bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient preferences of patient selection criteria for upper extremity vascularized composite allotransplantation: A qualitative study
Authors: Vanterpool Karen B. , Gacki-Smith Jessica , Downey Max C. , Nordstrom Michelle , Luken Michelle , Riggleman Tiffany , Fichter Shannon , Altema Withney , Jensen Sally E. , Dumanian Gregory A. , Cooney Carisa M. , Levan Macey L. , Tintle Scott , Brandacher Gerald , Gordon Elisa J.
Published: June 2023

Background:

Upper extremity vascularized composite allotransplantation is a life-enhancing reconstructive treatment option that aims to improve recipients’ quality of life and maximize function. This study assessed upper extremity vascularized composite allotransplantation patient selection criteria perceptions among individuals with upper extremity limb loss. The perceptions of individuals with upper extremity limb loss on patient selection criteria may enable vascularized composite allotransplantation centers to improve criteria to avoid mismatched expectations about the posttransplant vascularized composite allotransplantation experience and outcomes. Realistic patient expectations may increase patient adherence, improve outcomes, and reduce vascularized composite allotransplantation graft loss.

Methods:

We conducted in-depth interviews with civilian and military service members with upper extremity limb loss and upper extremity vascularized composite allotransplantation candidates, participants, and recipients from three US institutions. Interviews assessed perceptions of patient selection criteria for suitability as a candidate for upper extremity vascularized composite allotransplantation. Thematic analysis was used to analyze qualitative data.

Results:

A total of 50 individuals participated (66% participation rate). Most participants were male (78%), White (72%), with a unilateral limb loss (84%), and a mean age of 45 years. Six themes emerged regarding upper extremity vascularized composite allotransplantation patient selection criteria, including support for candidates who: (1) are of younger age, (2) are in good physical health, (3) have mental stability, (4) are willing to “put in the work,” (5) have specific amputation characteristics, and (6) have sufficient social support. Patients had preferences about selecting candidates with unilateral versus bilateral limb loss.

Conclusions:

Our findings suggest that numerous factors, including medical, social, and psychological characteristics, inform patients’ perceptions of patient selection criteria for upper extremity vascularized composite allotransplantation. Patient perceptions of patient selection criteria should inform the development of validated screening measures that optimize patient outcomes.
Rejecting a Narrative of Individual Deficit: A Model for Developing Antiracist Curriculum in the Health Sciences
Authors: Samarron Longorio Alexandra Elvira , Shuman Sara J. , Lockmiller Catherine , Robertson-James Candace
Published: June 2023

Recent attention to issues of systemic and institutional racism have resulted in renewed calls for antiracist teaching and learning in the health sciences. Concurrently, there is an emerging socio-political mobilization to pass legislation that limits the teaching of systemic racism. We argue that teaching and learning about racism in academic health professional curricula often has serious limitations—stagnating in a place of teaching about the social and structural determinants of health, yet emphasizing health education and individual behavioral interventions as solutions to health inequities. We present a framework that explains essential components of antiracist knowledge and action that we argue must be implemented across health sciences curricula. Using this framework, we call on health sciences educators to examine how learners engage with racism as a determinant of health and to make curricular changes that provide opportunities to learn about and engage with antiracist actions.
Co-opting “Danger” in Specialized Media for the Police
Authors: Gordon Daanika , Nadel Peter
Published: June 2023

Widespread protests for racial justice during the summer of 2020 raised foundational questions about the role of the police in U.S. society. In this article, the authors analyze an underexplored body of media representations that perform ideological work in this context. The authors examine specialized media targeting a law enforcement audience, asking how news articles published on the Web site Police1 represented the police profession and the protests for racial justice over a two-year period. The authors map major themes using topic modeling and qualitative content analysis. They find that the articles represent police work as dangerous and heroic and as simultaneously professional, legitimate, and accountable to broader legal and political systems. In addition, articles disproportionately represent the dangers experienced by police officers relative to the dangers caused by policing. Co-opting the concept of danger may reinforce the warrior mentality of police occupational culture, while precluding recognition of the patterned and racialized harms of policing.
Employment Characteristics of Regular Salaried Employees in Urban Maharashtra
Authors: Umap Sandeep , Jain Niti
Published: June 2023

Studies on the labour market in India are increasingly debating the issue of caste-based discrimination in employment. However, there are few studies addressing the issue of regular salaried employees in urban labour market, except in the context of reservation policy. Due to the reservation policy, the issue of the representation of the schedule caste, scheduled tribes and other backward class has been addressed to a particular extent. In this context, this article attempts to analyse the status of schedule caste in employment and unemployment, participation in different occupations and industries groups, job security and social security benefits in urban labour market Maharashtra. The descriptive analysis clearly shows that a significant employment difference exists between regular salaried employees belonging to Hindu High Caste (HHC) and Schedule Caste (SC). One of the reasons that comes out for the substantial gap is the higher level of unemployment rate among educated SCs as compared to HHCs. The SCs have less representation in the high earning occupations, but contrary to this, they have high representation in the low wage-earning occupations. The share of informal SCs is high as compared to HHCs in the private sector in the state and NSS regions during 2004–2005 to 2018–2019.
Compensation for Merchant’s Circle Diagram to predict cutting force in orthogonal micro turning
Authors: Das Arnab , Agnihotri Shri Narayan , Bajpai Vivek
Published: June 2023

