bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR-Cas3 and type I restriction-modification team up against blaKPC-IncF plasmid transfer in Klebsiella pneumoniae
Authors: Yang Yang , Zhou Peiyao , Tian Dongxing , Wang Weiwen , Zhou Ying , Jiang Xiaofei
Published: July 2024

Objective

We explored whether the Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification (R-M) systems are compatible and act together to resist plasmid attacks.

Methods

932 global whole-genome sequences from GenBank, and 459 K. pneumoniae isolates from six provinces of China, were collected to investigate the co-distribution of CRISPR-Cas, R-M systems, and blaKPC plasmid. Conjugation and transformation assays were applied to explore the anti-plasmid function of CRISPR and R-M systems.

Results

We found a significant inverse correlation between the presence of CRISPR and R-M systems and blaKPC plasmids in K. pneumoniae, especially when both systems cohabited in one host. The multiple matched recognition sequences of both systems in blaKPC-IncF plasmids (97%) revealed that they were good targets for both systems. Furthermore, the results of conjugation assay demonstrated that CRISPR-Cas and R-M systems in K. pneumoniae could effectively hinder blaKPC plasmid invasion. Notably, CRISPR-Cas and R-M worked together to confer a 4-log reduction in the acquisition of blaKPC plasmid in conjugative events, exhibiting robust synergistic anti-plasmid immunity.

Conclusions

Our results indicate the synergistic role of CRISPR and R-M in regulating horizontal gene transfer in K. pneumoniae and rationalize the development of antimicrobial strategies that capitalize on the immunocompromised status of KPC-KP.
Trunk distortion weakens the tree productivity revealed by half-sib progeny determination of Pinus yunnanensis
Authors: Li Zhongmu , Gao Chengjie , Che Fengxian , Li Jin , Wang Lu , Cui Kai
Published: July 2024

Twisted trunks are not uncommon in trees, but their effects on tree growth are still unclear. Among coniferous tree species, the phenomenon of trunk distortion is more prominent in Pinus yunnanensis. To expand the germplasm of genetic resources, we selected families with excellent phenotypic traits to provide material for advanced generation breeding. The progeny test containing 93 superior families (3240 trees) was used as the research material. Phenotypic measurements and estimated genetic parameters (family heritability, realistic gain and genetic gain) were performed at 9, 15, and 18 years of age, respectively. The genetic evaluation yielded the following results (1) The intra-family variance component of plant height (PH) was greater than that of the inter-family, while the inter-family variance components of other traits (diameter at breast height (DBH), crown diameter (CD), height under branches (HUB), degree of stem-straightness (DS)) were greater than that of the intra-family, indicating that there was abundant variation among families and potential for selection. (2) At half rotation period (18 years old), there was a significant correlation among the traits. The proportion of trees with twisted trunks (level 1–3 straightness) reached 48%. The DS significantly affected growth traits, among which PH and DBH were the most affected. The volume loss rate caused by twisted trunk was 18.06-56.75%, implying that trunk distortion could not be completely eliminated after an artificial selection. (3) The influence of tree shape, crown width, and trunk on volume increased, and the early-late correlation between PH, DBH and volume was extremely significant. The range of phenotypic coefficient of variation, genetic variation coefficient and family heritability of growth traits (PH, DBH, and volume) were 44.29-127.13%, 22.88-60.87%, and 0.79–0.83, respectively. (4) A total of 21 superior families were selected by the method of membership function combined with independent selection. Compared with the mid-term selection (18 years old), the accuracy of early selection (9 years old) reached 77.5%. The selected families’ genetic gain and realistic gain range were 5.79-19.82% and 7.12-24.27%, respectively. This study can provide some useful reference for the breeding of coniferous species.
Severe CSF immune cell alterations in cryptococcal meningitis gradually resolve during antifungal therapy
Authors: Dambietz Christine , Heming Michael , Brix Tobias J. , Schulte-Mecklenbeck Andreas , Tepasse Phil-Robin , Gross Catharina C. , Trebicka Jonel , Wiendl Heinz , Meyer zu Hörste Gerd
Published: July 2024

