bluuebunny/crossref_metadata_2025 huggingface dataset:
Perinatal outcomes and sinopharm BBIBP-CorV vaccination during pregnancy
Authors: Hatami Donya , Habibelahi Abbas , Changizi Nasrin , Heidarzadeh Mohammad , Nojomi Marzieh , Rast Moein , Ansari Kiarash , Tehrani‐Banihashemi Arash
Published: March 2024

Background

After the outbreak of COVID-19, a huge part of the health care services was dedicated to preventing and treating this disease. In case of COVID-19 infection, severe COVID-19 is reported more in pregnant individuals. Afterward, Vaccination against SARS-CoV-2 became a hot topic due to known effects in preventing severe COVID-19 during pregnancy.

Vaccination of pregnant individuals started in August 2021 with the Sinopharm vaccine in Iran. The aim of current study was to determine the incidence of perinatal outcomes in women who were vaccinated during pregnancy.

Method

This retrospective cohort study included 129,488 singleton births from March 21, 2021, until March 21, 2022, in Tehran, Iran.

The data was obtained from the Iranian Maternal and Neonatal (IMaN) Network and the Maternal Vaccination Registry.

Adverse perinatal outcomes investigated in this study include preterm birth, extremely preterm birth, low birth weight, very low birth weight, intrauterine growth restriction, stillbirth, neonatal intensive care unit admission, congenital anomaly, neonatal death and low 5-minute Apgar score. The risk of all perinatal outcomes was evaluated using multiple logistic regression. The analysis was done using STATA version 14.

Results

Of all 129,488 singleton births included in this study, 17,485 (13.5%) were vaccinated against SARS-CoV-2 (all with Sinopharm (BBIBP-CorV)). The exposure to the Sinopharm vaccine during pregnancy caused a significant decrease in the incidence of preterm birth (P =0.006, OR=0.91 [95% CI, 0.85 to 0.97]), extremely preterm birth (P =<0.001,OR=0.55 [95% CI, 0.45 to 0.66]), and stillbirth (P =<0.001, OR=0.60 [95% CI, 0.47 to 0.76]). Exposure to vaccination during the first trimester was associated with an increased risk of preterm birth (P =0.01, OR=1.27 [95% CI, 1.04 to 1.55])

Maternal vaccination during pregnancy was not associated with an increased risk of other adverse perinatal outcomes included in this study.

Conclusion

The finding of this population-based study indicated no adverse pregnancy outcome due to vaccination with the Sinopharm vaccine during the second and third trimesters of pregnancy. Overall risk of adverse pregnancy outcomes were lower in the vaccinated individuals compared to the unvaccinated group. Also, vaccination during the first trimester was associated with an increased risk of preterm birth.
Using online search activity for earlier detection of gynaecological malignancy
Authors: Barcroft Jennifer F. , Yom-Tov Elad , Lampos Vasileios , Ellis Laura Burney , Guzman David , Ponce-López Víctor , Bourne Tom , Cox Ingemar J. , Saso Srdjan
Published: March 2024

Background

Ovarian cancer is the most lethal and endometrial cancer the most common gynaecological cancer in the UK, yet neither have a screening program in place to facilitate early disease detection. The aim is to evaluate whether online search data can be used to differentiate between individuals with malignant and benign gynaecological diagnoses.

Methods

This is a prospective cohort study evaluating online search data in symptomatic individuals (Google user) referred from primary care (GP) with a suspected cancer to a London Hospital (UK) between December 2020 and June 2022. Informed written consent was obtained and online search data was extracted via Google takeout and anonymised. A health filter was applied to extract health-related terms for 24 months prior to GP referral. A predictive model (outcome: malignancy) was developed using (1) search queries (terms model) and (2) categorised search queries (categories model). Area under the ROC curve (AUC) was used to evaluate model performance. 844 women were approached, 652 were eligible to participate and 392 were recruited. Of those recruited, 108 did not complete enrollment, 12 withdrew and 37 were excluded as they did not track Google searches or had an empty search history, leaving a cohort of 235.

Results

The cohort had a median age of 53 years old (range 20–81) and a malignancy rate of 26.0%. There was a difference in online search data between those with a benign and malignant diagnosis, noted as early as 360 days in advance of GP referral, when search queries were used directly, but only 60 days in advance, when queries were divided into health categories. A model using online search data from patients (n = 153) who performed health-related search and corrected for sample size, achieved its highest sample-corrected AUC of 0.82, 60 days prior to GP referral.

Conclusions

Online search data appears to be different between individuals with malignant and benign gynaecological conditions, with a signal observed in advance of GP referral date. Online search data needs to be evaluated in a larger dataset to determine its value as an early disease detection tool and whether its use leads to improved clinical outcomes.
A dynamic approach to support outbreak management using reinforcement learning and semi-connected SEIQR models
Authors: Kao Yamin , Chu Po-Jui , Chou Pai-Chien , Chen Chien-Chang
Published: March 2024

Background

Containment measures slowed the spread of COVID-19 but led to a global economic crisis. We establish a reinforcement learning (RL) algorithm that balances disease control and economic activities.

