bluuebunny/crossref_metadata_2025 huggingface dataset:
Interrogating two extensively self-targeting Type I CRISPR-Cas systems in Xanthomonas albilineans reveals distinct anti-CRISPR proteins that block DNA degradation
Authors: Wimmer Franziska , Englert Frank , Wandera Katharina G , Alkhnbashi Omer S , Collins Scott P , Backofen Rolf , Beisel Chase L
Published: November 2023

CRISPR-Cas systems store fragments of invader DNA as spacers to recognize and clear those same invaders in the future. Spacers can also be acquired from the host's genomic DNA, leading to lethal self-targeting. While self-targeting can be circumvented through different mechanisms, natural examples remain poorly explored. Here, we investigate extensive self-targeting by two CRISPR-Cas systems encoding 24 self-targeting spacers in the plant pathogen Xanthomonas albilineans. We show that the native I-C and I-F1 systems are actively expressed and that CRISPR RNAs are properly processed. When expressed in Escherichia coli, each Cascade complex binds its PAM-flanked DNA target to block transcription, while the addition of Cas3 paired with genome targeting induces cell killing. While exploring how X. albilineans survives self-targeting, we predicted putative anti-CRISPR proteins (Acrs) encoded within the bacterium's genome. Screening of identified candidates with cell-free transcription-translation systems and in E. coli revealed two Acrs, which we named AcrIC11 and AcrIF12Xal, that inhibit the activity of Cas3 but not Cascade of the respective system. While AcrF12Xal is homologous to AcrIF12, AcrIC11 shares sequence and structural homology with the anti-restriction protein KlcA. These findings help explain tolerance of self-targeting through two CRISPR-Cas systems and expand the known suite of DNA degradation-inhibiting Acrs.
Chromatin accessibility and pioneer factor FOXA1 restrict glucocorticoid receptor action in prostate cancer
Authors: Helminen Laura , Huttunen Jasmin , Tulonen Melina , Aaltonen Niina , Niskanen Einari A , Palvimo Jorma J , Paakinaho Ville
Published: November 2023

Treatment of prostate cancer relies predominantly on the inhibition of androgen receptor (AR) signaling. Despite the initial effectiveness of the antiandrogen therapies, the cancer often develops resistance to the AR blockade. One mechanism of the resistance is glucocorticoid receptor (GR)-mediated replacement of AR function. Nevertheless, the mechanistic ways and means how the GR-mediated antiandrogen resistance occurs have remained elusive. Here, we have discovered several crucial features of GR action in prostate cancer cells through genome-wide techniques. We detected that the replacement of AR by GR in enzalutamide-exposed prostate cancer cells occurs almost exclusively at pre-accessible chromatin sites displaying FOXA1 occupancy. Counterintuitively to the classical pioneer factor model, silencing of FOXA1 potentiated the chromatin binding and transcriptional activity of GR. This was attributed to FOXA1-mediated repression of the NR3C1 (gene encoding GR) expression via the corepressor TLE3. Moreover, the small-molecule inhibition of coactivator p300’s enzymatic activity efficiently restricted GR-mediated gene regulation and cell proliferation. Overall, we identified chromatin pre-accessibility and FOXA1-mediated repression as important regulators of GR action in prostate cancer, pointing out new avenues to oppose steroid receptor-mediated antiandrogen resistance.
Homeostatic iron regulatory protein drives glioblastoma growth via tumor cell-intrinsic and sex-specific responses
Authors: Troike Katie M , Wang Sabrina Z , Silver Daniel J , Lee Juyeun , Mulkearns-Hubert Erin E , Hajdari Nicole , Ghosh Prabar K , Kay Kristen E , Beilis Julia L , Mitchell Sofia E , Bishop Christopher W , Hong Ellen S , Artomov Mykyta , Hubert Christopher G , Rajappa Prajwal , Connor James R , Fox Paul L , Kristensen Bjarne W , Lathia Justin D
Published: November 2023

Background

Glioblastoma (GBM) displays alterations in iron that drive proliferation and tumor growth. Iron regulation is complex and involves many regulatory mechanisms, including the homeostatic iron regulator (HFE) gene, which encodes the homeostatic iron regulatory protein. While HFE is upregulated in GBM and correlates with poor survival outcomes, the function of HFE in GBM remains unclear.

Methods

We interrogated the impact of cell-intrinsic Hfe expression on proliferation and survival of intracranially implanted animals through genetic gain- and loss-of-function approaches in syngeneic mouse glioma models, along with in vivo immune assessments. We also determined the expression of iron-associated genes and their relationship to survival in GBM using public data sets and used transcriptional profiling to identify differentially expressed pathways in control compared to Hfe-knockdown cells.

Results

Overexpression of Hfe accelerated GBM proliferation and reduced animal survival, whereas suppression of Hfe induced apoptotic cell death and extended survival, which was more pronounced in females and associated with attenuation of natural killer cells and CD8+ T cell activity. Analysis of iron gene signatures in Hfe-knockdown cells revealed alterations in the expression of several iron-associated genes, suggesting global disruption of intracellular iron homeostasis. Further analysis of differentially expressed pathways revealed oxidative stress as the top pathway upregulated following Hfe loss. Hfe knockdown indeed resulted in enhanced 55Fe uptake and generation of reactive oxygen species.