Cutting force for conventional orthogonal machining can be predicted by Merchant’s Circle Diagram (MCD) considering the shearing action of chip formation. However, the effect of plowing action is significant for micro turning, which has not been considered in MCD. Therefore, a large error has been observed in the prediction of cutting force in micro turning by MCD theory. In this study, a compensated model has been developed for orthogonal micro turning based on MCD. The theory has taken shearing and plowing actions into consideration. The compensated model involved material flow stress, cutting parameters, and tool geometry, including cutting edge radius. This model has predicted tangential cutting force with an average prediction error of 3.75% for micro turning of Ti6Al4V, whereas the average prediction error was 14.9% for axial cutting force.
A Case of Histoplasmosis Detected Through Bone Marrow Analysis
Authors: An Do Thi Vinh , Tung Nguyen Tuan , Ha Bui Thi Viet , Tam Vu Minh , Cuong Do Duy
Published: June 2023

Histoplasmosis is an endemic infection caused by Histoplasma capsulatum, leading to a broad spectrum of disease from asymptomatic to severe disseminated disease. To diagnose Histoplasmosis, culture remains the gold standard for the laboratory diagnosis; however, this fungus grows slowly, taking a long time 2 to 3 weeks or may take up to 8 weeks. Therefore, some other methods such as bone marrow examination play an essential role in rapid identification and early diagnosis, especially in cases of severe disseminated disease. In this case, we report a 55-year-old man with a 1-year history of gout, self-medicating (including Medrol) who was admitted to the hospital because of persistent fever and swelling of his left arm. About laboratory investigation, there was a bicytopenia (RBC and PLT), blood and pus cultures many times were negative. On the slide of the bone marrow specimen, images of yeast suspected of Histoplasma capsulatum were observed. Therefore, the patient was treated with antifungal medication, and the culture was repeated with prolonged follow-up time and positive results with H. capsulatum after 16 days. In conclusion, bone marrow test plays a significant role in the diagnosis of some fungal infections, which can contribute to an early diagnosis, especially in cases of culture and serological tests are not available or cannot be performed. Patients who present with fever and bicytopenia or pancytopenia should be performed early bone marrow test, which can support the earlier diagnosis to have appropriate treatment.
Relationship between resilience and death anxiety of the older adults during the coronavirus disease 2019 (COVID-19) pandemic
Authors: Rayatpisheh Fatemeh , Torabizadeh Camellia , Najafi Kalyani Majid , Farsi Zahra
Published: June 2023

Background

The outbreak of coronavirus disease 2019 (COVID-19) caused an increase in the incidence of physical and psychological problems, particularly in the older adult. Considering the special physical and mental health conditions of the older adult, they were more exposed to psychological problems associated with the pandemic, such as death anxiety. Therefore, assessing the psychological status of this group is necessary in order to implement appropriate interventions. The present study aimed to investigate the relationship between resilience and death anxiety in the older adult during the COVID-19 pandemic.

Methods

This descriptive-analytical study was conducted on 283 older adult people over the age of 60 years. The older adult population was selected from 11 municipal districts of Shiraz, Iran, using the cluster sampling method. The resilience and death anxiety scales were used for data collection. Data analysis was performed in SPSS version 22, using Chi-square test, t-test, and Pearson’s correlation coefficient test. A P-value less than 0.05 was considered statistically significant.

Results

The mean and standard deviation of the older adult’s resilience and death anxiety scores were 64.16 ± 9.59 and 6.3 ± 2.95, respectively. There was a significant correlation between resilience and death anxiety scores (P < 0.01, r=-0.290). Also, sex (P = 0.00) and employment status (P = 0.00) were significantly associated with the older adult’s resilience. Besides, sex (P = 0.010) and employment status (P = 0.004) were significantly related to death anxiety.

Conclusions

Our findings showcase levels of resilience and death anxiety in older adults during the covid-19 pandemic and suggest that resilience and death anxiety are inversely linked. This has implications on policy planning for future major health events.
Prevalence and factors associated with sputum smear non-conversion after two months of tuberculosis treatment among smear-positive pulmonary tuberculosis patients in Rwanda: a cross-sectional study
Authors: Gatete Gaetan , Njunwa Kato J , Migambi Patrick , Ntaganira Joseph , Ndagijimana Albert
Published: June 2023

Background

Non-conversion of sputum smear prolongs the infectivity of pulmonary tuberculosis patients and has been associated with unfavorable tuberculosis (TB) treatment outcomes. Nevertheless, there is a limited evidence on predictors of sputum smear non-conversion among smear-positive PTB (SPPTB) patients in Rwanda. Therefore, this study aimed to determine the factors associated with sputum smear non-conversion after two months of treatment among SPPTB patients in Rwanda.

Methods

A cross-sectional study was conducted among SPPTB patients registered in the national electronic TB reporting system by all health facilities countrywide (Rwanda) from July 2019 to June 2021. Eligible patients who had completed the first two months of anti-TB treatment and with smear results at the end of the second month of treatment were included in the study. Bivariate and multivariate logistic regression analyses were done using STATA version 16 to determine the factors associated with sputum smear non-conversion. Adjusted odds ratio (OR), 95% confidence interval (CI), and p-value < 0.05 was considered statistically significant.