Methods

To train the RL agent, we design an RL environment with 4 semi-connected regions to represent the COVID-19 epidemic in Tokyo, Osaka, Okinawa, and Hokkaido, Japan. Every region is governed by a Susceptible-Exposed-Infected-Quarantined-Removed (SEIQR) model and has a transport hub to connect with other regions. The allocation of the synthetic population and inter-regional traveling is determined by population-weighted density. The agent learns the best policy from interacting with the RL environment, which involves obtaining daily observations, performing actions on individual movement and screening, and receiving feedback from the reward function. After training, we implement the agent into RL environments describing the actual epidemic waves of the four regions to observe the agent’s performance.

Results

For all epidemic waves covered by our study, the trained agent reduces the peak number of infectious cases and shortens the epidemics (from 165 to 35 cases and 148 to 131 days for the 5th wave). The agent is generally strict on screening but easy on movement, except for Okinawa, where the agent is easy on both actions. Action timing analyses indicate that restriction on movement is elevated when the number of exposed or infectious cases remains high or infectious cases increase rapidly, and stringency on screening is eased when the number of exposed or infectious cases drops quickly or to a regional low. For Okinawa, action on screening is tightened when the number of exposed or infectious cases increases rapidly.

Conclusions

Our experiments exhibit the potential of the RL in assisting policy-making and how the semi-connected SEIQR models establish an interactive environment for imitating cross-regional human flows.
3 Months without the car in Bielefeld, Germany– a mixed-method study exploring individual motivation to participate in a municipal intervention
Authors: Nowak Anna Christina , Lopez Lumbi Susanne , Mc Call Timothy
Published: March 2024

Background

Climate change is a major public health issue worldwide. To achieve climate targets and reduce morbidity, a paradigm shift in individual behavior e.g., in mobility, is needed. Municipal interventions can motivate individuals to engage in climate-friendly behavior through different psychological mechanisms. In order for successful interventions, it is necessary to gain better insight from study participants and their reasons for participating in mobility projects (e.g., motivational aspects).

Materials and methods

A mixed-methods design was used to evaluate reasons and characteristics of people for participating in an municipal mobility intervention. The quantitative sub-study assesses socioeconomic characteristics, environmental awareness and perceived stress. The qualitative sub-study explores motivation for participation and change, perspectives on car replacement and reasons for car use.

Results

Results show that participants (n = 42) are rather high educated and show medium environmental awareness. Participants of the qualitative study part (n = 15) were motiviated to reduce car use already before the intervention and used the intervention as starting point or trial phase.

Conclusions

Urban intervention projects with fitted recruitment strategies and better insights from study participants with the aim to motivate individuals to engage in climate-friendly behavior can help to strengthen sustainability and public health.
Effect of health rights accessibility on the urban integration of minority rural migrants in China: a cross-sectional study
Authors: Zhao Qingjun , Wu Guosong , Wang Hanrui
Published: March 2024

Background

Accessing health rights is an integral component of people’s aspirations for a better life. Existing discussions and evaluations regarding the accessibility of health rights for minority rural migrants are insufficient. In comparison to objective health conditions, inequalities in health rights lead to chronic and long-term depletion of human capital among minority rural migrants. This study aimed to assess the overall impact, heterogeneity effects, and mechanisms of health rights accessibility on the urban integration of minority rural migrants.

Methods

Based on the 2017 China Migrants Dynamic Survey Data (CMDS), this study employs OLS models, 2SLS models, conditional mixed process (CMP) methods, and omitted variable tests to estimate the impact of health rights accessibility on the urban integration of minority rural migrants. Additionally, from the perspectives of migration scope and illness experience, this study explored the heterogeneity in the relationship between health rights accessibility and urban integration. Finally, using the Karlson–Holm–Breen (KHB) model, this study dissects the mechanisms through which health rights accessibility influences the urban integration of minority rural migrants.

Results

Health rights accessibility significantly enhances the urban integration of minority rural migrants. Moreover, compared to minority rural migrants who move across provinces and who have no history of illness, those who migrate within the same province and who have experienced illness are more sensitive to the positive impact of health rights accessibility. However, the enhancing effect of health rights accessibility does not significantly differ between the new and old generations of minority rural migrants. Furthermore, health rights accessibility can indirectly improve the urban integration of minority rural migrants by elevating health levels, improving health habits, and reinforcing health behaviors. Among these, the indirect effects mediated by health habits are more pronounced.

Conclusion

The research conclusions underscore the issue of health accessibility and urban integration among minority rural migrants, providing a reexamination and clarification of the policy effects of health rights in promoting the urban integration of minority rural migrants. Relevant policy design should commence with improving the health rights of minority rural migrants, enhancing their health integration capabilities, and effectively boosting their ability to integrate into urban life.
Prevalence and prognosis of fulminant type 1 diabetes mellitus in The Middle East: a comparative analysis in a 5-year nationwide cohort
Authors: Ata Fateen , Khan Adeel Ahmad , Khamees Ibrahim , AlKodmani Sham , Al-Sadi Anas , Yaseen Khaled Bani , Muthanna Bassam , Godwin Angela , Beer Stephen Frederick , Bashir Mohammed
Published: March 2024

Purpose

To analyze the prevalence and progression of fulminant type 1 diabetes (FT1D) in Qatar.

Methods

This retrospective study analyzed consecutive index- diabetic ketoacidosis (DKA) admissions (2015–2020) among patients with new-onset T1D (NT1D) in Qatar.