Cryptococcal meningitis (CM) is a severe fungal disease in immunocompromised patients affecting the central nervous system (CNS). Host response and immunological alterations in the cerebrospinal fluid (CSF) after invasion of Cryptococcus neoformans to the central nervous system have been investigated before but rigorous and comprehensive studies examining cellular changes in the CSF of patients with cryptococccal meningitis are still rare. We retrospectively collected CSF analysis and flow cytometry data of CSF and blood in patients with CM (n = 7) and compared them to HIV positive patients without meningitis (n = 13) and HIV negative healthy controls (n = 7). Within the group of patients with CM we compared those with HIV infection (n = 3) or other immunocompromised conditions (n = 4). Flow cytometry analysis revealed an elevation of natural killer cells and natural killer T cells in the CSF and blood of HIV negative patients with CM, pointing to innate immune activation in early stages after fungal invasion. HIV positive patients with CM exhibited stronger blood-CSF-barrier disruption. Follow-up CSF analysis over up to 150 days showed heterogeneous cellular courses in CM patients with slow normalization of CSF after induction of antifungal therapy.
Growth charts for children aged 6–17 years in Shanxi, China: comparison with other cities of China and WHO
Authors: Hou Guoqiang , Li Kunkun , Cao Wenjun , Tao Mengmeng , Tian Wei , Chang Ruimin
Published: July 2024

Background

Growth charts are an important method for evaluating a child’s health, growth, and nutritional status. It is essential to monitor the growth of children and adolescents using growth charts.

Objectives

To present body mass index (BMI)-for-age references reflecting children’s growth in Shanxi. We also compare our new data with growth references of other cities of China and World Health Organization (WHO) growth standards.

Methods

A stratified cluster random sampling method was used to recruit 5461 children and adolescents aged 6–17 years. Height and weight were measured and BMI was calculated. The LMS method was used to calculate the percentile values of body mass index by sex and age. Smoothed BMI-for-age growth curves were presented for both sexes and compared with reference data from other cities of China and WHO.

Results

BMI centiles increased with age but with different patterns in both boys and girls. The centile curves from the 3rd to the 50th had a slight increase, while a sharp increase was seen from 11 to 17 years in boys and from 6 to 14 years in girls in the higher centiles. In comparison with other cities of China, the values for the 50th percentile are higher than those reported for children from China 2009, Shanghai, Changsha and China 2010 in both sexes. In comparison with WHO growth references, Chinese girls and boys had higher values in all percentiles, whereas curves of girls look roughly the same. The medians for BMI in Shanxi increase linearly from 6 to 17 years in boys.

Conclusions

The BMI percentiles of children aged 6–17 years in Shanxi differed significantly from the growth reference curves of other cities of China and WHO. Recommending the provision of BMI reference curves for local children and adolescents to assess their growth and development and monitor their nutritional status.

Early detection of overweight and obesity in children provides a scientific basis for the prevention and control of overweight and obesity in children.
Experiences from patients in mental healthcare accessing their electronic health records: results from a cross-national survey in Estonia, Finland, Norway, and Sweden
Authors: Fagerlund A.J. , Bärkås Annika , Kharko A. , Blease C.R. , Hagström J. , Huvila I. , Hörhammer I. , Kane B. , Kristiansen E. , Kujala S. , Moll J. , Rexhepi H. , Scandurra I. , Simola S. , Soone H. , Wang B. , Åhlfeldt R.M. , Hägglund M. , Johansen M.A.
Published: July 2024

Background

Patients’ online record access (ORA) enables patients to read and use their health data through online digital solutions. One such solution, patient-accessible electronic health records (PAEHRs) have been implemented in Estonia, Finland, Norway, and Sweden. While accumulated research has pointed to many potential benefits of ORA, its application in mental healthcare (MHC) continues to be contested. The present study aimed to describe MHC users’ overall experiences with national PAEHR services.

Methods

The study analysed the MHC-part of the NORDeHEALTH 2022 Patient Survey, a large-scale multi-country survey. The survey consisted of 45 questions, including demographic variables and questions related to users’ experiences with ORA. We focused on the questions concerning positive experiences (benefits), negative experiences (errors, omissions, offence), and breaches of security and privacy. Participants were included in this analysis if they reported receiving mental healthcare within the past two years. Descriptive statistics were used to summarise data, and percentages were calculated on available data.