Results

This study included 7,211 patients. Of them, 632 (9%) patients had sputum smear non-conversion at the end of the second month of treatment. In multivariate logistic regression analysis, age groups of 20–39 years (AOR = 1.7, 95% CI: 1.0-2.8) and 40–59 years (AOR:2, 95% CI: 1.1–3.3), history of first-line TB treatment failure (AOR = 2, 95% CI: 1.1–3.6), follow-up by community health workers(CHWs) (AOR = 1.2, 95% CI: 1.0-1.5), BMI < 18.5 at TB treatment initiation (AOR = 1.5, 95% CI: 1.2–1.8), and living in Northern Province of Rwanda (AOR = 1.4, 95% CI: 1.0–2.0), were found to be significantly associated with sputum smear non-conversion after two months of treatment.

Conclusion

Sputum smear non-conversion among SPPTB patients remains low in Rwanda compared to countries of similar health care setting. Identified risk factors for sputum smear non-conversion among SPPTB patients in Rwanda were age (20–39 years, 40–59 years), history of first-line TB treatment failure, follow up by CHWs, BMI < 18.5 at TB treatment initiation and residence (Northern province).
Molecular and clinical characterization of PTRF in glioma via 1,022 samples
Authors: Sun Si , Yang Changlin , Wang Kuanyu , Huang Ruoyu , Zhang Ke-nan , Liu Yanwei , Cao Zhi , Zhao Zheng , Jiang Tao
Published: June 2023

Polymerase I and transcript release factor (PTRF) plays a role in the regulation of gene expression and the release of RNA transcripts during transcription, which have been associated with various human diseases. However, the role of PTRF in glioma remains unclear. In this study, RNA sequencing (RNA-seq) data (n = 1022 cases) and ﻿whole-exome sequencing (WES) data (n = 286 cases) were used to characterize the PTRF expression features. ﻿Gene ontology (GO) functional enrichment analysis was used to assess the biological implication of changes in PTRF expression. As a result, the expression of PTRF was associated with ﻿malignant progression in gliomas. Meanwhile, somatic mutational profiles and copy number variations (CNV) revealed the glioma subtypes classified by PTRF expression showed distinct genomic alteration. Furthermore, GO functional enrichment analysis suggested that PTRF expression was associated with cell migration and angiogenesis, particularly during an immune response. Survival analysis confirmed that a high expression of PTRF is associated with a poor prognosis. In summary, PTRF may be a valuable factor for the diagnosis and treatment target of glioma.
Epidemiology and risk factors for thrombosis in children and newborns: systematic evaluation and meta-analysis
Authors: Song Shuang , Li Zhuowei , Zhao Guozhen , Li Xintong , Wang Runying , Li Bo , Liu Qingquan
Published: June 2023

Background

Thrombosis is a serious condition in children and neonates. However, the risk factors for thrombosis have not been conclusively determined. This study aimed to identify the risk factors for thrombosis in children and neonates in Intensive Care Unit (ICU) through a meta-analysis to better guide clinical treatment.

Methods

A systematic search of electronic databases (PubMed, Embase, Cochrane Library, WOS, CNKI, Wanfang, VIP) was conducted to retrieve studies from creation on 23 May 2022. Data on the year of publication, study design, country of origin, number of patients/controls, ethnicity, and type of thrombus were extracted. The publication bias and heterogeneity between studies were assessed, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed or random effects models.

Results

A total of 18 studies met the inclusion criteria. The incidence of thrombosis in children was 2% per year (95% CI 1%-2%, P < 0.01). Infection and sepsis (OR = 1.95, P < 0.01), CVC (OR = 3.66, [95%CL 1.78–7.51], P < 0.01), mechanical ventilation (OR = 2.1, [95%CL1.47–3.01], P < 0.01), surgery (OR = 2.25, [95%CL1.2–4.22], P < 0.01), respiratory distress (OR = 1.39, [95%CL0.42–4.63], P < 0.01), ethnicities (OR = 0.88, [95%CL 0.79–0.98], P = 0.78), gestational age (OR = 1.5, [95%CL1.34–1.68], P = 0.65)were identified as risk factors for thrombosis.

Conclusions

This meta-analysis suggests that CVC, Surgery, mechanical ventilation, Infection/sepsis, gestational age, Respiratory distress, and different ethnicities are risk factors for thrombosis in children and neonates in ICU. These findings may help clinicians to identify high-risk patients and develop appropriate prevention strategies.

Trial registration

PROSPERO (CRD 42022333449).
Enhancing the effectiveness of infectious disease health education for children and adolescents in China: a national multicenter school-based trial
Authors: Wang Xinxin , Liu Jieyu , Wu Yu , Su Binbin , Chen Manman , Ma Qi , Ma Tao , Chen Li , Zhang Yi , Dong Yanhui , Song Yi , Ma Jun
Published: June 2023

Background

Infectious diseases pose a significant risk to the health and well-being of children and adolescents, and can even be life-threatening. Thus, our study aimed to explore the effectiveness of health education based on the social-ecological model in improving the knowledge of infectious diseases among this vulnerable population.