Conclusions

These findings reveal an essential function for HFE in GBM cell growth and survival, as well as a sex-specific interaction with the immune response.
Blame avoidance and credit-claiming dynamics in government policy communications: evidence from leadership tweets in four OECD countries during the 2020–2022 COVID-19 pandemic
Authors: Leong Ching , Howlett Michael , Safaei Mehrdad
Published: November 2023

Government information activities are often thought to be motivated by a classic calculus of blame minimization and credit maximization. However, the precise interactions of “blame” and “credit” communication activities in government are not well understood, and questions abound about how they are deployed in practice. This paper uses Natural Language Processing (NLP) machine-learning sentiment analysis of a unique dataset composed of several thousand tweets of high-level political leaders in four OECD countries—namely the Prime Ministers of the United Kingdom, Ireland, Australia, and Canada—during 2020–2022 to examine the relationships existing between “blame” and “credit” communication strategies and their relation to the changing severity of the COVID-19 pandemic, both in an objective and subjective sense. In general, the study suggests that during this high-impact, long-lasting, and waxing and waning crisis, political leaders acted in accordance with theoretical expectations when it came to communicating credit seeking messages during the periods when the COVID situation was thought to be improving, but they did not exclusively rely upon communicating blame or scapegoating when the situation was considered to be deteriorating. The consequences of this finding for blame and credit-based theories of government communication are then discussed.
Effects of Respiratory Muscle Training on Exercise Capacity, Quality of Life, and Respiratory and Pulmonary Function in People With Ischemic Heart Disease: Systematic Review and Meta-Analysis
Authors: Fabero-Garrido Raúl , del Corral Tamara , Plaza-Manzano Gustavo , Sanz-Ayan Paz , Izquierdo-García Juan , López-de-Uralde-Villanueva Ibai
Published: November 2023

Objective

This systematic review and meta-analysis aimed to evaluate the effects of respiratory muscle training (RMT) on functional exercise capacity, health-related quality of life (HRQoL), respiratory muscle function, and pulmonary function in individuals with ischemic heart disease (IHD).

Methods

The MEDLINE, Web of Science, Scopus, PEDro, CINAHL, Science Direct, and CENTRAL electronic databases were searched in January 2023. Randomized controlled trials published in English, Spanish, or Portuguese that were conducted to determine the effect of RMT versus passive control and/or sham RMT on the target variables in individuals with IHD, irrespective of age or sex were included. Two reviewers performed the searches and extraction of the most relevant data. The quality and risk of bias for each included study were examined with the PEDro scale and Cochrane risk-of-bias tool.

Results

Thirteen studies (849 participants) were included. The meta-analysis showed a significant increase in peak oxygen consumption (mean difference [MD] = 2.18 mL·kg−1·min−1 [95% CI = 0.54 to 3.83]), inspiratory muscle strength (MD = 16.62 cm H2O [95% CI = 12.48 to 20.77]), inspiratory muscle endurance (standardized mean difference = 0.39 [95% CI = 0.19 to 0.60]), and expiratory muscle strength (MD = 14.52 cm H2O [95% CI = 5.51 to 23.53]). There were no benefits in 6-minute walking distance (MD = 37.57 m [95% CI = −36.34 to 111.48]), HRQoL (standardized mean difference = 0.22 [95% CI = −0.16 to 0.60]), pulmonary function (forced vital capacity; MD = 2.07% of predicted value [95% CI = −0.90 to 5.03], or forced expiratory volume at the first second (MD = −0.75% of predicted value [95% CI = −5.45 to 3.95]).

Conclusion

This meta-analysis provided high- and moderate-quality evidence that inspiratory muscle training (IMT) improves inspiratory muscle strength and endurance, respectively; and very low-quality evidence for effects on peak oxygen consumption and expiratory muscle strength in individuals with IHD. No superior effects were found in the 6-minute walking test, HRQoL, or pulmonary function compared with the control group.

Impact

The results shown in this systematic review with meta-analysis will provide clinicians a better understanding of the effects of IMT in people with IHD. IMT could be integrated into the cardiac rehabilitation management, although more research is needed.
Mental health, quality of life and self-management behaviours: online evaluation of inflammatory arthritis patients over 1 year of COVID-19 lockdowns
Authors: Sweeney Melissa , Carpenter Lewis , de Souza Savia , Chaplin Hema , Tung Hsiu , Caton Emma , Galloway James , Cope Andrew , Yates Mark , Nikiphorou Elena , Norton Sam
Published: November 2023

Objective

Patients with inflammatory arthritis were especially vulnerable to the psychosocial and health impacts of coronavirus disease 2019 (COVID-19) and the lockdowns. This study investigated the impact of these changes on mental health, physical health and quality of life for inflammatory arthritis patients over 1 year following the initial lockdown in the UK.

Methods

Three hundred and thirty-eight participants with inflammatory arthritis completed an ambidirectional study consisting of online questionnaires at four time points for 1 year. The questionnaires assessed demographic information, inflammatory arthritis condition, mental health, physical symptoms, self-management behaviours, COVID-19 status and impacts. Means, linear regressions and structural equation modelling for mediations were conducted over 12 months.

Results

Physical health concerns peaked during June 2020, then declined, but did not return to baseline. Depression was associated with worse quality of life at baseline, as shown by the beta coefficient, (β= 0.94, P < 0.01), September (β = 0.92, P < 0.01), November (β= 0.77, P < 0.01) and 1 year (β = 0.77, P < 0.01). Likewise, anxiety was associated with worse quality of life at baseline (β = 1.92, P < 0.01), September (β = 2.06, P < 0.01), November (β = 1.66, P = 0.03) and 1 year (β = 1.51, P = 0.02). The association between depression and quality of life was mediated by physical activity (β= 0.13, P < 0.01) at baseline. The association between anxiety and quality of life was also mediated by physical activity (β = 0.25, P = 0.04) at baseline.

