bluuebunny/crossref_metadata_2025 huggingface dataset:
A multilevel intervention to promote HPV vaccination among young adults in Texas: protocol for a randomized controlled trial
Authors: Lu Qian , Dawkins-Moultin Lenna , Cho Dalnim , Tan Naomi Q. P. , Hopfer Suellen , Li Yisheng , Ramondetta Lois , Xu Yusi , Lun Di , Chen Minxing
Published: June 2024

Background

Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol.

Methods

The study uses a two by three factorial design. A total of 1200 young adults in Texas, age 18–26 years, who have not been previously fully vaccinated against HPV will be randomly assigned to one of six conditions to receive: (1) standard CDC information about HPV vaccination (control); (2) video narratives about HPV vaccination; (3) written narratives about HPV vaccination; or (4–6) enhanced access to HPV vaccine combined with (4) standard CDC information, (5) video narratives, or (6) written narratives. The two primary outcomes are the rate of HPV vaccination initiation by 3-month follow-up and rate of HPV vaccination completion by 9-month follow-ups. We will determine the impact of the individual level intervention (i.e., persuasive narratives through video or written format), the systemic level intervention (i.e., enhanced access to HPV vaccines), and the combination of both levels, on HPV vaccination initiation and completion. We will also use purposive sampling to select participants to take part in semi-structured interviews/focus groups to better understand the mechanisms of the intervention.

Discussion

Recruitment and data collection began in March 2022. We expect to complete data collection by March 2026. We expect that narratives, enhanced access, and the combination of both will improve HPV vaccination initiation and completion rates among young adults. If proven successful, these individual- and system-level interventions can be easily disseminated in regions with low HPV vaccination rates to improve HPV vaccination, and ultimately decrease HPV-related cancer burden.

Trial Registration

NCT05057312.
Stress management: how does the academic staff cope with it? a cross-sectional study at the university of Udine
Authors: Vacchi Olivia Giulia Bianca , Menis Diana , Scarpis Enrico , Tullio Annarita , Piciocchi Benedetta , Gazzetta Silvia , Del Pin Massimo , Ruscio Edoardo , Brusaferro Silvio , Brunelli Laura
Published: June 2024

Background

Increasing work-related stress in academia can have an impact on physical and mental health. The aim of this study was to analyse the coping strategies of staff employed at the University of Udine and to verify whether sociodemographic data, professional position, and the presence of anxiety or depression symptoms are related to the use of different coping strategies.

Methods

We conducted a cross-sectional study between June and December 2020 using the Brief COPE questionnaire. We correlated coping strategies with professional position, sociodemographic data, and the presence of anxiety or depressive symptoms measured with the Patient Health Questionnaire–9 and the General Anxiety Disorder–7.

Results

A total of 366 people participated in the study, including 109 junior academics, 146 senior academics, and 111 administrative staff (response rate 23.6%). The three most frequently used coping strategies in terms of approach coping style were planning (6.77 ± 1.41), active coping (6.58 ± 1.45) and acceptance (6.23 ± 1.44). Women were more likely than men to report using approach and avoidant coping strategies (p < 0.001). Positive reframing and religion were most commonly used by administrative staff (p < 0.05), in contrast to junior academics, who were more likely to use substances and self-blame (p < 0.05). Anxiety was found to correlate with self-blame (OR 1.94) as a coping strategy, while depression was associated with venting (OR 2.83), self-blame (OR 3.27), and humor (OR 3.02).

Conclusion

Identifying profiles of coping strategies can help higher education institutions to implement support strategies for the academic community, ultimately promoting healthier lives and more effective teaching and research. Our study has shown that women and junior academics among staff at the Udine University would benefit from a tailored health promotion intervention that encourages the use of approach coping styles to reduce their risk of developing anxiety and depressive symptoms.
Trends in prevalence of arthritis by race among adults in the United States, 2011–2018
Authors: Xu Shenghao , Shen Xianyue , Chen Bo , Sun Yingqiao , Tang Xiongfeng , Xiao Jianlin , Qin Yanguo
Published: June 2024

Background

There is currently a lack of comprehensive prevalence information on arthritis and its various classifications among adults in the U.S., particularly given the notable absence of detailed data regarding the Asian population. We examined the trends in the prevalence of arthritis, including osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and other types of arthritis, among U.S. adults by race between 2011 and 2018.