Results

6,157 respondents were included. In line with previous research, almost half (45%) reported very positive experiences with ORA. A majority in each country also reported improved trust (at least 69%) and communication (at least 71%) with healthcare providers. One-third (29.5%) reported very negative experiences with ORA. In total, half of the respondents (47.9%) found errors and a third (35.5%) found omissions in their medical documentation. One-third (34.8%) of all respondents also reported being offended by the content. When errors or omissions were identified, about half (46.5%) reported that they took no action. There seems to be differences in how patients experience errors, omissions, and missing information between the countries. A small proportion reported instances where family or others demanded access to their records (3.1%), and about one in ten (10.7%) noted that unauthorised individuals had seen their health information.

Conclusions

Overall, MHC patients reported more positive experiences than negative, but a large portion of respondents reported problems with the content of the PAEHR. Further research on best practice in implementation of ORA in MHC is therefore needed, to ensure that all patients may reap the benefits while limiting potential negative consequences.
Nutritional status and dietary intake among Nigerian adolescent: a systematic review
Authors: Abubakar Hadiza Abdullahi , Shahril Mohd Razif , Mat Sumaiyah
Published: July 2024

Introduction

The prevailing nutritional conditions and the triple challenge of malnutrition faced by adolescents have adverse consequences for both the present and future generations’ health and nutrition. Summarizing the available research on the nutritional status and dietary habits of adolescents in Nigeria is crucial.

Objective

This study aims to systematically evaluate available literature on the nutritional status of adolescent aged 10 to 19years in Nigeria.

Methodology

A systematic search using PRISMA guideline was conducted. Three electronic databases were searched i.e., PubMed, Web of Science and Scopus using specific terms and keywords for online articles published between 2013 and 2023. After applying specified inclusion and exclusion criteria, 51 articles were selected for data extraction, synthesis and quality assessment.

Results

Of the 51 included studies, 78.4% were conducted in the Southern Nigeria, 11.8% in the Northern Nigeria and 9.8% included both regions. The prevalence of overweight ranged between 0.8 and 31% and obesity ranged between 0.1 and 14%. The prevalence of thinness, stunting and underweight ranged between 3 and 31%, 0.4 to 41.6%, 0.3 to 73.3% respectively. The review also identified an inadequate intake of essential nutrients including iron, zinc, calcium, vitamin A, C, D, niacin, thiamin, riboflavin, cobalamin, and folate, with vitamin A deficiency prevalence ranges from 44 to 96%. The dietary patterns were characterized by a high consumption of cereals grains and starchy foods, low animal proteins, fast-food with soft drinks, and limited consumption of fruits and vegetables along with meal skipping.

Conclusion

These findings portray a complex picture of the nutritional challenges faced by this demographic group, highlighting both undernutrition and overnutrition, poor eating behaviour and micronutrient deficiency as significant concerns. The review revealed regional disparities in research representation, with a concentration of studies in Southern Nigeria. This highlights the importance of directing research efforts toward the northern regions, where the prevalence of nutritional issues is equally severe, but less studied.

Systematic review registration number

PROSPERO CRD42023481095.
Period poverty, reuse needs, and depressive symptoms among refugee menstruators in Jordan’s camps: a cross-sectional study
Authors: Muhaidat Nadia , Karmi Joud Al , Karam Abdulrahman M. , Abushaikha Farah , Alshrouf Mohammad Ali
Published: July 2024

Background

Period poverty is a significant issue that impacts the physical and psychological well-being of menstruators worldwide which can further contribute to poor mental health outcomes. For menstruators living in refugee camps, access to menstrual hygiene products is often limited or non-existent, leading to increased anxiety, shame, and embarrassment. Therefore, this study aimed to assess the prevalence of the period poverty and to comprehensively analyze the association between period poverty, reusing menstrual products, and depressive symptoms among menstruators living in refugee camps in Jordan.

Methods

A cross-sectional study surveyed refugee menstruators living in camps in Jordan, aged post-menarche to pre-menopause. Data collection included socio-demographics, menstrual practices, and depressive symptoms using the Patient Health Questionnaire (PHQ-9). Period poverty was assessed through affordability and frequency of struggles with menstrual products. Chi-squared test, independent sample t-test, One Way Analysis of variance (ANOVA) followed by Post hoc, and logistic regression models were used in the analysis.