Results

Of the 242 patients, 2.5% fulfilled the FT1D diagnostic criteria. FT1D patients were younger (median-age 4-years vs.15-years in classic-T1D). Gender distribution in FT1D was equal, whereas the classic-T1D group showed a female predominance at 57.6% (n = 136). FT1D patients had a mean C-peptide of 0.11 ± 0.09 ng/ml, compared to 0.53 ± 0.45 ng/ml in classic-T1D. FT1D patients had a median length of stay (LOS) of 1 day (1-2.2) and a DKA duration of 11.25 h (11–15). The median (length of stay) LOS and DKA duration in classic-T1D patients were 2.5 days (1-3.9) and 15.4 h (11–23), respectively. The FT1D subset primarily consisted of moderate (83.3%) and severe 916.7%) DKA, whereas classic T1D had 25.4% mild, 60.6% moderate, and 14% severe DKA cases. FT1D was associated with a higher median white cell count (22.3 × 103/uL) at admission compared to classic T1D (10.6 × 103/uL). ICU admission was needed for 66.6% of FT1D patients, compared to 38.1% of classic-T1D patients. None of the patients in the FT1D group had mortality, while two died in the classic-T1D group.

Conclusion

This is the first study establishing the existence of FT1D in ME, which presented distinctively from classic-T1D, exhibiting earlier age onset and higher critical care requirements. However, the clinical outcomes in patients with FT1D seem similar to classic T1D.
L-shaped association between the GA/HbA1c ratio and all-cause mortality in U.S. adults with NAFLD: a cross-sectional study from the NHANES 1999–2004
Authors: Zhang Zhaofu , Wang Hao , Chen Mingyu , Chen Youpeng
Published: March 2024

Objective

It is currently unclear whether there is a relationship between the ratio of glycated albumin to hemoglobin A1c (GA/HbA1c) and mortality in individuals diagnosed with nonalcoholic fatty liver disease (NAFLD). The primary objective of the study was to investigate the relationship between the GA/HbA1c ratio and all-cause mortality in adults with NAFLD in the U.S.

Methods

The investigation included a total of 5,295 individuals aged ≥ 18 years who were diagnosed with NAFLD, these individuals were selected from the National Health and Nutrition Examination Survey conducted between 1999 and 2004. To evaluate the outcomes of death, the researchers relied on National Death Index (NDI) records up to December 31, 2019. To better understand the nonlinear relationship between the GA/HbA1c ratio and mortality among individuals with NAFLD, this study employed both subgroup and sensitivity analyses. Furthermore, Cox proportional hazards models and two-part Cox proportional hazards model were utilized.

Results

The study included a total of 5,295 adult patients with NAFLD in the U.S. During a median follow-up period of 16.9 years, there were 1,471 recorded deaths, including 419 cardiovascular deaths. After accounting for various factors, a higher GA/HbA1c ratio exhibited a positive and nonlinear association with an increased risk of all-cause mortality in patients with NAFLD. Furthermore, the study revealed an L-shaped relationship between the GA/HbA1c ratio and all-cause mortality, with the inflection point occurring at a GA/HbA1c ratio of 2.21. When the GA/HbA1c ratio exceeded 2.21, each 1-unit increase in the ratio was associated with a 33% increase in the adjusted hazard ratio (HR 1.33; 95% CI 1.14, 1.60) for all-cause mortality.

Conclusions

A nonlinear correlation between the ratio of GA to HbA1c and all-cause mortality was observed in U.S. adults with NAFLD. In addition, an elevated GA/HbA1c ratio was linked to an increased risk of all-cause mortality in these patients.
Prenatal exposure to environmental toxins and comprehensive dental findings in a population cohort of children
Authors: Winkler James R. , Dixon Barbara L. , Singh Ishita , Soto Ray , Qiu Yuqing , Zhang Yue , Porucznik Christina A. , Stanford Joseph B.
Published: March 2024

Environmental toxins are known to have many impacts on growth and development in humans, starting in utero. Alterations in amelogenesis, caused by chemical and physical trauma that occur during the antenatal, perinatal and postnatal time periods, may result in developmental defects in deciduous and permanent tooth enamel, as demonstrated in animal studies. These defects can be clinically visible and result in a variety of morphological and functional problems in the dentition. Since enamel does not remodel after formation, it may serve as a permanent record of insults during organ development.

Our primary purpose was to investigate any possible relationship between intrauterine exposure to endocrine disrupting chemicals (phenols and phthalates) and developmental defects in enamel in children, while also accounting for fluoride exposure. Our secondary purpose was to report descriptively on findings from comprehensive dental examinations performed on 356 children that were drawn from the general paediatric population. A cohort of children from the Utah Children’s Project (N = 356) that had full medical exams, comprehensive medical and family histories and available biospecimens were given extraoral and intraoral examinations. They also completed an oral health questionnaire. Standardized intraoral photographs were taken of the teeth and viewed by standardised examiners and the dental observations were recorded for a full inventory of findings, including: tooth morphology, caries, restorations, colorations, attrition, erosion, fractures and hypomineralization. Perinatal maternal urine samples were assessed for the concentration of fluoride, phenols and phthalates, including bisphenol A (BPA).