Methods

We analyzed data from the National Health and Nutrition Examination Survey (NHANES), spanning from 2011 to 2018. Our study focused on a nationally representative sample of U.S. adults aged 20 and older. Participants who answered “y es” to the research question “Doctors ever said you had arthritis?” were classified as having arthritis. Further classification into specific diseases was based on responses to the question “Which type of arthritis was it?” with options including “OA or degenerative arthritis, ” “RA, ” “PsA, ” or “Other. ”

Results

We analyzed 22,566 participants from NHANES (2011–2018), averaging 44.8 years, including 10,927 males. The overall arthritis prevalence rose significantly from 22.98% (95% CI: 21.47–24.55%) in 2011–12 to 27.95% (95% CI: 26.20–29.76%) in 2017–18 (P for trend < 0.001). OA increased from 12.02% (95% CI: 10.82–13.35%) in 2011 to 14.93% (95% CI: 13.47–16.51%) in 2018 (P for trend < 0.001). RA and PsA remained stable (P for trend = 0.220 and 0.849, respectively), while other arthritis rose from 2.03% (95% CI: 1.54–2.67%) in 2011–12 to 3.14% (95% CI: 2.56–3.86%) in 2017–18 (P for trend = 0.001). In Whites, Asians, and other races , arthritis and RA prevalence increased significantly (P for trend < 0.05). OA and other arthritis rose in Whites and other races (P for trend < 0.05), but no significant change occurred in the black population. The prevalence of PsA remained stable across all racial groups, with no statistically significant changes.

Conclusions

In this nationally representative U.S. adult survey spanning 2011 to 2018, we identified a rising prevalence trend in arthritis, OA, and other arthritis, with notable variations among different racial groups.
Prevalence, patterns, and determinants of breastfeeding cessation among mothers of children under 24 months in Uganda
Authors: Nakaggwa Florence , Kimuli Derrick , Namuwenge Norah , Nsubuga Rebecca N. , Nayebare Hellen , Kaboine Louis , Baseka Immaculate , Kasule Kenneth , Nyakwezi Sheila , Sevume Solome , Mubiru Norbert , Amuron Barbara , Bukenya Daraus
Published: June 2024

Background

Breastfeeding duration is a critical component of infant and child nutrition, providing immediate and long-term benefits to both children and their mothers. This study uses data from the lot quality assurance sampling (LQAS) survey to examine the prevalence, patterns, and determinants of breastfeeding cessation in Uganda.

Methods

This study was a secondary analysis of data collected by the cross-sectional LQAS surveys in 2021 and 2022 covering 77 districts in Uganda. The LQAS survey methodology employs a systematic sampling approach to assess whether predefined quality standards are met within specific subgroups of a population. The study employed spatial analysis, bivariate analysis and logistic regression, both with and without clustering, to explore associations between independent variables and breastfeeding cessation. Unadjusted and adjusted odds ratios with 95% confidence intervals were calculated. Statistical significance was set at 5%.

Results

Overall, the study analysed 26,377 records of mothers with children under 24 months old. The mothers’ mean age was 27.9 years while that of their children was 11.0 months. While the general breastfeeding cessation rate was 17.7%, cessation was highest (49.7%) among mothers of children 18-23 months. Factors associated with increased odds of breastfeeding cessation included older child’s age, older mother’s age, using modern family planning, being pregnant and having an unknown pregnancy status. Lower odds of breastfeeding cessation were observed among mothers who; were married, lived in larger households, lived in rural residences, whose children received vitamin A supplementation and among all other regions compared to Kampala.

Conclusion

One in five mothers cessed breastfeeding before their child reached 2 years, with a significant increase in cessation odds among mothers of older children. These findings underscore the importance of interventions to promote breastfeeding continuation and adequate nutrition for non-breastfed infants, particularly in regions with high cessation rates.
Effect of flavonoids from grape seed and cranberry extracts on the microbiological activity of Streptococcus mutans: a systematic review of in vitro studies
Authors: Castellanos Jeison Stiven , Betancourt Diego Enrique , Díaz-Báez David , Baldión Paula Alejandra
Published: June 2024

Objective

To provide an overview of the available scientific evidence from in vitro studies regarding the effect induced by the flavonoids contained in grape seed extracts (GSE) and cranberry on the microbiological activity of Streptococcus mutans (S. mutans).

Methods

This systematic review was performed following the parameters of the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). Electronic and manual searches were conducted using PubMed, ScienceDirect, Web of Science, EBSCO, and Cochrane databases. Reference lists of selected articles were reviewed to identify relevant studies. The search was not limited by year and was conducted solely in English. Eligible studies comprised publications describing in vitro studies that evaluated the effect of flavonoids derived from GSE and cranberry extracts on the microbiological activity of S. mutans. Common variables were identified to consolidate the data. Authors of this review independently screened search results, extracted data, and assessed the risk of bias.

Results

Of the 420 studies identified from the different databases, 22 publications were finally selected for review. The risk of bias was low in 13 articles and moderate in 9. The studies analyzed in this review revealed that cranberry extract has an inhibitory effect on the bacterial growth of S. mutans in ranges from 0.5 mg/mL to 25 mg/mL, and GSE exerts a similar effect from 0.5 mg/mL to 250 mg/mL. Additionally, the extracts or their fractions showed reduced biofilm formation capacity, decreased polymicrobial biofilm biomass, deregulation of glycosyltransferases (Gtf) B and C expression, and buffering of pH drop. In addition to adequate antioxidant activity related to polyphenol content.