Results

The study included a diverse sample of 386 refugee menstruators living in camps in Jordan (mean age 32.43 ± 9.95, age range 13–55). Period poverty was highly prevalent, with 42.0% reporting monthly struggles to afford menstrual products, and 71.5% reusing menstrual products. Univariate analysis revealed that experiencing period poverty was significantly associated with a younger age of marriage, increased number of children, lower education level, lower mother and father education levels, unemployment, decreased monthly income, absence of health insurance, lower reuse need score, and increased PHQ-9 score (p < 0.05). Menstruators experiencing monthly period poverty were 2.224 times more likely to report moderate to severe depression compared to those without period poverty (95% CI 1.069–4.631, P = 0.033).

Conclusion

This study highlights a significant association between period poverty and depressive symptoms among refugee menstruators in living in camps in Jordan, as high rates of period poverty were associated with a 2.2-fold increased likelihood of reporting moderate to severe depression. Addressing period poverty in refugee settings is crucial for mitigating depression risks and enhancing overall well-being.
Optimization of the extraction process for Shenshou Taiyi powder based on Box-Behnken experimental design, standard relation, and FAHP-CRITIC methods
Authors: Jiang Mengcheng , Qiu Zhidong , Diao Yuanyuan , Shi Yuwen , Liu Weipeng , Li Na , Jia Ailing
Published: July 2024

Background

Ancient classic prescription play a crucial role in the preservation and advancement of traditional Chinese medicine (TCM) theories. They represent a significant milestone in the ongoing development and transmission of TCM knowledge and practices and are considered one of the breakthroughs in the development of TCM inheritance. In the process of developing ancient classic prescriptions, many problems may still arise in ensuring quality consistency between traditional methods and modern production processes, among which the extraction process poses major challenges. This paper introduces a practical approach extracting an ancient classic prescription using a modern extraction process. The technique is demonstrated through the study of the extraction process of Shenshou Taiyi powder (STP).

Methods

This study focuses on optimising the STP extraction process to ensure consistency in the quality of the product obtained through ancient and modern processes using the standard relation and fuzzy analytic hierarchical process (FAHP) and criteria importance through intercriteria correlation (CRITIC) method integrated weights combined with the Box-Behnken response surface test. Using the contents of rosmarinic acid, isoimperatorin, puerarin, as well as the extract yield and fingerprint similarity as evaluation indexes of STP, the Box-Behnken response surface method was employed to examine the varying extraction parameters, including water addition ratio, extraction duration, and number of extractions. The weighted coefficients for each parameter were calculated by combining the benchmark correlation and FAHP-CRITIC method, deriving a comprehensive score.

Results

The optimal extraction process for STP consisted of a two extractions, each using at a tenfold quantity of water, performed for one hour. Process verification across three separate batches yielded a comprehensive score of 94.7, with a relative standard deviation of 0.76%.

Conclusions

The application of the Box-Behnken response surface method combined with standard relation and FAHP-CRITIC approach proved to be stable and feasible for optimising the extraction process of STP.
Factors leading to excessive fatigue in nurses – a three-year follow-up study
Authors: Hiestand Stand , Waage Siri , Forthun Ingeborg , Pallesen Ståle , Bjorvatn Bjørn
Published: July 2024

Background

Global nursing shortages necessitate the identification of mitigatable factors that may reduce nursing absence and turnover. Fatigue has been shown to be associated with these issues. This study aimed to identify factors leading to development of or recovery from excessive fatigue in nurses as these can offer actionable avenues for protecting nurses against fatigue or supporting fatigue recovery.

Methods

A longitudinal study among nurses randomly sampled from the Norwegian Nurse’s Organization. The Chalder Fatigue Questionnaire measured fatigue. Dichotomized scoring was used, with scores ≥ 4 considered excessive fatigue. The study included questions on shift work schedules, psychosocial work characteristics, sleep, body mass index, physical activity, caffeine, alcohol, mental health, etc. Two sets of logistic regression analysis were conducted (one for development of and one for recovery from excessive fatigue), evaluating how changes in work, lifestyle and health between baseline (2015) and follow-up (2018) affected first, odds of development of excessive fatigue and second, odds of recovery from excessive fatigue.

