or NEFAs serum levels, neither in the skin temperature nor thermal perception across conditions. Heart rate and perceived fatigue did not differ between conditions., Conclusions: DHC supplementation does not affect energy metabolism during exercise in men with overweight/obesity., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Introduction: Caregiver-oncologist concordance regarding the patient's prognosis is associated with worse caregiver outcomes (e.g., depressive symptoms), but mechanisms underpinning these associations are unclear. We explored whether caregiving esteem mediates these associations., Methods: At enrollment, caregivers and oncologists used a 5-point ordinal scale to estimate patient survival; identical responses were considered concordant. At 4-6 weeks, caregivers completed an assessment of the extent to which caregiving imparts self-esteem (Caregiver Reaction Assessment self-esteem subscale; range 0-5; higher score indicates greater esteem). They also completed Patient Health Questionnaire-2 (PHQ-2) for depressive symptoms, Distress Thermometer, and 12-Item Short Form Survey for quality of life (QoL). Mediation analysis with bootstrapping (PROCESS macro by Hayes) was used to estimate the extent to which caregiving mediated the effects of prognostic concordance on caregiver outcomes through caregiving esteem., Results: Prognostic concordance occurred in 28% the caregiver-oncologist dyads; 85% of the discordance were due to caregivers estimating a longer patient's survival. At 4-6 weeks, mean caregiving esteem score was 4.4 (range 1.5-5.0). Lower caregiving esteem mediated the associations of concordance with higher PHQ-2 [indirect effect = 0.12; 95% Confidence Interval (CI) 0.03, 0.27], greater distress (indirect effect =0.25; 95% CI 0.08, 0.48), and poorer QoL (indirect effect = -1.50; 95% CI -3.06, -0.41). Caregiving esteem partially mediated 39%, 64%, and 48% of the associations between caregiver-oncologist concordance and PHQ-2, distress, and SF-12, respectively., Conclusions: Caregiver-oncologist concordance was associated with lower caregiving esteem. Lower caregiving esteem mediated the negative relationship between caregiver-oncologist concordance and caregiver outcomes., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Nursing homes (NHs) are serving an increasing proportion of residents with cognitive issues (e.g., dementia) and mental health conditions. This study aims to: (1) implement unsupervised machine learning to cluster NHs based on residents' dementia and mental health conditions; (2) examine NH staffing related to the clusters; and (3) investigate the association of staffing and NH quality (measured by the number of deficiencies and deficiency scores) in each cluster., Data Sources: 2009-2017 Certification and Survey Provider Enhanced Reporting (CASPER) were merged with LTCFocUS.org data on NHs in the United States., Study Design: Unsupervised machine learning algorithm (K-means) clustered NHs based on percent residents with dementia, depression, and serious mental illness (SMI, e.g., schizophrenia, anxiety). Panel fixed-effects regressions on deficiency outcomes with staffing-cluster interactions were conducted to examine the effects of staffing on deficiency outcomes in each cluster., Data Extraction Methods: We identified 110,463 NH-year observations from 14,671 unique NHs using CASPER data., Principal Findings: Three clusters were identified: low dementia and mental illnesses (Postacute Cluster); high dementia and depression, but low SMI (Long-stay Cluster); and high dementia and mental illnesses (Cognitive-mental Cluster). From 2009 to 2017, the number of Postacute Cluster NHs increased from 3074 to 5719, while the number of Long-stay Cluster NHs decreased from 6745 to 3058. NHs in Long-stay/Cognitive-mental Clusters reported slightly lower nursing staff hours in 2017. Regressions suggested the effect of increasing staffing on reducing deficiencies is statistically similar across NH clusters. For example, 1 hour increase in registered nurse hours per resident day was associated with -0.67 (standard error [SE] = 0.11), -0.88 (SE = 0.12), and -0.97 (SE = 0.15) deficiencies in Postacute Cluster, Long-stay Cluster, and Cognitive-mental Cluster, respectively., Conclusions: Unsupervised machine learning detected a changing landscape of NH serving residents with dementia and mental illnesses, which requires assuring staffing levels and trainings are suited to residents' needs., (© 2021 Health Research and Educational Trust.)