Conclusions

The overall results showed that the extracts of cranberry and grape seed were effective in reducing the virulence factors of the oral pathogen. According to the data, proanthocyanidins are the active components in cranberry and grape seed that effectively resist S. mutans. They can inhibit the formation of insoluble polysaccharides in the extracellular matrix and prevent glycan-mediated adhesion, cohesion, and aggregation of the proteins in S. mutans. This suggests that these natural extracts could play an important role in the prevention of cariogenic bacterial colonization, as well as induce a decrease in their microbiological activity.
Healthcare professional students’ skills in sexual health communication and history taking: inter-rater reliability of standardized patients and faculty ratings in dar es Salaam, tanzania- a cross-sectional study
Authors: Lukumay Gift G. , Mushy Stella Emmanuel , Mgopa Lucy R. , Mkoka Dickson Ally , Massae Agnes F. , Mwakawanga Dorkasi L. , Rosser B. R. Simon , Kohli Nidhi , Rohloff Corissa T. , Ross Michael W. , Trent Maria
Published: June 2024

Background

Low- and middle-income countries face a disproportionate impact of sexual health problems compared to high-income countries. To address this situation proper interpersonal communication skills are essential for clinician to gather necessary information during medical history-taking related to sexual health. This study aimed to evaluate the interrater reliability of ratings on sexual health-related interpersonal communication and medical history-taking between SPs and trained HCP faculty for health care professional students.

Methods

We conducted a cross-sectional comparative study to evaluate the interrater reliability of ratings for sexual health-related interpersonal communication and medical history-taking. The data were collected from medical and nursing students at Muhimbili University of Health and Allied Sciences, who interviewed 12 Standardized Patients (SPs) presenting with sexual health issues. The video-recorded interviews rated by SPs, were compared to the one rated by 5 trained Health Care Professional (HCP) faculty members. Inter-rater reliability was evaluated using percent agreement (PA) and kappa statistics (κ).

Results

A total of 412 students (mean age 24) were enrolled in the study to conduct interviews with two SPs presenting with sexual health concerns. For interpersonal communication (IC), the overall median agreement between raters was slight (κ2 0.0095; PA 48.9%) while the overall median agreement for medical sexual history-taking was deemed fair (κ2 0.139; PA 75.02%).

Conclusion

The use of SPs for training and evaluating medical and nursing students in Tanzania is feasible only if they undergo proper training and have sufficient time for practice sessions, along with providing feedback to the students.
Development of a web-based patient decision aid for myopia laser correction method
Authors: Aghdam Hanieh Delshad , Zarei Fatemeh , Mohammadi Seyed Farzad
Published: June 2024

Background

In the context of healthcare centered on the patient, Patient Decision Aids (PtDAs) acts as an essential instrument, promoting shared decision-making (SDM). Considering the prevalent occurrence of myopia, the objective of this study is to furnish exhaustive and easily comprehensible information to assist patients in making well-informed decisions about their options for myopia laser correction.

Method

The research team developed a decision guide for myopia patients considering laser correction, aiming to facilitate informed decisions. The study followed the first four stages of the IPDAS process model: “scope/scoping,” “design,” “prototype development,” and “alpha testing.” Ten semi-structured interviews with patients (n = 6) and corneal specialist ophthalmologists (n = 4) were conducted to understand the challenges in selecting a laser correction method. Online meetings with 4 corneal specialists were held to discuss challenging cases. A comparison table of harms and benefits was created. The initial prototype was developed and uploaded on the internet portal. User feedback on software and text aspects was incorporated into the final web software, which was reviewed by a health education expert for user-friendliness and effectiveness.

Result

Educational needs assessment revealed concerns such as pain, daily life activities, return to work, the potential need for glasses (‘number return’), eye prescription stability, and possible complications. These shaped the decision aid tool’s content. Expert consensus was achieved in several areas, with some items added or extended. In areas lacking consensus, comments were added for clarity. Five clients assessed the web app (PDAIN), rating it 46/50 in user-centricity, 47/50 in usability, and 45/50 in accuracy and reliability, totaling 138/150. Post-piloting, software errors were documented and rectified. During the trial phase, five myopic users interacted with the software, leading to modifications. User feedback indicated the tool effectively enhanced understanding and influenced decision-making.

Conclusion

PDAIN, serves as a facilitative tool in the process of selecting a corneal laser correction method for myopic patients. It enabling Nearsighted patients to make informed decisions.
A quality improvement study on how a simulation model can help decision making on organization of ICU wards
Authors: Sent Danielle , van der Meulen Delanie M. , Alban Andres , Chick Stephen E. , Wissink Ilse J.A. , Vlaar Alexander P.J. , Dongelmans Dave A.
Published: June 2024

Background

Intensive Care Unit (ICU) capacity management is essential to provide high-quality healthcare for critically ill patients. Yet, consensus on the most favorable ICU design is lacking, especially whether ICUs should deliver dedicated or non-dedicated care. The decision for dedicated or non-dedicated ICU design considers a trade-off in the degree of specialization for individual patient care and efficient use of resources for society. We aim to share insights of a model simulating capacity effects for different ICU designs. Upon request, this simulation model is available for other ICUs.