Conclusion

Physical health continued to be worse 1 year later compared with before the COVID-19 lockdowns in patients with inflammatory arthritis. Mental health showed long-term effects on quality of life, with an impact for ≥12 months. Lastly, physical activity mediated between mental health and quality of life in the short term.
Ethnopharmacology and phytochemistry of medicinal plants against enterocyte bacteria-linked infections and diarrhoea in some African countries: a systematic review
Authors: Onohuean Hope , Igere Bright E
Published: November 2023

Background

There is a dearth of relevant bioactive translational progress and post-scientific evidence on the ethnopharmacology and phytochemistry of plants with anti-diarrheal potential in Africa. This study synthesized scientific evidence on commonly used African folkloric medicinal plants in the management/control of diarrhoea and antibiotic-resistant enterocyte-infecting bacteria in some African countries.

Main body

Published articles from different databases on folk medicinal plants used in the treatment/management of bacteria-linked enterocyte infections and diarrhoea were reviewed systematically. The ethnopharmacology and phytochemistry of 75 folkloric plant species belonging to 67 families and 58 genera, including Asteraceae (10.45%), Myrtaceae (7.46%), (Anacardiaceae, Celastraceae, Fabaceae and Hydnoraceae) (5.97%) are the most used anti-diarrheal folkloric plants in the region. The minimum inhibitory concentration (MIC) (0.018 mg/ml–8.45 mg/ml) or (39 μg/ml–2000 μg/ml) and 14.35 g/kg–8317.64 mg/kg LD50 on enterocyte bacteria strains. A solo author reported MIC of the pure component 6.25 μg/ml. Tree (38%) and tuber (3%) were the highest and least life forms of the folkloric plants used. Leaves (41%) were the most frequently used for folk preparations, while aerial, fruits, seeds and combination of shoots + leaves (1.45%) were the least used. Fourteen authors’ studies revealed the phytochemical profile, while six further elucidated the bioactive components of the folkloric plants used to manage diarrhoea.

Conclusion

Our findings revealed the antibacterial potency of folkloric plants against diarrhoea and multiple antibiotic-resistant organisms. It suggests a gap in the appropriate documentation, application of such medicinal/folkloric plants, and low post-research advancement of effectively tested plant types or bioactive agents, calling for well-organized future research engagements.
Disclosure in Civil Proceedings in the UK and Kazakhstan: Comparative Analysis
Authors: Satayeva Aizhan
Published: November 2023

The relevance of the chosen problem is conditioned by the need to develop theoretical ideas about the institution of disclosure of documents in the civil procedural legislation of the Republic of Kazakhstan, considering the experience of the UK, which will emphasize the potential of this measure to improve procedural discipline and ensure legal certainty in making court decisions and increase the level of legal culture in Kazakhstan, which may affect the effectiveness of this procedure or this institution in practice. The purpose of this study was to characterize the institute of disclosure of documents in civil proceedings using methods of comparative legal analysis of English contract law and the current legislation of the Republic of Kazakhstan. The methodological basis of the study consists of dialectical method, comparative legal analysis, analysis and synthesis, formal and logical, formal and legal, classification and grouping, and questionnaire methods. There is an urgent need to develop theoretical ideas about the disclosure of documents in the Republic of Kazakhstan, especially in light of the introduction of new elements of disclosure such as pre-trial protocol in the civil process.
The state of knowledge regarding delivering behavior change techniques via short text messages is already quite advanced: A response to “Can behavior change techniques be delivered via short text messages?”
Authors: Correia Simao Sara , Bartlett Yvonne Kiera , French David P
Published: November 2023

Doğru et al. recent study reported developing text messages that attempted to capture each of 93 behavior change techniques (BCTs) in a standardized taxonomy. They found that a panel of experts identified the majority of the messages developed as having good fidelity to the intended BCTs. While this work has clear merit, we do not believe it accurately reflects the large body of existing research in this area. A process of producing text messages to address BCTs that yielded high fidelity has previously been reported. Furthermore, this work showed that messages developed for one behavior can be modified to address another behavior with similarly good fidelity. Importantly, these messages have been shown to successfully change target constructs in an experimental study and are being used in a randomized trial that has recently completed recruitment of over 1000 people with Type 2 diabetes.
A network-based transcriptomic landscape of HepG2 cells uncovering causal gene-cytotoxicity interactions underlying drug-induced liver injury
Authors: Wijaya Lukas S , Gabor Attila , Pot Iris E , van de Have Luca , Saez-Rodriguez Julio , Stevens James L , Le Dévédec Sylvia E , Callegaro Giulia , van de Water Bob
Published: November 2023