Results

Among 1,311 included nurses, 21.6% maintained, 13.3% developed, and 18.0% recovered from excessive fatigue (2015–2018). Within work characteristics, increased psychological work demands were associated with development of excessive fatigue OR = 1.77 (CI = 1.11–2.82). Several work characteristics were associated with recovery from excessive fatigue, including decreased decision latitude (OR = 0.39; CI = 0.19–0.82) and increased coworker support (OR = 1.90; CI = 1.11–3.24). Shift work variables were not associated with fatigue outcomes. Amongst lifestyle factors, changes in sleep duration, obesity, and exercise were significant. Notably, developing inappropriate sleep duration (OR = 2.84; CI = 1.47–5.48) increased odds of developing excessive fatigue, while maintaining inappropriate sleep duration (< 6 h or > 8 h) (OR = 0.19; CI = 0.54–0.65) decreased odds of recovering. All assessed health conditions (depression, anxiety, insomnia, and shift work disorder) were related to development of (ORs 2.10–8.07) or recovery from (ORs 0.10–0.50) excessive fatigue. Depression, for example, increased odds of development of (OR = 8.07; CI = 2.35–27.66) and decreased odds of recovery (OR = 0.10; CI = 0.04–0.26) from excessive fatigue.

Conclusions

Changes in lifestyle factors, health conditions, and psychosocial work factors were associated with development of and recovery from excessive fatigue. Sleep and psychosocial work factors played important roles. We found no relationship with shift work schedules.
The association between primary care appointment lengths and opioid prescribing for common pain conditions
Authors: Matulis John C. , Swanson Kristi , McCoy Rozalina
Published: July 2024

Background

While brief duration primary care appointments may improve access, they also limit the time clinicians spend evaluating painful conditions. This study aimed to evaluate whether 15-minute primary care appointments resulted in higher rates of opioid prescribing when compared to ≥ 30-minute appointments.

Methods

We performed a retrospective cohort study using electronic health record (EHR), pharmacy, and administrative scheduling data from five primary care practices in Minnesota. Adult patients seen for acute Evaluation & Management visits between 10/1/2015 and 9/30/2017 scheduled for 15-minute appointments were propensity score matched to those scheduled for ≥ 30-minutes. Sub-groups were analyzed to include patients with acute and chronic pain conditions and prior opioid exposure. Multivariate logistic regression was performed to examine the effects of appointment length on the likelihood of an opioid being prescribed, adjusting for covariates including ethnicity, race, sex, marital status, and prior ED visits and hospitalizations for all conditions.

Results

We identified 45,471 eligible acute primary care visits during the study period with 2.7% (N = 1233) of the visits scheduled for 15 min and 98.2% (N = 44,238) scheduled for 30 min or longer. Rates of opioid prescribing were significantly lower for opioid naive patients with acute pain scheduled in 15-minute appointments when compared to appointments of 30 min of longer (OR 0.55, 95% CI 0.35–0.84). There were no significant differences in opioid prescribing among other sub-groups.

Conclusions

For selected indications and for selected patients, shorter duration appointments may not result in greater rates of opioid prescribing for common painful conditions.
Efficiency evaluation and promoter identification of primary health care system in China: an enhanced DEA-Tobit approach
Authors: Zeng Zhi , Yu Xiru , Tao Wenjuan , Feng Wei , Zhang Wei
Published: July 2024

Background

With Primary Health Care (PHC) being a cornerstone of accessible, affordable, and effective healthcare worldwide, its efficiency, especially in developing countries like China, is crucial for achieving Universal Health Coverage (UHC). This study evaluates the efficiency of PHC systems in a southwest China municipality post-healthcare reform, identifying factors influencing efficiency and proposing strategies for improvement.

Methods

Utilising a 10-year provincial panel dataset, this study employs an enhanced Data Envelopment Analysis (DEA) model integrating Slack-Based Measure (SBM) and Directional Distance Function (DDF) with the Global Malmquist-Luenberger (GML) index for efficiency evaluation. Tobit regression analysis identifies efficiency determinants within the context of China’s healthcare reforms, focusing on horizontal integration, fiscal spending, urbanisation rates, and workforce optimisation.

Results

The study reveals a slight decline in PHC system efficiency across the municipality from 2009 to 2018. However, the highest-performing county achieved a 2.36% increase in Total Factor Productivity (TFP), demonstrating the potential of horizontal integration reforms and strategic fiscal investments in enhancing PHC efficiency. However, an increase in nurse density per 1,000 population negatively correlated with efficiency, indicating the need for a balanced approach to workforce expansion.