Methods

A discrete event simulation model was developed and used, to study the hypothetical performance of a large University Hospital ICU on occupancy, rejection, and rescheduling rates for a dedicated and non-dedicated ICU design in four different scenarios. These scenarios either simulate the base-case situation of the local ICU, varying bed capacity levels, potential effects of reduced length of stay for a dedicated design and unexpected increased inflow of unplanned patients.

Results

The simulation model provided insights to foresee effects of capacity choices that should be made. The non-dedicated ICU design outperformed the dedicated ICU design in terms of efficient use of scarce resources.

Conclusions

The choice to use dedicated ICUs does not only affect the clinical outcome, but also rejection- rescheduling and occupancy rates. Our analysis of a large university hospital demonstrates how such a model can support decision making on ICU design, in conjunction with other operation characteristics such as staffing and quality management.
Uncovering essential anesthetics-induced exosomal miRNAs related to hepatocellular carcinoma progression: a bioinformatic investigation
Authors: Huang Ning , Fang Jie , Du Fang , Zhou Jichuan , Li Yuxin , Zhang Xiaoguang
Published: June 2024

Background

Anesthetic drugs may alter exosomal microRNA (miRNA) contents and mediate cancer progression and tumor microenvironment remodeling. Our study aims to explore how the anesthetics (sevoflurane and propofol) impact the miRNA makeup within exosomes in hepatocellular carcinoma (HCC), alongside the interconnected signaling pathways linked to the tumor immune microenvironment.

Methods

In this prospective study, we collected plasma exosomes from two groups of HCC patients (n = 5 each) treated with either propofol or sevoflurane, both before anesthesia and after hepatectomy. Exosomal miRNA profiles were assessed using next-generation sequencing (NGS). Furthermore, the expression data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) was used to pinpoint the differentially expressed exosomal miRNAs (DEmiRNAs) attributed to the influence of propofol or sevoflurane in the context of HCC. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to dissect the signaling pathways and biological activities associated with the identified DEmiRNAs and their corresponding target genes.

Results

A total of 35 distinct DEmiRNAs were exclusively regulated by either propofol (n = 9) or sevoflurane (n = 26). Through TCGA-LIHC database analysis, 8 DEmiRNAs were associated with HCC. These included propofol-triggered miR-452-5p and let-7c-5p, as well as sevoflurane-induced miR-24-1-5p, miR-122-5p, miR-200a-3p, miR-4686, miR-214-3p, and miR-511-5p. Analyses revealed that among these 8 DEmiRNAs, the upregulation of miR-24-1-5p consistently demonstrated a significant association with lower histological grades (p < 0.0001), early-stage tumors (p < 0.05) and higher survival (p = 0.029). Further analyses using GSEA and GSVA indicated that miR-24-1-5p, along with its target genes, were involved in governing the tumor immune microenvironment and potentially inhibiting tumor progression in HCC.

Conclusions

This study provided bioinformatics evidence suggesting that sevoflurane-induced plasma exosomal miRNAs may have a potential impact on the immune microenvironment of HCC. These findings established a foundation for future research into mechanistic outcomes in cancer patients.
Ethanologenic fermentation by Parageobacillus thermoglucosidasius with continuous hot microbubble gas-stripping
Authors: Calverley Joseph , Ibenegbu Christopher , Hussein-Sheik Abdulkadir , Hemaka Bandulasena H. C. , Leak David J.
Published: June 2024

The increased use of biofuels in place of fossil fuels is one strategy to support the transition to net-zero carbon emissions, particularly in transport applications. However, expansion of the use of 1st generation crops as feedstocks is unsustainable due to the conflict with food use. The use of the lignocellulosic fractions from plants and/or co-products from food production including food wastes could satisfy the demand for biofuels without affecting the use of land and the availability of food, but organisms which can readily ferment all the carbohydrates present in these feedstocks often suffer from more severe bioethanol inhibition effects than yeast. This paper demonstrates the potential of hot gas microbubbles to strip ethanol from a thermophilic fermentation process using Parageobacillus thermoglucosidasius TM333, thereby reducing product inhibition and allowing production to continue beyond the nominal toxic ethanol concentrations of ≤ 2% v/v. Using an experimental rig in which cells were grown in fed-batch cultures on sugars derived from waste bread, and the broth continuously cycled through a purpose-built microbubble stripping unit, it was shown that non/low-inhibitory dissolved ethanol concentrations could be maintained throughout, despite reaching productivities equivalent to 4.7% v/v dissolved ethanol. Ethanol recovered in the condensate was at a concentration appropriate for dewatering to be cost effective and not prohibitively energy intensive. This suggests that hot microbubble stripping could be a valuable technology for the continuous production of bioethanol from fermentation processes which suffer from product inhibition before reaching economically viable titres, which is typical of most thermophilic ethanologenic bacteria.
A production platform for disulfide-bonded peptides in the periplasm of Escherichia coli
Authors: Gibisch Martin , Müller Matthias , Tauer Christopher , Albrecht Bernd , Hahn Rainer , Cserjan-Puschmann Monika , Striedner Gerald
Published: June 2024