Pairwise statistical analyses were done to correlate the dental findings with one another and with the presence of environment chemicals found in the urine samples. Hypomineralization was the most common finding (96% of children; 37% of deciduous teeth, 42% of permanent teeth), consistent with molar incisor hypomineralization (MIH) described in other human populations. No consistent correlations were seen between dental findings and the presence of phenols and phthalates in prenatal urine, but the number of samples available for the assessment was limited (n = 35).

In conclusion, we found a high proportion of dental hypomineralization in a population based paediatric cohort, but did not find an association with prenatal exposure to phenols and phthalates.
Hard tissue formation in pulpotomized primary teeth in dogs with nanomaterials MCM-48 and MCM-48/hydroxyapatite: an in vivo animal study
Authors: Talebi Sahar , Nourbakhsh Nosrat , Talebi Ardeshir , Nourbakhsh Amir Abbas , Haghighat Abbas , Manshayi Maziar , Bakhsheshi Hamid Reza , Karimi Razieh , Nazeri Rahman , Mackenzie Kenneth J.D.
Published: March 2024

Background

This animal study sought to evaluate two novel nanomaterials for pulpotomy of primary teeth and assess the short-term pulpal response and hard tissue formation in dogs. The results were compared with mineral trioxide aggregate (MTA).

Methods

This in vivo animal study on dogs evaluated 48 primary premolar teeth of 4 mongrel female dogs the age of 6–8 weeks, randomly divided into four groups (n = 12). The teeth underwent complete pulpotomy under general anesthesia. The pulp tissue was capped with MCM-48, MCM-48/Hydroxyapatite (HA), MTA (positive control), and gutta-percha (negative control), and the teeth were restored with intermediate restorative material (IRM) paste and amalgam. After 4–6 weeks, the teeth were extracted and histologically analyzed to assess the pulpal response to the pulpotomy agent.

Results

The data were analyzed using the Kruskal‒Wallis, Fisher’s exact, Spearman’s, and Mann‒Whitney tests. The four groups were not significantly different regarding the severity of inflammation (P = 0.53), extent of inflammation (P = 0.72), necrosis (P = 0.361), severity of edema (P = 0.52), extent of edema (P = 0.06), or connective tissue formation (P = 0.064). A significant correlation was noted between the severity and extent of inflammation (r = 0.954, P < 0.001). The four groups were significantly different regarding the frequency of bone formation (P = 0.012), extent of connective tissue formation (P = 0.047), severity of congestion (P = 0.02), and extent of congestion (P = 0.01). No bone formation was noted in the gutta-percha group. The type of newly formed bone was not significantly different among the three experimental groups (P = 0.320).

Conclusion

MCM-48 and MCM-48/HA are bioactive nanomaterials that may serve as alternatives for pulpotomy of primary teeth due to their ability to induce hard tissue formation. The MCM-48 and MCM-48/HA mesoporous silica nanomaterials have the potential to induce osteogenesis and tertiary (reparative) dentin formation.
Effects of pubic hair grooming on women’s sexual health: a systematic review and meta-analysis
Authors: Eltobgy Asmaa , Aljabali Ahmed , Farag Ahmed , Elshorbgy Mohammad , Hamed Mona , Hamouda Esraa , Hamouda Heba , Refaey Neveen , Kabeel Marwa , Amro Sarah , Abouheseba Toka , Tarek Mohammed
Published: March 2024

Background

Pubic hair grooming involves the partial or complete removal of pubic hair, and it is a common practice among men and women. Grooming is more prevalent in women, who employ various methods such as shaving, waxing and laser removal. However, it is associated with variable rates of post-grooming adverse outcomes including lacerations and sexually transmitted infections (STIs). To the best of our knowledge, this is the first systematic review and meta-analysis comparing women’s sexual health outcomes between those who groom and those who don’t.

Methods

We followed the MOOSE guidelines and conducted a computerized-based search using (PubMed, Web of Science, Scopus, and Ovid Medline), till June 20th, 2022, for eligible studies using the relevant keywords; (pubic hair grooming) OR (pubic hair removal OR Genital hairless OR Bikini hair removal OR pubic hair depilation). Cross-sectional studies included which compared grooming practices among women in terms of motivation and health outcomes. Women’s satisfaction and incidence of STIs were pooled as standardized mean difference (SMD) and odds ratio (OR) respectively.

Results

Twenty-Two cross-sectional studies were included in our review with 73,091 participant.The odds of having gram-negative gonorrheal and chlamydial infection in Pubic hair groomers were found to be statistically significant (OR = 1.55, 95% CI [1.31, 1.84], P < 0.001) (OR = 1.56, 95% CI [1.32, 1.85], P < 0.001] respectively. There was no difference between groomer and non-groomer women regarding viral infections such as genital herpes (OR = 1.40, 95% CI [0.56, 3.50], P = 0.47) and Condyloma acuminata (OR = 1.75, 95% CI [0.51, 6.01], P = 0.37). The most common grooming side effect is genital itching (prevalence = 26.9%, P < 0.001). Non-electrical razor (prevalence = 69.3%, P < 0.001) is the most common grooming method. White women (prevalence = 80.2%, P < 0.001) remove pubic hair more frequently compared to black women (prevalence = 12.2%, P < 0.001). Women practice complete grooming (50.3%, P < 0.001) of the pubic hair more frequently than partial grooming (33.1%, P < 0.001). There are no differences in women’s satisfaction between the two groups (SMD = 0.12, 95% CI [-0.16, 0.40], P = 0.39).