Conclusions

Horizontal integration reforms, along with targeted fiscal inputs and urbanisation, are key to improving PHC efficiency in underdeveloped regions. The study underscores the importance of optimising workforce allocation and skillsets over mere expansion, providing valuable insights for policymakers aiming to strengthen PHC systems toward achieving UHC in China and similar contexts.
Risk of emergency hospital admission related to adverse events after antibiotic treatment in adults with a common infection: impact of COVID-19 and derivation and validation of risk prediction models
Authors: Zhong Xiaomin , Palin Victoria , Ashcroft Darren M. , Goldacre Ben , MacKenna Brian , Mehrkar Amir , Bacon Sebastian C. J. , Massey Jon , Inglesby Peter ,   the OpenSAFELY collaborative, Hand Kieran , Pate Alexander , van Staa Tjeerd Pieter
Published: July 2024

Background

With the global challenge of antimicrobial resistance intensified during the COVID-19 pandemic, evaluating adverse events (AEs) post-antibiotic treatment for common infections is crucial. This study aims to examines the changes in incidence rates of AEs during the COVID-19 pandemic and predict AE risk following antibiotic prescriptions for common infections, considering their previous antibiotic exposure and other long-term clinical conditions.

Methods

With the approval of NHS England, we used OpenSAFELY platform and analysed electronic health records from patients aged 18–110, prescribed antibiotics for urinary tract infection (UTI), lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), sinusitis, otitis externa, and otitis media between January 2019 and June 2023. We evaluated the temporal trends in the incidence rate of AEs for each infection, analysing monthly changes over time. The survival probability of emergency AE hospitalisation was estimated in each COVID-19 period (period 1: 1 January 2019 to 25 March 2020, period 2: 26 March 2020 to 8 March 2021, period 3: 9 March 2021 to 30 June 2023) using the Kaplan–Meier approach. Prognostic models, using Cox proportional hazards regression, were developed and validated to predict AE risk within 30 days post-prescription using the records in Period 1.

Results

Out of 9.4 million patients who received antibiotics, 0.6% of UTI, 0.3% of URTI, and 0.5% of LRTI patients experienced AEs. UTI and LRTI patients demonstrated a higher risk of AEs, with a noted increase in AE incidence during the COVID-19 pandemic. Higher comorbidity and recent antibiotic use emerged as significant AE predictors. The developed models exhibited good calibration and discrimination, especially for UTIs and LRTIs, with a C-statistic above 0.70.

Conclusions

The study reveals a variable incidence of AEs post-antibiotic treatment for common infections, with UTI and LRTI patients facing higher risks. AE risks varied between infections and COVID-19 periods. These findings underscore the necessity for cautious antibiotic prescribing and call for further exploration into the intricate dynamics between antibiotic use, AEs, and the pandemic.
Long-term comparison of renal and metabolic outcomes after sodium–glucose co-transporter 2 inhibitor or glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes
Authors: Sohn Minji , Nam Seoungyeon , Nauck Michael A. , Lim Soo
Published: July 2024

Background

Renal outcomes in patients with type 2 diabetes following treatment with sodium–glucose co-transporter-2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP1RAs) have not been directly compared. This study compared the impact of SGLT2i and GLP1RA therapy on renal function and metabolic parameters.

Methods

Patients with type 2 diabetes who initiated SGLT2i or GLP1RA therapy in a tertiary hospital between January 2009 and August 2023 were included to assess composite renal outcomes, such as a 40% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease, renal death, or new-onset macroalbuminuria. Alterations in blood pressure, glucose regulation parameters, lipid profile, and anthropometric parameters, including body fat and muscle masses, were examined over 4-years.

Results

A total of 2,112 patients were enrolled using a one-to-three propensity-score matching approach (528 patients for GLP1RAs, 1,584 patients for SGLT2i). SGLT2i treatment was favoured over GLP1RA treatment, though not significantly, for composite renal outcomes (hazard ratio [HR], 0.63; p = 0.097). SGLT2i therapy preserved renal function effectively than GLP1RAs (decrease in eGFR, ≥ 40%; HR, 0.46; p = 0.023), with improving albuminuria regression (HR, 1.72; p = 0.036). SGLT2i therapy decreased blood pressure and body weight to a greater extent. However, more patients attained HbA1c levels < 7.0% with GLP1RAs than with SGLT2is (40.6% vs 31.4%; p < 0.001). GLP1RA therapy enhanced β-cell function and decreased LDL-cholesterol levels below baseline values.