Background

Recombinant peptide production in Escherichia coli provides a sustainable alternative to environmentally harmful and size-limited chemical synthesis. However, in-vivo production of disulfide-bonded peptides at high yields remains challenging, due to degradation by host proteases/peptidases and the necessity of translocation into the periplasmic space for disulfide bond formation.

Results

In this study, we established an expression system for efficient and soluble production of disulfide-bonded peptides in the periplasm of E. coli. We chose model peptides with varying complexity (size, structure, number of disulfide bonds), namely parathyroid hormone 1–84, somatostatin 1–28, plectasin, and bovine pancreatic trypsin inhibitor (aprotinin). All peptides were expressed without and with the N-terminal, low molecular weight CASPON™ tag (4.1 kDa), with the expression cassette being integrated into the host genome. During BioLector™ cultivations at microliter scale, we found that most of our model peptides can only be sufficiently expressed in combination with the CASPON™ tag, otherwise expression was only weak or undetectable on SDS-PAGE. Undesired degradation by host proteases/peptidases was evident even with the CASPON™ tag. Therefore, we investigated whether degradation happened before or after translocation by expressing the peptides in combination with either a co- or post-translational signal sequence. Our results suggest that degradation predominantly happened after the translocation, as degradation fragments appeared to be identical independent of the signal sequence, and expression was not enhanced with the co-translational signal sequence. Lastly, we expressed all CASPON™-tagged peptides in two industry-relevant host strains during C-limited fed-batch cultivations in bioreactors. We found that the process performance was highly dependent on the peptide-host-combination. The titers that were reached varied between 0.6–2.6 g L−1, and exceeded previously published data in E. coli. Moreover, all peptides were shown by mass spectrometry to be expressed to completion, including full formation of disulfide bonds.

Conclusion

In this work, we demonstrated the potential of the CASPON™ technology as a highly efficient platform for the production of soluble peptides in the periplasm of E. coli. The titers we show here are unprecedented whenever parathyroid hormone, somatostatin, plectasin or bovine pancreatic trypsin inhibitor were produced in E. coli, thus making our proposed upstream platform favorable over previously published approaches and chemical synthesis.
Defining the next generation of severe malaria treatment: a target product profile
Authors: Achan Jane , Barry Aïssata , Leroy Didier , Kamara George , Duparc Stephan , Kaszubska Wiweka , Gandhi Preetam , Buffet Bénédicte , Tshilab Patrick , Ogutu Bernhards , Taylor Terrie , Krishna Sanjeev , Richardson Naomi , Ramachandruni Hanu , Rietveld Hans
Published: June 2024

Background

Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies.

Target product profile

Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings.

Conclusion

Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease.
The impact of an innovative payment method on medical expenditure, efficiency, and quality for inpatients with different types of medical insurance: evidence from a pilot city, China
Authors: Lin Kunhe , Li Yunfei , Yao Yifan , Xiong Yingbei , Xiang Li
Published: June 2024

Background

Since 2020, China has implemented an innovative payment method called Diagnosis-Intervention Packet (DIP) in 71 cities nationwide. This study aims to assess the impact of DIP on medical expenditure, efficiency, and quality for inpatients covered by the Urban Employee Basic Medical Insurance (UEBMI) and Urban and Rural Residents Basic Medical Insurance (URRBMI). It seeks to explore whether there are differences in these effects among inpatients of the two insurance types, thereby further understanding its implications for health equity.

Materials and methods

We conducted interrupted time series analyses on outcome variables reflecting medical expenditure, efficiency, and quality for both UEBMI and URRBMI inpatients, based on a dataset comprising 621,125 inpatient reimbursement records spanning from June 2019 to June 2023 in City A. This dataset included 110,656 records for UEBMI inpatients and 510,469 records for URRBMI inpatients.

Results

After the reform, the average expenditure per hospital admission for UEBMI inpatients did not significantly differ but continued to follow an upward pattern. In contrast, for URRBMI inpatients, the trend shifted from increasing before the reform to decreasing after the reform, with a decline of 0.5%. The average length of stay for UEBMI showed no significant changes after the reform, whereas there was a noticeable downward trend in the average length of stay for URRBMI. The out-of-pocket expenditure (OOP) per hospital admission, 7-day all-cause readmission rate and 30-day all-cause readmission rate for both UEBMI and URRBMI inpatients showed a downward trend after the reform.