Conclusion

This review aligns with previous observational studies regarding sexual health outcomes of pubic hair grooming. There is a need to raise awareness among women regarding the safe practice of pubic hair grooming, emphasizing the clarification of hazards and benefits.
Development and validation of ‘Patient Optimizer’ (POP) algorithms for predicting surgical risk with machine learning
Authors: Kowadlo Gideon , Mittelberg Yoel , Ghomlaghi Milad , Stiglitz Daniel K. , Kishore Kartik , Guha Ranjan , Nazareth Justin , Weinberg Laurence
Published: March 2024

Background

Pre-operative risk assessment can help clinicians prepare patients for surgery, reducing the risk of perioperative complications, length of hospital stay, readmission and mortality. Further, it can facilitate collaborative decision-making and operational planning.

Objective

To develop effective pre-operative risk assessment algorithms (referred to as Patient Optimizer or POP) using Machine Learning (ML) that predict the development of post-operative complications and provide pilot data to inform the design of a larger prospective study.

Methods

After institutional ethics approval, we developed a base model that encapsulates the standard manual approach of combining patient-risk and procedure-risk. In an automated process, additional variables were included and tested with 10-fold cross-validation, and the best performing features were selected. The models were evaluated and confidence intervals calculated using bootstrapping. Clinical expertise was used to restrict the cardinality of categorical variables (e.g. pathology results) by including the most clinically relevant values. The models were created with logistic regression (LR) and extreme gradient-boosted trees using XGBoost (Chen and Guestrin, 2016). We evaluated performance using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Data was obtained from a metropolitan university teaching hospital from January 2015 to July 2020. Data collection was restricted to adult patients undergoing elective surgery.

Results

A total of 11,475 adult admissions were included. The performance of XGBoost and LR was very similar across endpoints and metrics. For predicting the risk of any post-operative complication, kidney failure and length-of-stay (LOS), POP with XGBoost achieved an AUROC (95%CI) of 0.755 (0.744, 0.767), 0.869 (0.846, 0.891) and 0.841 (0.833, 0.847) respectively and AUPRC of 0.651 (0.632, 0.669), 0.336 (0.282, 0.390) and 0.741 (0.729, 0.753) respectively. For 30-day readmission and in-patient mortality, POP with XGBoost achieved an AUROC (95%CI) of 0.610 (0.587, 0.635) and 0.866 (0.777, 0.943) respectively and AUPRC of 0.116 (0.104, 0.132) and 0.031 (0.015, 0.072) respectively.

Conclusion

The POP algorithms effectively predicted any post-operative complication, kidney failure and LOS in the sample population. A larger study is justified to improve the algorithm to better predict complications and length of hospital stay. A larger dataset may also improve the prediction of additional specific complications, readmission and mortality.
Understanding the use of digital technologies to provide disability services remotely during the COVID-19 pandemic; a multiple case study design
Authors: Fortune Jennifer , Manikandan Manjula , Harrington Sarah , Hensey Owen , Kerr Claire , Koppe Sebastian , Kroll Thilo , Lavelle Grace , Long Siobhán , MacLachlan Malcolm , Nolan Denis , Norris Meriel , O’Reilly Jason , Owens Mary , Walsh Aisling , Walsh Michael , Ryan Jennifer M.
Published: March 2024

Background

Using digital technologies to provide services and supports remotely may improve efficiency and accessibility of healthcare, and support people with disabilities to live independently. This study aimed to explore the experience of using digital technologies to access and provide disability services and supports during the Covid-19 pandemic, from the perspective of people with disabilities, families and service providers.

Methods

Using a multiple case study design, we purposively sampled three cases based on service user characteristics and geographical reach of the service. We conducted semi-structured interviews with 40 service users and service providers. Topic guides and analysis were informed by the Consolidated Framework for Implementation Research (CFIR). Analysis followed a largely deductive approach, using the CFIR constructs as a coding framework. A summary memo was developed for each case. Influence and strength of each construct was rated to identify constructs that influenced implementation of digital technologies. Ratings were compared across services to identify facilitators and barriers to implementation.

Results

Service users and providers were positive about using digital technologies to access and provide disability services and supports remotely. Advantages over in-person delivery included reduced travel time, increased opportunity for peer support and peer learning, more choice and opportunity to participate in activities, and an enhanced sense of self while accessing services from the secure environment of their home. The urgency to identify new modes of service delivery to meet the needs of service users during Covid-19 was a strong facilitator but did not necessarily result in successful implementation. Other factors that were strong facilitators were the use of adaptations to enable service users to access the online service, service users’ willingness to try the online service, service users’ persistence when they encountered challenges, and the significant time and effort that service providers made to support service users to participate in the online service. Barriers to implementation included the complexity of accessing online platforms, poor design quality of online platforms, and organisations prioritising in-person delivery over online services.