Methods

This study was a school-based intervention conducted in seven Chinese provinces in 2013, involving a total of 26,591 children and adolescents in the intervention group and 24,327 in the control group. The intervention group received a comprehensive health intervention based on the social-ecological model (SEM) over six months, which included a supportive environment, health education on infectious diseases, guidance on self-monitoring infectious disease-related behaviors, and other measures. Data on infectious disease-related knowledge and other characteristics were collected through questionnaires. The main outcome measure will be the difference in the effectiveness of health education regarding infectious diseases in children and adolescents between baseline and post-intervention. A mixed-effects regression model was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to assess the impact of infectious disease-related interventions on the participants.

Results

We utilized a socioecological model as the foundation for a six-month health education program on infectious diseases targeting children and adolescents in the intervention group. At the individual and community levels, the correct rate of health behavior related to infectious diseases in the intervention group was higher than that in the control group (P < 0.05), the ORs (95% CI) were 0.94 (0.90–0.99) and 0.94 (0.89–0.99), respectively. But the intervention effect was not significant at the interpersonal level. The intervention effect at the organizational level was obvious, with an increase in opportunities for children and adolescents to acquire knowledge of infectious diseases from courses and lectures, teachers, and doctors, (all P < 0.05), with the ORs (95% CI) of 0.92 (0.87–0.97) and 0.86 (0.83–0.94), respectively. However, there was no significant difference between the intervention group and the control group in school infectious disease health education policy.

Conclusion

Enhancing health education regarding infectious diseases is crucial in promoting comprehensive prevention and control measures among children and adolescents. Nevertheless, it remains imperative to reinforce health education on infectious diseases at the interpersonal and policy levels. This holds significant reference value for mitigating childhood infectious diseases in the post-COVID-19 era.
Single-cell RNA-sequencing of stria vascularis cells in the adult Slc26a4-/- mouse
Authors: Koh Jin-Young , Affortit Corentin , Ranum Paul T. , West Cody , Walls William D. , Yoshimura Hidekane , Shao Jian Q. , Mostaert Brian , Smith Richard J.H.
Published: June 2023

Background

The primary pathological alterations of Pendred syndrome are endolymphatic pH acidification and luminal enlargement of the inner ear. However, the molecular contributions of specific cell types remain poorly characterized. Therefore, we aimed to identify pH regulators in pendrin-expressing cells that may contribute to the homeostasis of endolymph pH and define the cellular pathogenic mechanisms that contribute to the dysregulation of cochlear endolymph pH in Slc26a4−/− mice.

Methods

We used single-cell RNA sequencing to identify both Slc26a4-expressing cells and Kcnj10-expressing cells in wild-type (WT, Slc26a4+/+) and Slc26a4−/− mice. Bioinformatic analysis of expression data confirmed marker genes defining the different cell types of the stria vascularis. In addition, specific findings were confirmed at the protein level by immunofluorescence.

Results

We found that spindle cells, which express pendrin, contain extrinsic cellular components, a factor that enables cell-to-cell communication. In addition, the gene expression profile informed the pH of the spindle cells. Compared to WT, the transcriptional profiles in Slc26a4−/− mice showed downregulation of extracellular exosome-related genes in spindle cells. Immunofluorescence studies in spindle cells of Slc26a4−/− mice validated the increased expression of the exosome-related protein, annexin A1, and the clathrin-mediated endocytosis-related protein, adaptor protein 2.

Conclusion

Overall, cell isolation of stria vascularis from WT and Slc26a4−/− samples combined with cell type-specific transcriptomic analyses revealed pH-dependent alternations in spindle cells and intermediate cells, inspiring further studies into the dysfunctional role of stria vascularis cells in SLC26A4-related hearing loss.
Combination effects of amino acid transporter LAT1 inhibitor nanvuranlat and cytotoxic anticancer drug gemcitabine on pancreatic and biliary tract cancer cells
Authors: Nishikubo Kou , Ohgaki Ryuichi , Liu Xingming , Okanishi Hiroki , Xu Minhui , Endou Hitoshi , Kanai Yoshikatsu
Published: June 2023

Background

Cytotoxic anticancer drugs widely used in cancer chemotherapy have some limitations, such as the development of side effects and drug resistance. Furthermore, monotherapy is often less effective against heterogeneous cancer tissues. Combination therapies of cytotoxic anticancer drugs with molecularly targeted drugs have been pursued to solve such fundamental problems. Nanvuranlat (JPH203 or KYT-0353), an inhibitor for L-type amino acid transporter 1 (LAT1; SLC7A5), has novel mechanisms of action to suppress the cancer cell proliferation and tumor growth by inhibiting the transport of large neutral amino acids into cancer cells. This study investigated the potential of the combined use of nanvuranlat and cytotoxic anticancer drugs.

Methods

The combination effects of cytotoxic anticancer drugs and nanvuranlat on cell growth were examined by a water-soluble tetrazolium salt assay in two-dimensional cultures of pancreatic and biliary tract cancer cell lines. To elucidate the pharmacological mechanisms underlying the combination of gemcitabine and nanvuranlat, we investigated apoptotic cell death and cell cycle by flow cytometry. The phosphorylation levels of amino acid-related signaling pathways were analyzed by Western blot. Furthermore, growth inhibition was examined in cancer cell spheroids.