Drug-induced liver injury (DILI) remains the main reason for drug development attritions largely due to poor mechanistic understanding. Toxicogenomic to interrogate the mechanism of DILI has been broadly performed. Gene coregulation network-based transcriptome analysis is a bioinformatics approach that potentially contributes to improve mechanistic interpretation of toxicogenomic data. Here we performed an extensive concentration time course response-toxicogenomic study in the HepG2 cell line exposed to 20 DILI compounds, 7 reference compounds for stress response pathways, and 10 agonists for cytokines and growth factor receptors. We performed whole transcriptome targeted RNA sequencing to more than 500 conditions and applied weighted gene coregulated network analysis to the transcriptomics data followed by the identification of gene coregulated networks (modules) that were strongly modulated upon the exposure of DILI compounds. Preservation analysis on the module responses of HepG2 and PHH demonstrated highly preserved adaptive stress response gene coregulated networks. We correlated gene coregulated networks with cell death onset and causal relationships of 67 critical target genes of these modules with the onset of cell death was evaluated using RNA interference screening. We identified GTPBP2, HSPA1B, IRF1, SIRT1, and TSC22D3 as essential modulators of DILI compound-induced cell death. These genes were also induced by DILI compounds in PHH. Altogether, we demonstrate the application of large transcriptome datasets combined with network-based analysis and biological validation to uncover the candidate determinants of DILI.
Evolutionary game analysis of shared parking market diffusion under government management
Authors: Wei Qingqi , Xiao Guomei
Published: November 2023

The imbalance between supply and demand in urban settings poses a significant barrier to the sustainable advancement of urban transportation. Shared parking serves as a viable solution to mitigate these challenges. Nevertheless, for its sustained growth, a regulatory mechanism enforced by the government is imperative. To promote shared parking market diffusion, we construct an evolutionary game model that incorporates the government, enterprises and parking demanders. It explores stabilization strategies for these stakeholders and identifies multiple equilibrium states under different parameter conditions. The results show that the rate and stability of these evolutionary strategies are constrained by the mutual benefits derived by the three parties. Furthermore, such stakeholders are reciprocally influenced by their willingness to engage in shared parking to varying degrees. Government subsidies serve as a determining factor for the strategic choices made by both enterprises and demanders, albeit at different evolutionary rates. Demanders who have a higher value of time tend to park on-street, thereby influencing enterprise strategies. To foster the long-term growth of the shared parking market, the government must enact appropriate subsidy policies, maintain consistent regulations and advocate for increased subsidies for parking demanders to reduce the effect of temporal heterogeneity on parking behavioural choices.
Mechanical loading intensities affect the release of extracellular vesicles from mouse bone marrow‐derived hematopoietic progenitor cells and change their osteoclast‐modulating effect
Authors: Bratengeier C. , Johansson L. , Liszka A. , Bakker A. D. , Hallbeck M. , Fahlgren A.
Published: November 2023

Low‐intensity loading maintains or increases bone mass, whereas lack of mechanical loading and high‐intensity loading decreases bone mass, possibly via the release of extracellular vesicles by mechanosensitive bone cells. How different loading intensities alter the biological effect of these vesicles is not fully understood. Dynamic fluid shear stress at low intensity (0.7 ± 0.3 Pa, 5 Hz) or high intensity (2.9 ± 0.2 Pa, 1 Hz) was used on mouse hematopoietic progenitor cells for 2 min in the presence or absence of chemical compounds that inhibit release or biogenesis of extracellular vesicles. We used a Receptor activator of nuclear factor kappa‐Β ligand‐induced osteoclastogenesis assay to evaluate the biological effect of different fractions of extracellular vesicles obtained through centrifugation of medium from hematopoietic stem cells. Osteoclast formation was reduced by microvesicles (10 000× g) obtained after low‐intensity loading and induced by exosomes (100 000× g) obtained after high‐intensity loading. These osteoclast‐modulating effects could be diminished or eliminated by depletion of extracellular vesicles from the conditioned medium, inhibition of general extracellular vesicle release, inhibition of microvesicle biogenesis (low intensity), inhibition of ESCRT‐independent exosome biogenesis (high intensity), as well as by inhibition of dynamin‐dependent vesicle uptake in osteoclast progenitor cells. Taken together, the intensity of mechanical loading affects the release of extracellular vesicles and change their osteoclast‐modulating effect.
Nonobstetric Surgery and Later Childhood Development: Optimal Anesthesia for the Mother-infant Dyad
Authors: Kearns R.J. , Shaw M. , Nelson S.M.
Published: November 2023

(Anaesthesia. 2023;78:143–146)

While nonobstetric surgery during pregnancy is uncommon (<1%), it can be a serious cause for concern for mother and baby. In 2016, the American Food and Drug Administration cautioned that general anesthesia (GA) use during the third trimester of pregnancy may increase the risk of impaired neurodevelopment in children of mothers exposed. A later randomized trial found no association between short-duration general anesthesia and increased risk of childhood neurodevelopment issues. Given the vulnerable nature of fetuses in utero, the topic of anesthesia use during pregnancy and its impact on children remains a topic of interest and importance.
Preparing for Obstetric Anaesthesia-An Educational Randomized Controlled Trial Comparing E-learning to Written Course Material
Authors: Andersson M.L. , Duch P. , Bessmann E.L. , Lundstrøm L.H. , Ekelund K.
Published: November 2023

(Acta Anaesthesiol Scand. 2023;67:36–43)

E-learning is becoming more common in postgraduate continual medical education. While many studies have shown the benefits of e-learning and its effectiveness is similar to traditional teaching methods, the studies vary in quality. This study aimed to determine whether e-learning better prepares obstetric anesthesia course participants compared to written course material by assessing precourse knowledge, anxiety level, group performance, and postcourse knowledge.
Maternal Cardiovascular Morbidity Events Following Preeclampsia: A Retrospective Cohort Study
Authors: Meng M.L. , Frere Z. , Fuller M. , Li Y.J. , Habib A.S. , Federspiel J.J. , Wheeler S.M. , Gilner J.B. , Shah S.H. , Ohnuma T. , Raghunathan K. , Krishnamoorthy V.
Published: November 2023