Conclusions

These findings may allow service providers to leverage facilitators that support implementation of online disability services and supports.
COVID-19-associated costs and mortality in Germany: an incidence-based analysis from a payer’s perspective
Authors: Brandt Florian , Simone Giancarlo , Loth Jörg , Schilling Daniel
Published: March 2024

Background

This study aims to estimate average COVID-19-associated healthcare costs per capita in Germany from a payer perspective. In addition, insights into COVID-19-associated mortality should be gained.

Methods

For this purpose, a retrospective longitudinal analysis using health insurance claims data was performed. Patients affected by COVID-19 in Q1/2021 (investigation group (IG)) were compared to a matched non-COVID-19 control group (CG) (1:1 propensity score matching (PSM)). Mean values of healthcare costs in 2020 and 2021 were computed for both groups and then separated by age and by development of Post-COVID-19 Syndrome (PCS). Group differences were examined using Mann–Whitney U test (α = 0.05). Difference-in-Differences approach (DiD) was used to estimate average cost effects of COVID-19 in 2021. Concerning mortality, the number of deaths in 2021 was compared between IG and CG using χ2 test of independence.

Results

A total of 8,014 insurants were included (n = 4,007 per group; n = 536 per group examining PCS patients only). Total healthcare costs varied a lot in the sample, were comparable between IG and CG in 2020, but were significantly higher in the IG in 2021 (DiD estimate = € 1,063 (in total); € 3,242 (PCS group)). This was more pronounced in the older age groups. High hospital costs of a minority of patients were the most influential driver of COVID-19-associated healthcare costs. Mortality was more than doubled in the IG (tripled in patients aged ≥ 60).

Conclusions

COVID-19 is associated with significantly increased healthcare costs and mortality, especially in older age groups. The additional development of PCS further increases the costs of COVID-19.
CheV enhances the virulence of Salmonella Enteritidis, and the Chev-deleted Salmonella vaccine provides immunity in mice
Authors: Zhang Lu , Wu Tonglei , Wang Fengjie , Liu Wan , Zhao Guixin , Zhang Yanying , Zhang Zhiqiang , Shi Qiumei
Published: March 2024

Background

Salmonella enteritidis (SE) is a major zoonotic pathogen and causes infections in a variety of hosts. The development of novel vaccines for SE is necessary to eradicate this pathogen. Genetically engineered attenuated live vaccines are more immunogenic and safer. Thus, to develop a live attenuated Salmonella vaccine, we constructed a cheV gene deletion strain of SE (named ΔcheV) and investigated the role of cheV in the virulence of SE. First, the ability to resist environmental stress in vitro, biofilm formation capacity, drug resistance and motility of ΔcheV were analyzed. Secondly, the bacterial adhesion, invasion, intracellular survival assays were performed by cell model. Using a mouse infection model, an in vivo virulence assessment was conducted. To further evaluate the mechanisms implicated by the reduced virulence, qPCR analysis was utilized to examine the expression of the strain’s major virulence genes. Finally, the immune protection rate of ΔcheV was evaluated using a mouse model.

Results

Compared to C50336, the ΔcheV had significantly reduced survival ability under acidic, alkaline and thermal stress conditions, but there was no significant difference in survival under oxidative stress conditions. There was also no significant change in biofilm formation ability, drug resistance and motility. It was found that the adhesion ability of ΔcheV to Caco-2 cells remained unchanged, but the invasion ability and survival rate in RAW264.7 cells were significantly reduced. The challenge assay results showed that the LD50 values of C50336 and ΔcheV were 6.3 × 105 CFU and 1.25 × 107 CFU, respectively. After the deletion of the cheV gene, the expression levels of fimD, flgG, csgA, csgD, hflK, lrp, sipA, sipB, pipB, invH, mgtC, sodC, rfbH, xthA and mrr1 genes were significantly reduced. The live attenuated ΔcheV provided 100% protection in mice against SE infection.

Conclusion

All the results confirmed that the deletion of the cheV gene reduces the virulence of SE and provides significant immune protection in mice, indicating that ΔcheV could be potential candidates to be explored as live-attenuated vaccines.
Associations of a plant-centered diet and lung function across early to mid-adulthood: The CARDIA Lung Study
Authors: Wharton Robert C. , Wang Jing Gennie , Choi Yuni , Eisenberg Elliot , Jackson Mariah K. , Hanson Corrine , Liu Bian , Washko George R. , Kalhan Ravi , Jacobs David R. , Bose Sonali
Published: March 2024

Background

Lung function throughout adulthood predicts morbidity and mortality even among adults without chronic respiratory disease. Diet quality may represent a modifiable risk factor for lung function impairment later in life. We investigated associations between nutritionally-rich plant-centered diet and lung function across early and middle adulthood from the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Methods

Diet was assessed at baseline and years 7 and 20 of follow-up using the validated CARDIA diet history questionnaire. Plant-centered diet quality was scored using the validated A Priori Diet Quality Score (APDQS), which weights food groups to measure adherence to a nutritionally-rich plant-centered diet for 20 beneficially rated foods and 13 adversely rated foods. Scores were cumulatively averaged over follow-up and categorized into quintiles. The primary outcome was lung function decline, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), measured at years 0, 2, 5, 10, 20, and 30. We estimated the association of APDQS with annual pulmonary function changes and cross-sectional differences in a repeated measures regression model, adjusting for clinically relevant covariates.