Results

All the tested seven types of cytotoxic anticancer drugs combined with nanvuranlat significantly inhibited the cell growth of pancreatic cancer MIA PaCa-2 cells compared to their single treatment. Among them, the combined effects of gemcitabine and nanvuranlat were relatively high and confirmed in multiple pancreatic and biliary tract cell lines in two-dimensional cultures. The growth inhibitory effects were suggested to be additive but not synergistic under the tested conditions. Gemcitabine generally induced cell cycle arrest at the S phase and apoptotic cell death, while nanvuranlat induced cell cycle arrest at the G0/G1 phase and affected amino acid-related mTORC1 and GAAC signaling pathways. In combination, each anticancer drug basically exerted its own pharmacological activities, although gemcitabine more strongly influenced the cell cycle than nanvuranlat. The combination effects of growth inhibition were also verified in cancer cell spheroids.

Conclusions

Our study demonstrates the potential of first-in-class LAT1 inhibitor nanvuranlat as a concomitant drug with cytotoxic anticancer drugs, especially gemcitabine, on pancreatic and biliary tract cancers.
Control of the injection velocity of embolic agents in embolization treatment
Authors: Ren Dongcheng , Zhou Bo , Li Jiasheng , Guo Shijie , Guo Baolei
Published: June 2023

Background

Embolization is a common treatment method for tumor-targeting, anti-organ hyper-function, and hemostasis. However, the injection of embolic agents largely depends on the experiences of doctors, and doctors need to work in an X-ray environment that hurts their health. Even for a well-trained doctor, complications such as ectopic embolism caused by excessive embolic agents are always inevitable.

Results

This paper established a flow control curve model for embolic injection based on local arterial pressure. The end-vessel network was simplified as a porous media. The hemodynamic changes at different injection velocities and embolization degrees were simulated and analyzed. Sponge, a typical porous medium, was used to simulate the blocking and accumulation of embolic agents by capillary networks in the in vitro experimental platform.

Conclusions

The simulation and experimental results show that the local arterial pressure is closely related to the critical injection velocity of the embolic agent reflux at a certain degree of embolization. The feasibility of this method for an automatic embolic injection system is discussed. It is concluded that the model of the flow control curve of embolic injection can effectively reduce the risk of ectopic embolism and shorten the time of embolic injection. The clinical application of this model is of great value in reducing radiation exposure and improving the success rate of interventional embolization.
Awareness and utilization of smoking cessation clinics in Saudi Arabia, findings from the 2019 Global Adult Tobacco Survey
Authors: Monshi Sarah S. , Alanazi Abdullah M. M. , Alzahrani Ali M. , Alzhrani Abdulrhman A. , Arbaein Turky J. , Alharbi Khulud K. , Z. Alqahtani Mansour , Alzahrani Ali H. , A. Elkhobby Ahmed , Almazrou Aljoharah M. , Al-Zalabani Abdulmohsen H.
Published: June 2023

Background

Tobacco use remains a leading cause of premature death. To combat tobacco use, the Ministry of Health (MOH) improved access to smoking cessation clinics (SCCs) by developing fixed SCCs and mobile SCCs, which move based on demand across locations. The goal of this study was to investigate awareness and utilization of SCCs among tobacco users in Saudi Arabia and the factors that influence their awareness and utilization.

Method

This cross-sectional study used the 2019 Global Adult Tobacco Survey. Three outcome variables were employed, including tobacco users’ awareness of fixed SCCs, mobile SCCs, and utilization of fixed SCCs. Several independent variables were examined, including sociodemographic characteristics and tobacco use. Multivariable logistic regression analyses were performed.

Results

One thousand six hundred sixty-seven tobacco users were included in this study. There were 60%, 26%, and 9% of tobacco users who were aware of fixed SCCs, aware of mobile SCCs, and visited fixed SCCs, respectively. The likelihood of being aware of SCCs increased among users residing in urban areas (fixed SCCs: OR = 1.88; 95% CI = 1.31–2.68; mobile SCCs: OR = 2.09; CI = 1.37–3.17) while it decreased among those reported self-employed (fixed SCCs: OR = 0.31; CI = 0.17–0.56; mobile SCCs: OR = 0.42; CI = 0.20–0.89). The likelihood of visiting fixed SCCs increased among educated tobacco users aged 25–34 (OR = 5.61; CI = 1.73–18.21) and 35–44 (OR = 4.22; CI = 1.07–16.64) while the odds of visiting SCCs decreased among those who were working in the private sector (OR = 0.26; CI = 0.09–0.73).

Conclusion

The decision to quit smoking must be supported by an effective healthcare system that provides accessible and affordable smoking cessation services. Knowing the factors that influence the awareness and utilization of SCCs would help policymakers dedicate efforts targeting those who desire to quit smoking yet face limitations in using SCCs.
A novel dammarane triterpenoid alleviates atherosclerosis by activating the LXRα pathway
Authors: Huang Yan , Ran Xiaodong , Liu Hongmei , Luo Mingming , Qin Yiyu , Yan Jinqiong , Li Xiaohui , Jia Yi
Published: June 2023

Background

We have previously demonstrated that ginsenoside compound K can attenuate the formation of atherosclerotic lesions. Therefore, ginsenoside compound K has potential for atherosclerosis therapy. How to improve the druggability and enhance the antiatherosclerotic activity of ginsenoside compound K are the core problems in the prevention and treatment of atherosclerosis. CKN is a ginsenoside compound K derivative that was previously reported to have excellent antiatherosclerotic activity in vitro, and we have applied for international patents for it.