(Anesth Analg. 2023;136:728–737)

It has been shown that cardiovascular disease is related to preeclampsia. It has also been found that preeclampsia can increase the risk of heart failure, maternal mortality, and other cardiovascular conditions. This study aimed to show the relationship between cardiovascular diseases and preeclampsia in patients.
Comparison of Different Delivery Modalities of Epidural Analgesia and Intravenous Analgesia in Labor: A Systematic Review and Network Meta-analysis
Authors: Wydall S. , Zolger D. , Owolabi A. , Nzekwu B. , Onwochei D. , Desai N.
Published: November 2023

(Can J Anesth/J Can Anesth. 2023;70:406–442)

There is still no preferred method of delivering neuraxial analgesia to pregnant patients. There are options such as continuous epidural infusion (CEI) and intermittent epidural bolus which can be controlled by a machine (programmed intermittent epidural bolus—PIEB), demand from an anesthesia provider (demand intermittent epidural bolus—DIEB), or the patient themselves (patient-controlled epidural analgesia—PCEA). The use of opioids for labor analgesia is also common in those who cannot receive spinal analgesia. This study aimed to compare the relationship between different analgesia delivery methods on maternal, fetal, and neonatal outcomes.
Manually Controlled, Continuous Infusion of Phenylephrine or Norepinephrine for Maintenance of Blood Pressure and Cardiac Output During Spinal Anesthesia for Cesarean Delivery: A Double-Blinded Randomized Study
Authors: Belin O. , Casteres C. , Alouini S. , Le Pape M. , Dupont A. , Boulain T.
Published: November 2023

(Anesth Analg. 2023;136:540–550)

Spinal anesthesia (SA) can induce maternal hypotension which may compromise uteroplacental and fetal perfusion. Current practices that counteract SA-induced vasodilation employ a phenylephrine or norepinephrine infusion through computer-controlled, fixed-rate, and manual delivery methods. The current study investigated the hemodynamic effects of continuous infusion of norepinephrine compared with phenylephrine in maintaining cardiac index (CI) during cesarean delivery (CD) under SA.
Successful Surgical Cricothyroidotomy Following an Obstetric “Can’t Oxygenate” Scenario: A Narrative of Enabling Factors
Authors: Hill J.S. , Robinson E.
Published: November 2023

(Int J Obstet Anesth. 2023;53:103611)

This report involves a case of failed intubation during general anesthesia (GA) during cesarean delivery (CD) followed by a successful surgical cricothyroidotomy and discusses technical and nontechnical factors. A 40 y/o, G3P1 at 28+3 weeks of gestation with blood pressure of 150/100 mm Hg was diagnosed with pre-eclampsia and admitted to the hospital. At 29+0 weeks gestation, the patient reported chest and abdominal pain. Blood pressure readings were 200/120 mm Hg. The patient received oral labetalol, intravenous magnesium, and oral nifedipine. Blood pressure dropped to 146/78 mm Hg, and labs showed normal platelet count and hemoglobin concentration yet slightly elevated alanine aminotransferase and alkaline phosphatase. Five hours later, when a CD was done for fetal indications, the patient’s platelet count was 50×109/L, so the CD was performed under GA.
Altered profiles of circulating cytokines in chronic liver diseases (NAFLD/HCC): Impact of the PNPLA3 I148M risk allele
Authors: Kirchmeyer Mélanie , Gaigneaux Anthoula , Servais Florence A. , Arslanow Anita , Casper Markus , Krawczyk Marcin , Lammert Frank , Behrmann Iris
Published: November 2023

Background:

Individuals carrying the risk variant p.I148M of patatin-like phospholipase domain-containing protein 3 (PNPLA3) have a higher susceptibility to fatty liver diseases and associated complications, including HCC, a cancer closely linked to chronic inflammation. Here, we assessed circulating cytokine profiles for patients with chronic liver diseases genotyped for PNPLA3.

Methods:

Serum concentrations of 22 cytokines were measured by multiplex sandwich-ELISA. The cohort comprised 123 individuals: 67 patients with NAFLD without cirrhosis (57 steatosis, 10 NASH), 24 patients with NAFLD with cirrhosis, 21 patients with HCC (15 cirrhosis), and 11 healthy controls. Receiver operator characteristic analyses were performed to assess the suitability of the cytokine profiles for the prediction of steatosis, cirrhosis, and HCC.

Results:

HGF, IL-6, and IL-8 levels were increased in patients, with ∼2-fold higher levels in patients with cirrhosis versus healthy, while platelet derived growth factor-BB (PDGF-BB) and regulated on activation, normal T cell expressed and secreted (RANTES) showed lower concentrations compared to controls. Migration inhibitory factor and monocyte chemoattractant protein-1 (MCP-1) were found at higher levels in NAFLD samples (maximum: NAFLD-cirrhosis) versus healthy controls and HCC samples. In receiver operator characteristic analyses, migration inhibitory factor, IL-8, IL-6, and monocyte chemoattractant protein-1 yielded high sensitivity scores for predicting noncirrhotic NAFLD (vs. healthy). The top combination to predict cirrhosis was HGF plus PDGF-BB. Migration inhibitory factor performed best to discriminate HCC from NAFLD; the addition of monokine induced gamma (MIG), RANTES, IL-4, macrophage colony-stimulating factor (M-CSF), or IL-17A as second parameters further increased the AUC values (> 0.9). No significant impact of the PNPLA3

I148M
allele on cytokine levels was observed in this cohort.