Results

The study included 3,787 Black and White men and women aged 18–30 in 1985–86 and followed for 30 years. In multivariable repeated measures regression models, individuals in the lowest APDQS quintile (poorest diet) had declines in FEV1 that were 1.6 ml/year greater than individuals in the highest quintile (35.0 vs. 33.4 ml/year, ß ± SE per 1 SD change APDQS 0.94 ± 0.36, p = 0.009). Additionally, declines in FVC were 2.4 ml/year greater in the lowest APDQS quintile than those in the highest quintile (37.0 vs 34.6 ml/year, ß ± SE per 1 SD change APDQS 1.71 ± 0.46, p < 0.001). The association was not different between never and ever smokers (pint = 0.07 for FVC and 0.32 for FEV1). In sensitivity analyses where current asthma diagnosis and cardiorespiratory fitness were further adjusted, results remained similar. Cross-sectional analysis at each exam year also showed significant differences in lung function according to diet after covariate adjustment.

Conclusions

In this 30-year longitudinal cohort study, long-term adherence to a nutritionally-rich plant-centered diet was associated with cross-sectional differences in lung function as well as slower decline in lung function, highlighting diet quality as a potential treatable trait supporting long-term lung health.
Quercetin improves epithelial regeneration from airway basal cells of COPD patients
Authors: McCluskey Elizabeth S. , Liu Nathan , Pandey Abhimaneu , Marchetti Nathaniel , Kelsen Steven G. , Sajjan Umadevi S.
Published: March 2024

Background

Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces airway epithelial remodeling and inflammation in COPD models, therefore we examined whether quercetin promotes normal epithelial regeneration from COPD BC by altering gene expression.

Methods

COPD BC treated with DMSO or 1 µM quercetin for three days were cultured at air/liquid interface (ALI) for up to 4 weeks. BC from healthy donors cultured at ALI were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA respectively. Microarray analysis was conducted on DMSO or 1 µM quercetin-treated COPD BC for 3 days to identify differentially regulated genes (DEG). Bronchial brushings obtained from COPD patients with similar age and disease status treated with either placebo (4 subjects) or 2000 mg/day quercetin (7 subjects) for 6 months were used to confirm the effects of quercetin on gene expression.

Results

Compared to placebo-, quercetin-treated COPD BC showed significantly increased transepithelial resistance, more ciliated cells, fewer goblet cells, and lower IL-8. Quercetin upregulated genes associated with tissue and epithelial development and differentiation in COPD BC. COPD patients treated with quercetin, but not placebo showed increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD BC with FDR < 0.001. Active smokers showed increased mRNA expression of TGF-β (0.067) and IL-8 (22.0), which was reduced by 3.6 and 4.14 fold respectively after quercetin treatment.

Conclusions

These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD.

Trial registration

This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.
Cardiopulmonary exercise test to detect cardiac dysfunction from pulmonary vascular disease
Authors: Alotaibi Mona , Yang Jenny Z. , Papamatheakis Demosthenes G. , McGuire W. Cameron , Fernandes Timothy M. , Morris Timothy A.
Published: March 2024

Background

Cardiac dysfunction from pulmonary vascular disease causes characteristic findings on cardiopulmonary exercise testing (CPET). We tested the accuracy of CPET for detecting inadequate stroke volume (SV) augmentation during exercise, a pivotal manifestation of cardiac limitation in patients with pulmonary vascular disease.

Methods

We reviewed patients with suspected pulmonary vascular disease in whom CPET and right heart catheterization (RHC) measurements were taken at rest and at anaerobic threshold (AT). We correlated CPET-determined O2·pulseAT/O2·pulserest with RHC-determined SVAT/SVrest. We evaluated the sensitivity and specificity of O2·pulseAT/O2·pulserest to detect SVAT/SVrest below the lower limit of normal (LLN). For comparison, we performed similar analyses comparing echocardiographically-measured peak tricuspid regurgitant velocity (TRVpeak) with SVAT/SVrest.

Results

From July 2018 through February 2023, 83 simultaneous RHC and CPET were performed. Thirty-six studies measured O2·pulse and SV at rest and at AT. O2·pulseAT/O2·pulserest correlated highly with SVAT/SVrest (r = 0.72, 95% CI 0.52, 0.85; p < 0.0001), whereas TRVpeak did not (r = -0.09, 95% CI -0.47, 0.33; p = 0.69). The AUROC to detect SVAT/SVrest below the LLN was significantly higher for O2·pulseAT/O2·pulserest (0.92, SE 0.04; p = 0.0002) than for TRVpeak (0.69, SE 0.10; p = 0.12). O2·pulseAT/O2·pulserest of less than 2.6 was 92.6% sensitive (95% CI 76.6%, 98.7%) and 66.7% specific (95% CI 35.2%, 87.9%) for deficient SVAT/SVrest.