Methods

Male C57BL/6 ApoE−/− mice were fed a high-fat and high-choline diet to induce atherosclerosis and were subjected to in vivo studies. In vitro, the CCK-8 method was applied to evaluate cytotoxicity in macrophages. Foam cells were utilized, and cellular lipid determination was performed for in vitro studies. The area of atherosclerotic plaque and fatty infiltration of the liver were measured by image analysis. Serum lipid and liver function were determined by a seralyzer. Immunofluorescence and western blot analysis were conducted to explore the alterations in the expression levels of lipid efflux-related proteins. Molecular docking, reporter gene experiments and cellular thermal shift assays were used to verify the interaction between CKN and LXRα.

Results

After confirming the therapeutic effects of CKN, molecular docking, reporter gene experiments and cellular thermal shift assays were used to predict and investigate the antiatherosclerotic mechanisms of CKN. CKN exhibited the greatest potency, with a 60.9% and 48.1% reduction in en face atherosclerotic lesions on the thoracic aorta and brachiocephalic trunk, reduced plasma lipid levels and decreased foam cell levels in the vascular plaque content in HHD-fed ApoE−/− mice. Moreover, CKN in the present study may exert its antiatherosclerotic effects through activated ABCA1 by promoting LXRα nuclear translocation and reducing the adverse effects of LXRα activation.

Conclusions

Our results revealed that CKN prevented the formation of atherosclerosis in ApoE−/− mice by activating the LXRα pathway.
Microwave therapy for the treatment of plantar warts
Authors: Hagon Wendy , Hagon Jonathan , Noble Greer , Brenton‐Rule Angela , Stewart Sarah , Bristow Ivan
Published: June 2023

Background

Plantar warts, or verrucae plantaris, are common lesions causing considerable pain during weightbearing activity. Although current treatment modalities have low success rates, microwave therapy has been introduced as a promising intervention. This study aimed to determine the effectiveness of microwave therapy for the treatment of plantar warts and to determine the clinical factors associated with plantar wart resolution.

Methods

A retrospective analysis of 150 plantar warts from 45 patients treated with microwave therapy was undertaken. Binomial regression was conducted to explore clinical characteristics (age, gender, immunosuppression, impaired healing, multiple vs single wart, location of lesion, lesion diameter) associated with lesion resolution.

Results

Of the total 150 plantar warts treated with microwave therapy, 125 (83.3%) warts resolved and 25 (17%) warts did not resolve. The mean (SD) total treatment sessions for resolved lesions was 2.8 (1.0). Decreasing age (P = 0.046) was the only clinical characteristic associated with resolution.

Conclusions

This retrospective study has shown that plantar warts may be resolved with two to three sessions of microwave therapy, which may be more successful in younger populations.
Critically buried avalanche victims can develop severe hypothermia in less than 60 min
Authors: Rauch Simon , Kompatscher Julia , Clara Andreas , Öttl Iris , Strapazzon Giacomo , Kaufmann Marc
Published: June 2023

Background

A major challenge in the management of avalanche victims in cardiac arrest is differentiating hypothermic from non-hypothermic cardiac arrest, as management and prognosis differ. Duration of burial with a cutoff of 60 min is currently recommended by the resuscitation guidelines as a parameter to aid in this differentiation However, the fastest cooling rate under the snow reported so far is 9.4 °C per hour, suggesting that it would take 45 min to cool below 30 °C, which is the temperature threshold below which a hypothermic cardiac arrest can occur.

Case presentation

We describe a case with a cooling rate of 14 °C per hour, assessed on site with an oesophageal temperature probe. This is by far the most rapid cooling rate after critical avalanche burial reported in the literature and further challenges the recommended 60 min threshold for triage decisions. The patient was transported under continuous mechanical CPR to an ECLS facility and rewarmed with VA-ECMO, although his HOPE score was 3% only. After three days he developed brain death and became an organ donor.

Conclusions

With this case we would like to underline three important aspects: first, whenever possible, core body temperature should be used instead of burial duration to make triage decisions. Second, the HOPE score, which is not well validated for avalanche victims, had a good discriminatory ability in our case. Third, although extracorporeal rewarming was futile for the patient, he donated his organs. Thus, even if the probability of survival of a hypothermic avalanche patient is low based on the HOPE score, ECLS should not be withheld by default and the possibility of organ donation should be considered.
Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites
Authors: Reers Ashley B. , Bautista Rodriel , McLellan James , Morales Beatriz , Garza Rolando , Bol Sebastiaan , Hanson Kirsten K. , Bunnik Evelien M.
Published: June 2023