Conclusions:

Cytokines have biomarker potential in patients with fatty liver, possibly suited for early HCC detection in patients with fatty liver. Patients carrying the PNPLA3 risk allele did not present significantly different levels of circulating cytokines.
Hypoxia-inducible factor-prolyl hydroxylase inhibitor Roxadustat (FG-4592) reduces renal fibrosis in Dahl salt-sensitive rats
Authors: Naito Yoshiro , Yasumura Seiki , Okuno Keisuke , Asakura Masanori , Tsujino Takeshi , Masuyama Tohru , Ishihara Masaharu
Published: November 2023

Objective:

Although hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors have been developed for the treatment of renal anemia, their effects on cardiac and renal dysfunction remain unknown. We previously reported on Dahl salt-sensitive rats, in a rat model of salt-sensitive hypertension, that exhibited anemia and impaired expression of duodenal iron transporters after the development of hypertensive cardiac and renal dysfunction. Therefore, we investigated the effects of Roxadustat (FG-4592), an HIF-PH inhibitor, on anemia, iron regulation, and cardiac and renal dysfunction in Dahl salt-sensitive rats.

Methods:

Six-week-old male Dahl salt-sensitive rats were fed a normal or high-salt diet for 8 weeks. A further subset of Dahl salt-sensitive rats, that were fed a high-salt diet, was administered Roxadustat for 8 weeks.

Results:

Dahl salt-sensitive rats fed a high-salt diet developed hypertension, cardiac and renal dysfunction, and anemia after 8 weeks of feeding. Roxadustat increased hemoglobin and serum erythropoietin levels in Dahl salt-sensitive rats fed a high-salt diet. With regard to the iron-regulating system, Roxadustat lowered hepatic hepcidin gene expression and increased the gene expression of duodenal iron transporters, such as cytochrome b and divalent metal transporter 1, in Dahl salt-sensitive rats fed a high-salt diet. Roxadustat did not affect the development of hypertension and cardiac hypertrophy in Dahl salt-sensitive rats with a high-salt diet; however, Roxadustat treatment attenuated renal fibrosis in these rats.

Conclusions:

Roxadustat ameliorated anemia with affecting the gene expression of the iron-regulating system, and did not affect cardiac hypertrophy but attenuated renal fibrosis in Dahl salt-sensitive rats fed a high-salt diet.
Improving Nurses' Attitudes Toward Substance Use Disorder
Authors: Manzotti Ashley , Avery-Desmarais Shannon , Ducharme Maria , Elliott Kathleen , Misto Kara
Published: November 2023

Patients with substance use disorder (SUD) encounter many barriers to healthcare, including negative attitudes of healthcare personnel. Compared with other healthcare professions, nurses have been reported as having less tolerant attitudes toward patients with SUD. Knowledge acquisition combined with role support has been shown to improve therapeutic attitudes of nurses toward patients with SUD. Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based educational intervention aimed to improve the outcomes of patients at risk and with SUD. SBIRT education has been shown as an effective educational tool with licensed nurses. Therefore, the aim of this study was to evaluate whether a 2-hour educational session on SBIRT (Mitchell et al., 2013) improved the therapeutic attitudes of nurses toward patients with SUD. Peplau's theory of interpersonal relations guided this study with an emphasis on the nurse–patient relationship. A quasi-experimental pretest/posttest design was used to evaluate nurses' attitudes pre and post a 2-hour educational session. Participants included 65 registered nurses employed in a 247-bed teaching hospital in New England. Attitudes were measured before and after the educational session using the 20-item, five-subscale Drug and Drug Problems Perceptions Questionnaire. A paired t test was performed, showing statistically significant improvements in attitudes postintervention. Prior education on SUD significantly correlated with baseline attitudes. A standard regression model, with practice setting, family history of SUD, and prior education as dependent variables, was not predictive of baseline attitudes. The results suggest conducting SBIRT should be considered a mandatory nursing competency, both in undergraduate curriculum and among licensed nurses.
Enhancing Knowledge and Attitudes Regarding Opioid Use Disorder Among Private Primary Care Clinics
Authors: Jassar Sukhwant Kaur , Hundley Amanda , Giesler Amanda
Published: November 2023

Opioid use disorder (OUD) continues to impact communities worldwide. British Columbia specifically declared a public health emergency in April 2016. It is known that patients with OUD often experience barriers in access to care, including limited knowledge and training among providers, as well as persisting stigma in the medical community. The Doctor of Nursing Practice quality improvement project sought to provide barrier-targeted OUD education while using multiple effective teaching methods, such as test-enhanced learning, to family nurse practitioners (FNPs) working among private primary care clinics to assess the impact on knowledge and attitudes. In review of an experience survey, zero participants had received prior education on OUD (N = 7). The Drug and Drug Problems Perceptions Questionnaire was used to assess attitudes. In review of the data, attitudes before receiving education (Mdn = 74) improved after receiving barrier-targeted education (Mdn = 66), W = 0, p < .05. Knowledge was tested at three time points. After a review of unique identifiers, four participant tests were successfully linked. It was found that knowledge after receiving education (M = 7.75, Mdn = 7.5) improved in comparison with baseline knowledge (M = 6, Mdn = 6) and further improved after a 1-month time frame (M = 8.5, Mdn = 8.5). Although the project was limited by sample size, providing education to FNPs who have not received prior education on OUD, and using modalities such as test-enhanced learning, showed a favorable impact on knowledge and attitudes. In light of the opioid epidemic, nursing leaders must continue to actively engage practicing FNPs and students with OUD education. FNPs are well positioned to be champions in this area and may mobilize teams to overcome barriers among private primary care clinics and increase access to care.
Is the Clinical Practicum in Addiction Treatment Facilities an Effective Educational Intervention to Improve Nursing Students' Attitudes Toward Alcohol Use Disorders?
Authors: de Vargas Divane
Published: November 2023