Conclusions

CPET detected deficient SV augmentation more accurately than echocardiography. CPET-determined O2·pulseAT/O2·pulserest may have a prominent role for noninvasive screening of patients at risk for pulmonary vascular disease, such as patients with persistent dyspnea after pulmonary embolism.
Efficacy and safety of orlistat in male patients with overweight/obesity and hyperuricemia: results of a randomized, double-blind, placebo-controlled trial
Authors: Liu Shuang , Lin Xiaojing , Tao Minghao , Chen Qi , Sun Hang , Han Yali , Yang Shaoling , Gao Yining , Qu Shen , Chen Haibing
Published: March 2024

Background

Obesity is associated with elevated serum uric acid (SUA) levels and frequent gout flares. Losing weight can reduce the SUA level and gout flares. The effect of orlistat on SUA levels and gout flares in patients with overweight/obesity and hyperuricemia (HUA) has not been extensively studied. This study investigated the effects of orlistat on SUA levels and gout flares compared to placebo in overweight and obese patients with HUA.

Methods

A total of 72 Chinese patients with overweight/obesity and HUA were randomly divided into a placebo group (35, 48.6%) and an orlistat group (37, 51.4%); the trial lasted 12 weeks. The primary endpoints were the relative changes in body weight, the SUA level, and gout flares in the per-protocol population.

Results

Orlistat reduced the proportion of patients with gout flares (log-rank P = 0.023, hazard ratio = 0.31, 95% confidence interval 0.11–0.85). There was no significant difference in SUA level between the two groups. The average weight loss of the orlistat group was 2.85 kg, and the average weight loss of the placebo group was 0.76 kg. The weight loss in the orlistat group was significantly greater than that in the control group (P < 0.05).

Conclusions

This study is the first to demonstrate that orlistat has no significant effect on SUA levels in patients with overweight/obesity and HUA. The utility of orlistat as an adjunct therapy to prevent gout flares during weight loss in patients with HUA was emphasized.

Trial registration

Clinicaltrials.gov NCT05496075.
Remnant cholesterol is correlated with retinal vascular morphology and diabetic retinopathy in type 2 diabetes mellitus: a cross-sectional study
Authors: Chen Shuli , Xu Yi , Chen Bo , Lin Senlin , Lu Lina , Cheng Minna , Wang Yuheng , Yang Qinping , Ling Saiguang , Zhou Dengji , Shi Yan , Zou Haidong , Ma Yingyan
Published: March 2024

Background

The association between remnant cholesterol (RC) and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) remains unclear. Morphological changes in retinal vessels have been reported to predict vascular complications of diabetes, including DR.

Methods

This cross-sectional study included 6535 individuals with T2DM. The RC value was calculated using the recognized formula. The retinal vascular parameters were measured using fundus photography. The independent relationship between RC and DR was analyzed using binary logistic regression models. Multiple linear regression and subgroup analyses were employed to investigate the link between RC and vascular parameters, including the retinal arteriolar diameter (CRAE), venular diameter (CRVE), and fractal dimension (Df). Mediation analysis was performed to assess whether the vascular morphology could explain the association between RC and DR.

Results

RC was independently associated with DR in patients with a longer duration of T2DM (> 7 years). Patients with the highest quartile RC levels had larger CRAE (5.559 [4.093, 7.025] μm), CRVE (7.620 [5.298, 9.941] μm) and Df (0.013 [0.009, 0.017]) compared with patients with the lowest quartile RC levels. Results were robust across different subgroups. The association between RC and DR was mediated by CRVE (0.020 ± 0.005; 95% confidence interval: 0.012–0.032).

Conclusions

RC may be a risk factor for DR among those who have had T2DM for a longer period of time. Higher RC levels were correlated with wider retinal arterioles and venules as well as higher Df, and it may contribute to DR through the dilation of retinal venules.
Microneedles loaded with cerium-manganese oxide nanoparticles for targeting macrophages in the treatment of rheumatoid arthritis
Authors: Xia Tian , Zhu Yuting , Li Kaiqiang , Hao Ke , Chai Yingqian , Jiang Hongyi , Lou Chao , Yu Jiachen , Yang Wei , Wang Jilong , Deng Junjie , Wang Zhen
Published: March 2024

Background

Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery.

Result

This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype.

Conclusion

This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming.
The intracellular interplay between galectin-1 and FGF12 in the assembly of ribosome biogenesis complex
Authors: Gędaj Aleksandra , Chorążewska Aleksandra , Ciura Krzysztof , Karelus Radosław , Żukowska Dominika , Biaduń Martyna , Kalka Marta , Zakrzewska Małgorzata , Porębska Natalia , Opaliński Łukasz
Published: March 2024

Galectins constitute a class of lectins that specifically interact with β-galactoside sugars in glycoconjugates and are implicated in diverse cellular processes, including transport, autophagy or signaling. Since most of the activity of galectins depends on their ability to bind sugar chains, galectins exert their functions mainly in the extracellular space or at the cell surface, which are microenvironments highly enriched in glycoconjugates. Galectins are also abundant inside cells, but their specific intracellular functions are largely unknown. Here we report that galectin-1, -3, -7 and -8 directly interact with the proteinaceous core of fibroblast growth factor 12 (FGF12) in the cytosol and in nucleus. We demonstrate that binding of galectin-1 to FGF12 in the cytosol blocks FGF12 secretion. Furthermore, we show that intracellular galectin-1 affects the assembly of FGF12-containing nuclear/nucleolar ribosome biogenesis complexes consisting of NOLC1 and TCOF1. Our data provide a new link between galectins and FGF proteins, revealing an unexpected glycosylation-independent intracellular interplay between these groups of proteins.