Gene expression in malaria parasites is subject to various layers of regulation, including histone post-translational modifications (PTMs). Gene regulatory mechanisms have been extensively studied during the main developmental stages ofPlasmodiumparasites inside erythrocytes, from the ring stage following invasion to the schizont stage leading up to egress. However, gene regulation in merozoites that mediate the transition from one host cell to the next is an understudied area of parasite biology. Here, we sought to characterize gene expression and the corresponding histone PTM landscape during this stage of the parasite lifecycle through RNA-seq and ChIP-seq onP. falciparumblood stage schizonts, merozoites, and rings, as well asP. bergheiliver stage merozoites. In both hepatic and erythrocytic merozoites, we identified a subset of genes with a unique histone PTM profile characterized by a region of H3K4me3 depletion in their promoter. These genes were upregulated in hepatic and erythrocytic merozoites and rings, had roles in protein export, translation, and host cell remodeling, and shared a DNA motif. These results indicate that similar regulatory mechanisms may underlie merozoite formation in the liver and blood stages. We also observed that H3K4me2 was deposited in gene bodies of gene families encoding variant surface antigens in erythrocytic merozoites, which may facilitate switching of gene expression between different members of these families. Finally, H3K18me and H2K27me were uncoupled from gene expression and were enriched around the centromeres in erythrocytic schizonts and merozoites, suggesting potential roles in the maintenance of chromosomal organization during schizogony. Together, our results demonstrate that extensive changes in gene expression and histone landscape occur during the schizont-to-ring transition to facilitate productive erythrocyte infection. The dynamic remodeling of the transcriptional program in hepatic and erythrocytic merozoites makes this stage attractive as a target for novel anti-malarial drugs that may have activity against both the liver and blood stages.
PARP-dependent and NAT10-independent acetylation of N4-cytidine in RNA appears in UV-damaged chromatin
Authors: Svobodová Kovaříková Alena , Stixová Lenka , Kovařík Aleš , Bártová Eva
Published: June 2023

RNA modifications have been known for many years, but their function has not been fully elucidated yet. For instance, the regulatory role of acetylation on N4-cytidine (ac4C) in RNA can be explored not only in terms of RNA stability and mRNA translation but also in DNA repair. Here, we observe a high level of ac4C RNA at DNA lesions in interphase cells and irradiated cells in telophase. Ac4C RNA appears in the damaged genome from 2 to 45 min after microirradiation. However, RNA cytidine acetyltransferase NAT10 did not accumulate to damaged sites, and NAT10 depletion did not affect the pronounced recruitment of ac4C RNA to DNA lesions. This process was not dependent on the G1, S, and G2 cell cycle phases. In addition, we observed that the PARP inhibitor, olaparib, prevents the recruitment of ac4C RNA to damaged chromatin. Our data imply that the acetylation of N4-cytidine, especially in small RNAs, has an important role in mediating DNA damage repair. Ac4C RNA likely causes de-condensation of chromatin in the vicinity of DNA lesions, making it accessible for other DNA repair factors involved in the DNA damage response. Alternatively, RNA modifications, including ac4C, could be direct markers of damaged RNAs.
Identification of a methylation panel as an alternative triage to detect CIN3+ in hrHPV-positive self-samples from the population-based cervical cancer screening programme
Authors: de Waard J. , Bhattacharya A. , de Boer M. T. , van Hemel B. M. , Esajas M. D. , Vermeulen K. M. , de Bock G. H. , Schuuring E. , Wisman G. B. A.
Published: June 2023

Background

The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to cervical scraping by a general practitioner (GP), women are offered self-sampling to increase participation. Because cytological examination on self-sampled material is not feasible, collection of cervical samples from hrHPV-positive women by a GP is required. This study aims to design a methylation marker panel to detect CIN3 or worse (CIN3+) in hrHPV-positive self-samples from the Dutch PBS as an alternative triage test for cytology.

Methods

Fifteen individual host DNA methylation markers with high sensitivity and specificity for CIN3+ were selected from literature and analysed using quantitative methylation-specific PCR (QMSP) on DNA from hrHPV-positive self-samples from 208 women with CIN2 or less (< CIN2) and 96 women with CIN3+. Diagnostic performance was determined by area under the curve (AUC) of receiver operating characteristic (ROC) analysis. Self-samples were divided into a train and test set. Hierarchical clustering analysis to identify input methylation markers, followed by model-based recursive partitioning and robustness analysis to construct a predictive model, was applied to design the best marker panel.

Results

QMSP analysis of the 15 individual methylation markers showed discriminative DNA methylation levels between < CIN2 and CIN3+ for all markers (p < 0.05). The diagnostic performance analysis for CIN3+ showed an AUC of ≥ 0.7 (p < 0.001) for nine markers. Hierarchical clustering analysis resulted in seven clusters with methylation markers with similar methylation patterns (Spearman correlation> 0.5). Decision tree modeling revealed the best and most robust panel to contain ANKRD18CP, LHX8 and EPB41L3 with an AUC of 0.83 in the training set and 0.84 in the test set. Sensitivity to detect CIN3+ was 82% in the training set and 84% in the test set, with a specificity of 74% and 71%, respectively. Furthermore, all cancer cases (n = 5) were identified.

Conclusion

The combination of ANKRD18CP, LHX8 and EPB41L3 revealed good diagnostic performance in real-life self-sampled material. This panel shows clinical applicability to replace cytology in women using self-sampling in the Dutch PBS programme and avoids the extra GP visit after a hrHPV-positive self-sampling test.
Vitamin B12 produced by Cetobacterium somerae improves host resistance against pathogen infection through strengthening the interactions within gut microbiota
Authors: Qi Xiaozhou , Zhang Yong , Zhang Yilin , Luo Fei , Song Kaige , Wang Gaoxue , Ling Fei
Published: June 2023

Background

Pathogen infections seriously affect host health, and the use of antibiotics increases the risk of the emergence of drug-resistant bacteria and also increases environmental and health safety risks. Probiotics have received much attention for their excellent ability to prevent pathogen infections. Particularly, explaining mechanism of action of probiotics against pathogen infections is important for more efficient and rational use of probiotics and the maintenance of host health.