This perspectives paper provides an overview of how to read and interpret a Sankey, examples using symptom data from older adults with advanced cancer, a synopsis of medical literature, and comments on creating and using the diagram for presentation of data. From prior reports and our own, we conclude Sankeys are an excellent tool for visualizing the changing status of older patients with cancer. Older adult symptom data is used as an example with data dispalyed in a range of Sankey flow diagrams. Because there is large heterogeneity in aging, different subgroups can be examined. In a single diagram, Sankey can show both the likelihood and variability of patients' future status from their current status., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the association of plasma levels of endocannabinoids with fecal microbiota., Methods: Plasma levels of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), as well as their eleven analogues, and arachidonic acid (AA), were measured using liquid chromatography-tandem mass spectrometry in 92 young adults. DNA extracted from stool samples was analyzed using 16S rRNA gene sequencing. Lipopolysaccharide levels were measured in plasma samples., Results: Plasma levels of endocannabinoids and their analogues were not related to beta or alpha diversity indexes. Plasma levels of AEA and related N-acylethanolamines correlated positively with the relative abundance of Faecalibacterium genus (all rho ≥ 0.26, p ≤ 0.012) and Akkermansia genus (all rho ≥ 0.22, p ≤ 0.036), and negatively with the relative abundance of Bilophila genus (all rho ≤ -0.23, p ≤ 0.031). Moreover, plasma levels of 2-AG and other acylglycerols correlated positively with the relative abundance of Parasutterella (all rho ≥ 0.24, p ≤ 0.020) and Odoribacter genera (all rho ≥ 0.27, p ≤ 0.011), and negatively with the relative abundance of Prevotella genus (all rho ≤ -0.24, p ≤ 0.023). In participants with high lipopolysaccharide values, the plasma levels of AEA and related N-acylethanolamines, as well as AA and 2-AG, were negatively correlated with plasma levels of lipopolysaccharide (all rho ≤ -0.24, p ≤ 0.020)., Conclusion: Plasma levels of endocannabinoids and their analogues are correlated to specific fecal bacterial genera involved in maintaining gut barrier integrity in young adults. This suggests that plasma levels of endocannabinoids and their analogues may play a role in the gut barrier integrity in young adults.

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive subtype of non-Hodgkin lymphoma. Gemcitabine, oxaliplatin, and L-asparaginase (GELOX) is one of the first-line chemotherapy regimens of NKTCL. Yet, the prognosis of NKTCL is poor. Icaritin is an herb-derived monomer from icariin with antitumor effects. We found that icaritin induced proliferation inhibition and apoptosis of NKTCL both in vitro and in vivo . Moreover, icaritin inhibited the dissemination of NKTCL in vivo . RNA sequencing revealed the Polo-like kinase 1 (PLK1) gene and DNA damage response (DDR) as the targets of icaritin. Mechanistically, icaritin inhibited PLK1 to promote checkpoint kinase 2 (Chk2) homodimerization and its T387 phosphorylation, which further activated p53, leading to the activation of the DDR pathway. Moreover, inhibiting PLK1 increased Forkhead box O3a nuclear localization, the latter of which activated ataxia telangiectasia mutated (ATM), an early sensor of DNA damage. Then ATM phosphorylated Chk2 T68 and initiated Chk2 activation. Remarkably, the combined treatment of icaritin and GELOX achieved better antitumor efficacy than single treatment in vivo . In summary, our results proved the efficacy of icaritin treating NKTCL, provided insights into its antitumor molecular mechanism, and revealed the application value of icaritin in facilitating clinical NKTCL treatment., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Objective: This study aimed to develop and validate a multimorbidity index using self-reported chronic conditions for predicting 5-year mortality risk., Methods: We analyzed data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) and included 11,853 community-dwelling older adults aged 65-84 years. Restrictive association rule mining (ARM) was used to identify disease combinations associated with mortality based on 13 chronic conditions. Data were randomly split into the training ( N = 8,298) and validation ( N = 3,555) sets. Two multimorbidity indices with individual diseases only (MI) and disease combinations (MIDC) were developed using hazard ratios ( HR s) for 5-year morality in the training set. We compared the predictive performance in the validation set between the models using condition count, MI, and MIDC by the concordance (C) statistic, the Integrated Discrimination Improvement (IDI), and the Net Reclassification Index (NRI)., Results: A total of 13 disease combinations were identified. Compared with condition count (C-statistic: 0.710), MIDC (C-statistic: 0.713) showed significantly better discriminative ability (C-statistic: p = 0.016; IDI: 0.005, p < 0.001; NRI: 0.038, p = 0.478). Compared with MI (C-statistic: 0.711), the C-statistic of the model using MIDC was significantly higher ( p = 0.031), while the IDI was more than 0 but not statistically significant (IDI: 0.003, p = 0.090)., Conclusion: Although current multimorbidity status is commonly defined by individual chronic conditions, this study found that the multimorbidity index incorporating disease combinations showed supreme performance in predicting mortality among community-dwelling older adults. These findings suggest a need to consider significant disease combinations when measuring multimorbidity in medical research and clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Huang, Liu, Xu, Su, Chen, Hu and Xu.)