Conclusion

The DIP reform implemented different upper limits on budgets based on the type of medical insurance, leading to varying post-treatment prices for UEBMI and URRBMI inpatients within the same DIP group. After the DIP reform, the average expenditure per hospital admission and the average length of stay remained unchanged for UEBMI inpatients, whereas URRBMI inpatients experienced a decrease. This trend has sparked concerns about hospitals potentially favoring UEBMI inpatients. Encouragingly, both UEBMI and URRBMI inpatients have seen positive outcomes in terms of alleviating patient financial burdens and enhancing the quality of care.
S1PR3 inhibition protects against LPS-induced ARDS by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation
Authors: Peng Junnan , Tang Rui , He Jing , Yu Qian , Wang Daoxin , Qi Di
Published: June 2024

Background

Inflammation and endothelial barrier dysfunction are the major pathophysiological changes in acute respiratory distress syndrome (ARDS). Sphingosine-1-phosphate receptor 3 (S1PR3), a G protein-coupled receptor, has been found to mediate inflammation and endothelial cell (EC) integrity. However, the function of S1PR3 in ARDS has not been fully elucidated.

Methods

We used a murine lipopolysaccharide (LPS)-induced ARDS model and an LPS- stimulated ECs model to investigate the role of S1PR3 in anti-inflammatory effects and endothelial barrier protection during ARDS.

Results

We found that S1PR3 expression was increased in the lung tissues of mice with LPS-induced ARDS. TY-52156, a selective S1PR3 inhibitor, effectively attenuated LPS-induced inflammation by suppressing the expression of proinflammatory cytokines and restored the endothelial barrier by repairing adherens junctions and reducing vascular leakage. S1PR3 inhibition was achieved by an adeno-associated virus in vivo and a small interfering RNA in vitro. Both the in vivo and in vitro studies demonstrated that pharmacological or genetic inhibition of S1PR3 protected against ARDS by inhibiting the NF-κB pathway and improving mitochondrial oxidative phosphorylation.

Conclusions

S1PR3 inhibition protects against LPS-induced ARDS via suppression of pulmonary inflammation and promotion of the endothelial barrier by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation, indicating that S1PR3 is a potential therapeutic target for ARDS.
The prevalence and genotype distribution of human papillomavirus in central Fujian Province during the COVID-19 pandemic
Authors: Lin Boxi , Zhang Fu , Liu Fang , Huang Lihua , Xie Shanzhen , Lin Qing , Liu Jilai
Published: June 2024

Background

Global human activities were significantly impacted by the emergence of the coronavirus disease 2019 (COVID-19) pandemic caused by the 2019 novel coronavirus. This study aimed to investigate the prevalence and genotype distribution of HPV infection in Central Fujian Province during the pandemic.

Methods

Cervical samples were collected from 21,612 outpatients and 12,664 females who underwent physical examinations and HPV screening at the People’s Hospital of Fujian Province in Fuzhou from April 2020 to April 2023. HPV detection and genotyping were conducted using PCR hybridization.

Results

The overall HPV infection rate was 16.1% during the COVID-19 pandemic, with the outpatient group exhibiting a greater infection rate (19.0%) than did the healthy group (12.3%). The top five high-risk HPV (HR-HPV) genotypes in both groups were HPV52, HPV53, HPV58, HPV16, and HPV51. Additionally, HPV81 and HPV43 were the two most common low-risk HPV (LR-HPV) genotypes in the patient group, while HPV81 and HPV42 were the two most common LR-HPV genotypes in the healthy group. The highest prevalence of HPV infection was observed in individuals aged ≤ 24 years (28.4%, 95% CI 25.9–30.9), followed by those aged ≥ 55 years (23.6%, 95% CI 21.6–24.7) and other age groups. The prevalence decreased from 23.0% (95% CI 22.4–23.7) in 2018–2019 to 13.8% (95% CI 12.0-15.5) in 2023.

Conclusion

This study provides valuable insights into the prevalence and genotypes of HPV infection in the female population of Central Fujian Province from 2020 to 2023. The findings indicate that the prevalence of HPV infection in Central Fujian Province remains relatively low compared to the national average. Furthermore, the prevalence of HPV decreased during the COVID-19 pandemic; however, as the pandemic waned, there was potential for an increase in HPV infection rates. Therefore, it is crucial to strengthen HPV screening and vaccination strategies to prevent the potential spread of HPV.
Dendritic spine head diameter is reduced in the prefrontal cortex of progranulin haploinsufficient mice
Authors: Cook Anna K. , Greathouse Kelsey M. , Manuel Phaedra N. , Cooper Noelle H. , Eberhardt Juliana M. , Freeman Cameron D. , Weber Audrey J. , Herskowitz Jeremy H. , Arrant Andrew E.
Published: June 2024