The paucity of education and training on alcohol use disorders (AUDs) in nursing curricula is the main predictor of negative attitudes and results in limited knowledge access and delivery of health care for persons experiencing these problems. Although experts advocate increasing the time devoted to alcohol-related content in a crowded curriculum, didactic strategies for teaching about addiction in prequalifying nursing education have been discussed. This study aimed to verify the effectiveness of an educational experience that integrated clinical practicum experience in addiction treatment facilities for nursing students' attitudes. A quasi-experimental one-group study with pre-and-post 3-month follow-ups was carried out with 108 nursing students who answered the Attitudes Scale toward Alcohol, Alcohol Use Disorder, and Patients with Alcohol Use Disorders. The effect of the clinical practicum was apparent, with statistically significant changes to more positive global attitude scores in all measures. Previous educational intervention for AUDs during nursing education was a predictor of positive attitudes (OR = 7.21, p < .04). Students' self-perceived skills and professional preparation to deliver and direct care for patients with AUDs improved after the intervention, suggesting that clinical practice influenced students' skills for AUD identification across nursing practice. Previous contact with this population with lack of training in substance use disorder seems to favor negative attitude development. Clinical practicum experience in addiction treatment facilities improved nursing students' attitudes toward AUDs and patients with AUDs, and its effects were sustained 3 months later.
Associations of Psychological Distress and Alcohol Use Patterns Among Older Adults of Sexual Minority Status and Heterosexual Peers
Authors: Tran Carolyn K. , Casarez Rebecca L. , Nash Angela J. , Wilkerson J. Michael , Cron Stanley
Published: November 2023

Background

There is limited research investigating sexual-orientation-related differences in older adults and their relationship with alcohol use.

Objective

The purpose of this study was to determine if sexual minority status moderates the relationship between psychological distress and alcohol drinking patterns.

Methods

This study was a secondary analysis of data from the 2017–2018 National Survey on Drug Use and Health. Health outcomes among lesbian, gay, and bisexual (LGB) older adults (N = 462) aged 50 years or older were compared with heterosexual (N = 16,856) peers using univariate analyses and logistic regressions. Interaction terms evaluated the influence of sexual orientation on psychological distress and alcohol consumption.

Results

Sexual orientation was a predictor of alcohol use in the past year, past month, and at any time (p < .001) but was not a predictor of alcohol dependence or misuse, binge drinking, or heavy drinking. Heterosexual older adults were less likely to consume alcohol than those who identified as LGB. Respondents not reporting psychological distress were less likely to engage in problematic drinking. However, there was no evidence that sexual minority status moderates the relationship between psychological distress and alcohol use.

Conclusion

Limited evidence supports higher rates of alcohol use and alcohol-related problems among sexual minority persons than heterosexuals. Prediction models for alcohol use were not improved by using sexual orientation and psychological distress as interaction terms. Future research should examine the underlying causes of impaired health in the older LGB population. Those findings should be used to research methods of preventing and minimizing alcohol misuse.
Effect of COVID-19 Risk Perception and COVID-19 Self-Care of Korean Correctional Nurses on Occupational Burnout: Mediating Effect of Stress and Anxiety About Viral Epidemics
Authors: Jung Hyun-Ok , Han Seung-Woo
Published: November 2023

The purpose of this study was to investigate whether stress and anxiety about viral epidemics have effects as parameters in the relationship among COVID-19 risk perception, COVID-19 self-care, and occupational burnout for Korean correctional nurses. The subjects of this study were 107 correctional nurses working at 52 correctional facilities in Korea that are conducting COVID-19 management and prevention activities. Data were collected from March 12 to 30, 2022. Results suggest that correctional nurses during the COVID-19 pandemic may experience occupational burnout because of increased stress and anxiety about viral epidemics as their COVID-19 risk perception increased. In addition, stress and anxiety about being infected with the COVID-19 virus itself will cause burnout. This study contributes to promotion of the mental health of Korean correctional nurses and provides basic data for developing an intervention program to prevent occupational burnout.
Advancing a Comprehensive Multilevel Approach to Sexual Violence Prevention Using Existing Efficacious Programs
Authors: Schipani-McLaughlin Anne Marie , Gilmore Amanda K. , Salazar Laura F. , Potter Sharyn J. , Stapleton Jane G. , Orchowski Lindsay M.
Published: November 2023