Background: Risk prediction models that estimate patient probabilities of adverse events are commonly deployed in bariatric surgery. The objective was to validate a machine learning (Super Learner) prediction model of 30-day readmission after bariatric surgery in comparison with a traditional logistic regression., Methods: This prognostic study for validation of risk prediction models used data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program. Patients who underwent elective laparoscopic gastric bypass or laparoscopic sleeve gastrectomy between 2015 and 2018 were included. Models used 5-fold cross-validation and were evaluated using the area under the receiver operating characteristic curve, the net reclassification index, and the integrated discrimination improvement., Results: The 30-day readmission rate among 393,833 patients was 3.9%. Super Learner area under the receiver operating characteristic curve was 0.674 (95% confidence interval 0.670-0.679), compared to 0.650 (95% confidence interval 0.645-0.654) for logistic regression. The net reclassification index was 0.239 (95% confidence interval 0.223-0.254), and 0.252 (95% confidence interval 0.249-0.255) for those who were and were not readmitted within 30 days. The integrated discrimination improvement was 0.0032 (95% confidence interval 0.0030-0.0033)., Conclusion: The Super Learner outperformed traditional logistic regression in predicting risk of 30-day readmission after bariatric surgery. Machine learning models may help target high-risk patients more optimally and prevent unnecessary readmissions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Treatment toxicities are common in older adults with cancer and consequently, treatment modifications are sometimes considered. We evaluated the prevalence and factors associated with treatment modifications at the first cycle in older patients receiving palliative systemic treatment., Methods: Patients (n = 369) from the GAP 70+ Trial (NCT02054741; PI: Mohile) usual care arm were included. Enrolled patients were aged 70+ with advanced cancer and ≥ 1 Geriatric Assessment (GA) domain impairment. Treatment modification was defined as any change from National Comprehensive Cancer Network guidelines or published clinical trials. Baseline variables included: 1) sociodemographic factors; 2) clinical variables; 3) GA domains; and 4) physician beliefs about life expectancy. Bivariate analyses and multivariable cluster-weighted generalized estimating equation model were conducted to assess the association of baseline variables with cycle 1 treatment modifications., Results: Mean age was 77.2 years (range: 70-94); 62% had lung or gastrointestinal cancers, and 35% had treatment modifications at cycle 1. Increasing age by one year (odds ratio (OR) 1.1, 95% confidence interval [CI] 1.0-1.2), receipt of ≥second line of chemotherapy (OR 1.8, CI 1.1-3.0), functional impairment (OR 1.6, CI 1.1-2.3) and income ≤$50,000 (OR 1.7, CI 1.1-2.4) were independently associated with a higher likelihood of cycle 1 treatment modification., Conclusion: Treatment modifications occurred in 35% of older adults with advanced cancer at cycle 1. Increasing age, receipt of ≥second line of chemotherapy, functional impairment, and lower income were independently associated with treatment modifications. These findings emphasize the need for evidence-based regimens in older adults with cancer and GA impairments., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Rural-urban disparities in the experiences of caregivers of older adults with advanced cancer may exist. This study examined factors associated with caregiver mastery and burden and explored whether rural-urban disparities in caregiver outcomes differed by education., Materials and Methods: Longitudinal data (baseline, 4-6 weeks, and 3 months) on caregivers of older adults (≥ 70) with advanced cancer were obtained from a multicenter geriatric assessment (GA) trial (ClinicalTrials.gov: NCT02107443). Rurality was determined based on 2010 Rural-Urban Commuting Area codes. Caregivers' education was categorized as ≥ some college vs ≤ high school. Caregiver outcomes included Ryff Environmental Mastery (scored 7-35) and Caregiver Reaction Assessment (including self-esteem, disrupted schedules, financial problems, lack of social support, and health problems; each scored 1-5). Separate linear mixed models with interaction term of education and rurality were performed., Results: Of 414 caregivers, 64 (15.5%) were from rural areas and 263 (63.5%) completed ≥ some college. Rurality was significantly associated with more disrupted schedules (β = 0.21), financial problems (β = 0.17), and lack of social support (β = 0.11). A significant interaction between education and rurality was found, with rurality associated with lower mastery (β = -1.27) and more disrupted schedule (β = 0.25), financial problems (β = 0.33), and lack of social support (β = 0.32) among caregivers with education ≤ high school., Conclusion: Our study identifies subgroups of caregivers who are vulnerable to caregiving burden, specifically those from rural areas and with lower education. Multifaceted interventions are needed to improve caregivers' competency and reduce caregiving burden., Competing Interests: Declaration of Competing Interest Dr. Kah Poh Loh serves as a consultant to Pfizer and Seattle Genetics. Dr. Allison Magnuson reports an honorarium for an educational lecture provided at the American Society of Radiation Oncology 2020 Annual meeting. All other authors have no relevant conflicts of interest to report., (Copyright © 2021 Elsevier Ltd. All rights reserved.)