Results

Here, we describe the impacts of probiotic on host resistance to pathogen infections. Our findings revealed that (I) the protective effect of oral supplementation with B. velezensis against Aeromonas hydrophila infection was dependent on gut microbiota, specially the anaerobic indigenous gut microbe Cetobacterium; (II) Cetobacterium was a sensor of health, especially for fish infected with pathogenic bacteria; (III) the genome resolved the ability of Cetobacterium somerae CS2105-BJ to synthesize vitamin B12 de novo, while in vivo and in vitro metabolism assays also showed the ability of Cetobacterium somerae CS2105-BJ to produce vitamin B12; (IV) the addition of vitamin B12 significantly altered the gut redox status and the gut microbiome structure and function, and then improved the stability of the gut microbial ecological network, and enhanced the gut barrier tight junctions to prevent the pathogen infection.

Conclusion

Collectively, this study found that the effect of probiotics in enhancing host resistance to pathogen infections depended on function of B12 produced by an anaerobic indigenous gut microbe, Cetobacterium. Furthermore, as a gut microbial regulator, B12 exhibited the ability to strengthen the interactions within gut microbiota and gut barrier tight junctions, thereby improving host resistance against pathogen infection.
Roles, outcomes, and enablers within research partnerships: A rapid review of the literature on patient and public involvement and engagement in health research
Authors: Karlsson Anne Wettergren , Kragh-Sørensen Anne , Børgesen Kirsten , Behrens Karsten Erik , Andersen Torben , Kidholm Maiken Langhoff , Rothmann Mette Juel , Ketelaar Marjolijn , Janssens Astrid
Published: June 2023

Background

Recent studies mention a need to investigate partnership roles and dynamics within patient and public involvement and engagement (PPIE) in health research, and how impact and outcomes are achieved. Many labels exist to describe involvement processes, but it is unknown whether the label has implications on partnerships and outcomes. This rapid review investigates how roles between patients, relatives and researchers in a broad variety of PPIE activities in health research are described in peer reviewed papers and explores what enables these partnerships.

Methods

Rapid review of articles published between 2012 and February 2022 describing, evaluating, or reflecting on experiences of PPIE in health research. All research disciplines and research areas were eligible. Four databases (Medline, Embase, PsychInfo and CINAHL) were searched between November 2021 and February 2022. We followed PRISMA guidelines and extracted descriptive factors: year, origin, research area and discipline, study focus, framework used and co-authorship. On a selection of articles, we performed a narrative analysis of partnership roles using Smits et al.’s. Involvement Matrix. Lastly, we performed a meta synthesis of reported enablers and outcomes of the partnerships. Patients and Relatives (PRs) have been involved in the whole rapid review process and are co-authors of this article.

Results

Seventy articles from various research disciplines and areas were included. Forty articles were selected for a narrative analysis of the role description of PRs and researchers, and a meta synthesis of enablers and outcomes. Most articles described researchers as decision-makers throughout the research cycle. PRs most often were partners when they were included as co-authors; they were mostly partners in the design, analysis, write-up, and dissemination stages. Enablers of partnerships included: PR training, personality of PRs and communication skills, trust, remuneration and time.

Conclusions

Researchers’ decision-making roles gives them control of where and when to include PRs in their projects. Co-authorship is a way of acknowledging patients’ contributions which may lead to legitimation of their knowledge and the partnership. Authors describe common enablers, which can help future partnership formation.
Financial Toxicity Order Set: Implementing a Simple Intervention to Better Connect Patients With Resources
Authors: Thom Bridgette , Sokolowski Stefania , Abu-Rustum Nadeem R. , Allen-Dicker Joshua , Caramore Amy , Chino Fumiko , Doyle Stephanie , Fitzpatrick Christine , Gany Francesca , Liebhaber Allison , Newman Tiffanny , Rao Nisha , Tappen Johanna , Aviki Emeline M.
Published: June 2023

PURPOSE

Financial toxicity of cancer treatment is well described in the literature, including characterizations of its risk factors, manifestations, and consequences. There is, however, limited research on interventions, particularly those at the hospital level, to address the issue.

METHODS

From March 1, 2019, to February 28, 2022, a multidisciplinary team conducted a three-cycle Plan-Do-Study-Act (PDSA) process to develop, test, and implement an electronic medical record (EMR) order set to directly refer patients to a hospital-based financial assistance program. The cycles included an assessment of the efficacy of our current practice in connecting patients experiencing financial hardship with assistance, the development and piloting of the EMR referral order, and the broad implementation of the order set across our institution.

RESULTS

In PDSA cycle 1, we found that approximately 25% of patients at our institution experienced some form of financial hardship, but most patients were not connected to available resources because of our referral mechanism. In PDSA cycle 2, the pilot referral order set was deemed feasible and received positive feedback. Over the 12-month study period (March 1, 2021-February 28, 2022) of PDSA cycle 3, 718 orders were placed for 670 unique patients across interdisciplinary providers from 55 treatment areas. These referrals resulted in at least $850,000 in US dollars (USD) in financial aid in 38 patients (mean = $22,368 USD).

CONCLUSION

The findings from our three-cycle PDSA quality improvement project demonstrate the feasibility and efficacy of interdisciplinary efforts to develop a hospital-level financial toxicity intervention. A simple referral mechanism can empower providers to connect patients in need with available resources.