Sexual violence (SV) is a serious and long-standing public health problem on college campuses. At institutions of higher education, campus administrators, activists, and practitioners have worked for decades to address campus SV. Despite federally mandated campus SV prevention programming, rates of campus SV remain unchanged. The purpose of this commentary is to outline a strategy for enhancing campus SV prevention efforts using a comprehensive multilevel approach utilizing existing efficacious programs. The following three strategies for implementing optimal campus SV prevention are proposed, which include (a) the need to prioritize efficacy, (b) targeting multiple levels of the social ecology, and (c) leveraging the benefits of in-person programming and technology-driven prevention. A call to action is included for both institutions of higher education administrators and practitioners to implement and invest in comprehensive multilevel interventions using existing, efficacious SV programs, ideally combining a technology-based program with an in-person component. Furthermore, a coordinated effort between prevention and response is needed to achieve successful prevention of campus SV and revictimization, including a connection with the community for postassault interventions. Thus, implementing multilevel interventions on college campuses using existing evidence-based programs in combination with a coordinated community response of postassault interventions can bring the campus community together and is optimal to moving the needle on rates of campus SV.
Quality of Nursing Care Perceived by People With HIV in Brazil: A Cross-Sectional Study
Authors: Santos Adriano Maia dos , Magno Laio , Anjos Eduarda Ferreira dos , Porto Jessica Prates , Barroso Rosemary Rocha Fonseca , Araújo Maria da Purificação Nazaré , Guimarães Bárbara Emanuely de Brito , Prado Nília Maria Brito Lima
Published: November 2023

We evaluated the quality of care provided by the nursing team within specialized care services (SCS) from the perspective of persons with HIV (PWH). A cross-sectional study was conducted in 25 SCS selected by a single-stage cluster sampling in 21 municipalities in Brazil. Systematic sampling was performed between October 2019 and March 2020 in the reception areas of SCS locations to choose the study population (N = 377). The adapted and validated Quality of Care Through the Patient's Eyes-HIV (QUOTE-HIV) questionnaire was used to measure the quality of perceived care, and the Mann–Whitney test to compare the scores between men and women. Of the 377 PWH, most were women (57.71%), Black or Brown (85.9%), heterosexual (67.1%), and cisgendered (96.0%); the mean age was ≥30 years (76.1%). Users' evaluation of the care provided by SCS according to scores of importance and performance of the QUOTE-HIV instrument ranged from 5.60 to 8.95 and 0.03 to 0.76, respectively. The perception of PWH about the quality of care provided by the nursing team in SCS suggests that there are opportunities to improve.
Experiences of Family Caregivers Providing Home Care to Older Patients With Cancer: A Qualitative Study
Authors: YANG Cheng-Fang , TSENG Chien-Ning , LIAO Yuan-Ju , GAO Zi-Xuan , CHEN Hsiao-Ping , CHANG Po-Chih , LEE Yun-Hsiang
Published: November 2023

Background

Older patients with cancer receive anticancer therapy in outpatient settings, and care-related issues may occur after discharge, which often requires family caregivers (FCs) to play a significant role in providing cancer care at home. However, relatively few studies have been focused on exploring the care experiences of these FCs.

Purpose

The aim of this study was to explore the care experiences of FCs caring for older family members with cancer at home.

Methods

A qualitative study design and in-depth individual interviews were used to explore the at-home care experiences of FCs of older patients with cancer. The research was conducted in chemotherapy outpatient settings of a medical center in northern Taiwan. Content analysis was used to analyze data. The analyses focused on first extracting meaningful units from the text and then inducting categories from these units and determining the major themes.

Results

Twenty FCs were interviewed. The three themes identified included (a) increased information needs and challenges in diet preparation and treatment decision making, (b) personal and patient-induced emotional stress, and (c) life rebalancing through the care experience.

Conclusions/Implications for Practice

The findings highlight the educational requirements, especially related to meeting personal dietary needs and obtaining psychological support, for FCs caring for older patients with cancer to help them rebalance their life.
Identification of the consistently differential expressed hub mRNAs and proteins in lung adenocarcinoma and contraction of the prognostic signature: a multidimensional analysis
Authors: Liu Yiran , Li Zhenyu , Meng Qianyao , Ning Anhui , Zhou Shenxuan , Li Siqi , Tao Xiaobo , Wu Yutong , Chen Qiong , Tian Tian , Zhang Lei , Cui Jiahua , Mao Liping , Chu Minjie
Published: November 2023

Background:

This study aimed to elucidate the consistency of differentially expressed hub mRNAs and proteins in lung adenocarcinoma (LUAD) across populations and to construct a comprehensive LUAD prognostic signature.

Methods:

The transcriptomic and proteomics data from different populations were standardized and analyzed using the same criteria to identify the consistently differential expressed mRNAs and proteins across genders and races. We then integrated prognosis-related mRNAs with clinical, pathological and EGFR mutation data to construct a survival model, subsequently validating it across populations. Through plasma proteomics, plasma proteins that consistently differential expressed with LUAD tissues were screened and validated, with their associations discerned by measuring expressions in tumor tissues and tumor vascular normalization.

Results:

The consistency rate of differentially expressed mRNAs and proteins was approximately 20%- 40%, with ethnic factors leading to about 40% consistency of differential expressed mRNA or protein across populations. The survival model based on the identified 8 hub mRNAs as well as stage, smoking status, and EGFR mutations demonstrated good prognostic prediction capabilities in both Western and East Asian populations, with a higher number of unfavorable variables indicating poorer LUAD prognosis. Notably, GPI expression in tumor tissues was inversely correlated with vascular normalization and positively correlated with plasma GPI expression.

Conclusion:

Our study underscores the significance of integrating transcriptomics and proteomics data, emphasizing the need to account for genetic diversity among ethnic groups. The developed survival model may offer a holistic perspective on LUAD progression, enhancing prognosis and therapeutic strategies.