Loss-of-function mutations in the progranulin (GRN) gene are an autosomal dominant cause of Frontotemporal Dementia (FTD). These mutations typically result in haploinsufficiency of the progranulin protein. Grn+/– mice provide a model for progranulin haploinsufficiency and develop FTD-like behavioral abnormalities by 9–10 months of age. In previous work, we demonstrated that Grn+/– mice develop a low dominance phenotype in the tube test that is associated with reduced dendritic arborization of layer II/III pyramidal neurons in the prelimbic region of the medial prefrontal cortex (mPFC), a region key for social dominance behavior in the tube test assay. In this study, we investigated whether progranulin haploinsufficiency induced changes in dendritic spine density and morphology. Individual layer II/III pyramidal neurons in the prelimbic mPFC of 9–10 month old wild-type or Grn+/– mice were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and 3D reconstruction for morphometry analysis. Dendritic spine density in Grn+/– mice was comparable to wild-type littermates, but the apical dendrites in Grn+/– mice had a shift in the proportion of spine types, with fewer stubby spines and more thin spines. Additionally, apical dendrites of Grn+/– mice had longer spines and smaller thin spine head diameter in comparison to wild-type littermates. These changes in spine morphology may contribute to altered circuit-level activity and social dominance deficits in Grn+/– mice.
TDP43 interacts with MLH1 and MSH6 proteins in a DNA damage-inducible manner
Authors: Provasek Vincent E. , Kodavati Manohar , Kim Brandon , Mitra Joy , Hegde Muralidhar L.
Published: June 2024

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the motor neuron. One aspect of the neuropathology involved in ALS includes increased genomic damage and impaired DNA repair capability. The TAR-DNA binding protein 43 (TDP43) has been associated with both sporadic and familial forms of ALS, and is typically observed as cytosolic mislocalization of protein aggregates, termed TDP43 proteinopathy. TDP43 is a ubiquitous RNA/DNA binding protein with functional implications in a wide range of disease processes, including the repair of DNA double-strand breaks (DSBs). While TDP43 is widely known to regulate RNA metabolism, our lab has reported it also functions directly at the protein level to facilitate DNA repair. Here, we show that the TDP43 protein interacts with DNA mismatch repair (MMR) proteins MLH1 and MSH6 in a DNA damage-inducible manner. We utilized differentiated SH-SY5Y neuronal cultures to identify this inducible relationship using complementary approaches of proximity ligation assay (PLA) and co-immunoprecipitation (CoIP) assay. We observed that signals of TDP43 interaction with MLH1 and MSH6 increased significantly following a 2 h treatment of 10 μM methylmethanesulfonate (MMS), a DNA alkylating agent used to induce MMR repair. Likewise, we observed this effect was abolished in cell lines treated with siRNA directed against TDP43. Finally, we demonstrated these protein interactions were significantly increased in lumbar spinal cord samples of ALS-affected patients compared to age-matched controls. These results will inform our future studies to understand the mechanisms and consequences of this TDP43-MMR interaction in the context of ALS-affected neurons.
Growth behavior and mRNA expression profiling during growth of IPEC-J2 cells
Authors: Binder A. Ronja D. , Mussack Veronika , Kirchner Benedikt , Pfaffl Michael W.
Published: June 2024

Objective

The IPEC-J2 cell line is used as an in vitro small intestine model for swine, but it is also used as a model for the human intestine, presenting a relatively unique setting. By combining electric cell-substrate impedance sensing, with next-generation-sequencing technology, we showed that mRNA gene expression profiles and related pathways can depend on the growth phase of IPEC-J2 cells. Our investigative approach welcomes scientists to reproduce or modify our protocols and endorses putting their gene expression data in the context of the respective growth phase of the cells.

Results

Three time points are presented: (TP1) 1 h after medium change (= 6 h after seeding of cells), (TP2) the time point of the first derivative maximum of the cell growth curve, and a third point at the beginning of the plateau phase (TP3). Significantly outstanding at TP1 compared to TP2 was upregulated PLEKHN1, further FOSB and DEGS2 were significantly downregulated at TP2 compared to TP3. Any provided data can be used to improve next-generation experiments with IPEC-J2 cells.
Low testosterone levels relate to poorer cognitive function in women in an APOE-ε4-dependant manner
Authors: Dratva Melanie A. , Banks Sarah J. , Panizzon Matthew S. , Galasko Douglas , Sundermann Erin E. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2024

Background

Past research suggests that low testosterone levels relate to poorer cognitive function and higher Alzheimer’s disease (AD) risk; however, these findings are inconsistent and are mostly derived from male samples, despite similar age-related testosterone decline in females. Both animal and human studies demonstrate that testosterone’s effects on brain health may be moderated by apolipoprotein E ε4 allele (APOE-ε4) carrier status, which may explain some previous inconsistencies. We examined how testosterone relates to cognitive function in older women versus men across healthy aging and the AD continuum and the moderating role of APOE-ε4 genotype.

Methods

Five hundred and sixty one participants aged 55–90 (155 cognitively normal (CN), 294 mild cognitive impairment (MCI), 112 AD dementia) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), who had baseline cognitive and plasma testosterone data, as measured by the Rules Based Medicine Human DiscoveryMAP Panel were included. There were 213 females and 348 males (self-reported sex assigned at birth), and 52% of the overall sample were APOE-ε4 carriers. We tested the relationship of plasma testosterone levels and its interaction with APOE-ε4 status on clinical diagnostic group (CN vs. MCI vs. AD), global, and domain-specific cognitive performance using ANOVAs and linear regression models in sex-stratified samples. Cognitive domains included verbal memory, executive function, processing speed, and language.

Results

We did not observe a significant difference in testosterone levels between clinical diagnostic groups in either sex, regrardless of APOE-ε4 status. Across clinical diagnostic group, we found a significant testosterone by APOE-ε4 interaction in females, such that lower testosterone levels related to worse global cognition, processing speed, and verbal memory in APOE-ε4 carriers only. We did not find that testosterone, nor its interaction with APOE-ε4, related to cognitive outcomes in males.

Conclusions

Findings suggest that low testosterone levels in older female APOE-ε4 carriers across the aging-MCI-AD continuum may have deleterious, domain-specific effects on cognitive performance. Although future studies including additional sex hormones and longitudinal cognitive trajectories are needed, our results highlight the importance of including both sexes and considering APOE-ε4 carrier status when examining testosterone’s role in cognitive health.
Chemical screen in zebrafish lateral line identified compounds that ameliorate neomycin-induced ototoxicity by inhibiting ferroptosis pathway
Authors: Fan Yipu , Zhang Yihan , Qin Dajiang , Shu Xiaodong
Published: June 2024

Background

Ototoxicity is a major side effect of many broadly used aminoglycoside antibiotics (AGs) and no FDA-approved otoprotective drug is available currently. The zebrafish has recently become a valuable model to investigate AG-induced hair cell toxicity and an expanding list of otoprotective compounds that block the uptake of AGs have been identified from zebrafish-based screening; however, it remains to be established whether inhibiting intracellular cell death pathway(s) constitutes an effective strategy to protect against AG-induced ototoxicity.

Results

We used the zebrafish model as well as in vitro cell-based assays to investigate AG-induced cell death and found that ferroptosis is the dominant type of cell death induced by neomycin. Neomycin stimulates lipid reactive oxygen species (ROS) accumulation through mitochondrial pathway and blocking mitochondrial ferroptosis pathway effectively protects neomycin-induced cell death. We screened an alkaloid natural compound library and identified seven small compounds that protect neomycin-induced ototoxicity by targeting ferroptosis pathway: six of them are radical-trapping agents (RTAs) while the other one (ellipticine) regulates intracellular iron homeostasis, which is essential for the generation of lipid ROS to stimulate ferroptosis.

Conclusions

Our study demonstrates that blocking intracellular ferroptosis pathway is an alternative strategy to ameliorate neomycin-induced ototoxicity and provides multiple hit compounds for further otoprotective drug development.
Bounds for novel extended beta and hypergeometric functions and related results
Authors: Parmar Rakesh K. , Pogány Tibor K.
Published: June 2024

We introduce a new unified extension of the integral form of Euler’s beta function with a MacDonald function in the integrand and establish functional upper bounds for it. We use this definition to extend as well the Gaussian and Kummer’s confluent hypergeometric functions, for which we provide bounding inequalities. Moreover, we use our extension of the beta function to define a new probability distribution, for which we establish raw moments and moment inequalities and, as by-products, Turán inequalities for the initially defined extended beta function.
Anticancer activity of peptide W-0803 derived from Anoplophoa glabripennis
Authors: Yeom Jae Ho , Lee Jin-Woo , Hong Seung Myun , Lee Deok Jae , Park Dong Choon , Chung Namhyun
Published: June 2024

Natural compounds are known as a resource of anti-cancer agents. Anti-cancer capacity toward human epithelial lung cancer cell lines (A549, H460) was examined with and without treatment of trypsin on the extract of Anoplophora glabripennis. IC50 values without trypsin treatment were about 21.3 and 25.0 μg/mL for H460 and A549, respectively. When the extract was treated with trypsin, the IC50 values were 16.0 and 15.6 μg/mL for H460 and A549, respectively, indicating that the trypsin treatment increased the anti-cancer capacity. Because trypsin treatment increased the capacity, the extract was treated with trypsin to isolate the peptide W-0803 which has lysin (K) in C-terminal and α-helix structures. With treatment of W-0803, the cell viability decreased dose-dependently for H460 and A549 cells. Apoptosis analysis showed that the cell death with the treatment of peptide W-0803 was mainly by apoptosis. The wound-healing assay also showed that the peptide W-0803 has an inhibitory capability on cell migration of H460 and A549 cells. All these results suggest that the peptide W-0803 is an anti-cancer agent for lung cancer cell treatment.