Conclusions

SGLT2is were superior for preserving renal function and reducing body weight, whereas GLP1RAs were better for managing glucose dysregulation and dyslipidaemia.
Prolonged increase in psychotropic drug use among young women following the COVID-19 pandemic: a French nationwide retrospective study
Authors: Lamer Antoine , Saint-Dizier Chloé , Levaillant Mathieu , Hamel-Broza Jean-François , Ayed Eiya , Chazard Emmanuel , Bubrovszky Maxime , D’Hondt Fabien , Génin Michael , Horn Mathilde
Published: July 2024

Background

The COVID-19 pandemic has had a significant impact on mental health, with evidence suggesting an enduring mental health crisis. Studies worldwide observed increased usage of antidepressants, anxiolytics, and hypnotics during the pandemic, notably among young people and women. However, few studies tracked consumption post-2021. Our study aimed to fill this gap by investigating whether the surge in the number psychotropic drug consumers in France persisted 2 years after the first lockdown, particularly focusing on age and gender differences.

Methods

We conducted a national retrospective observational study based on the French national insurance database. We retrieved all prescriptions of anxiolytics, hypnotics, and antidepressants dispensed in pharmacies in France for the period 2015–2022. We performed interrupted time series analyses based on Poisson models for five age classes (12–18; 19–25; 26–50; 51–75; 76 and more) to assess the trend before lockdown, the gap induced and the change in trend after.

Results

In the overall population, the number of consumers remained constant for antidepressants while it decreased for anxiolytics and hypnotics. Despite this global trend, a long-term increase was observed in the 12–18 and 19–25 groups for the three drug classes. Moreover, for these age classes, the increases were more pronounced for women than men, except for hypnotics where the trends were similar.

Conclusions

The number of people using antidepressants continues to increase more than 2 years after the first lockdown, showing a prolonged effect on mental health. This effect is particularly striking among adolescents and young adults confirming the devastating long-term impact of the pandemic on their mental health.
Antiviral activity of luteolin against porcine epidemic diarrhea virus in silico and in vitro
Authors: Wang Jieru , Zeng Xiaoyu , Gou Jiaojiao , Zhu Xiaojie , Yin Dongdong , Yin Lei , Shen Xuehuai , Dai Yin , Pan Xiaocheng
Published: July 2024

Background

Porcine epidemic diarrhea virus (PEDV) mainly causes acute and severe porcine epidemic diarrhea (PED), and is highly fatal in neonatal piglets. No reliable therapeutics against the infection exist, which poses a major global health issue for piglets. Luteolin is a flavonoid with anti-viral activity toward several viruses.

Results

We evaluated anti-viral effects of luteolin in PEDV-infected Vero and IPEC-J2 cells, and identified IC50 values of 23.87 µM and 68.5 µM, respectively. And found PEDV internalization, replication and release were significantly reduced upon luteolin treatment. As luteolin could bind to human ACE2 and SARS-CoV-2 main protease (Mpro) to contribute viral entry, we first identified that luteolin shares the same core binding site on pACE2 with PEDV-S by molecular docking and exhibited positive pACE2 binding with an affinity constant of 71.6 µM at dose-dependent increases by surface plasmon resonance (SPR) assay. However, pACE2 was incapable of binding to PEDV-S1. Therefore, luteolin inhibited PEDV internalization independent of PEDV-S binding to pACE2. Moreover, luteolin was firmly embedded in the groove of active pocket of Mpro in a three-dimensional docking model, and fluorescence resonance energy transfer (FRET) assays confirmed that luteolin inhibited PEDV Mpro activity. In addition, we also observed PEDV-induced pro-inflammatory cytokine inhibition and Nrf2-induced HO-1 expression. Finally, a drug resistant mutant was isolated after 10 cell culture passages concomitant with increasing luteolin concentrations, with reduced PEDV susceptibility to luteolin identified at passage 10.

Conclusions

Our results push forward that anti-PEDV mechanisms and resistant-PEDV properties for luteolin, which may be used to combat PED.
Comparing national device-based physical activity surveillance systems: a systematic review
Authors: de Wolf Inge , Elevelt Anne , van Nassau Femke , Toepoel Vera , de Hollander Ellen , Kompier Maaike E. , Luiten Annemieke , Schouten Barry , Wendel-Vos G. C. Wanda , van der Ploeg Hidde P.
Published: July 2024

Background

Physical activity surveillance systems are important for public health monitoring but rely mostly on self-report measurement of physical activity. Integration of device-based measurements in such systems can improve population estimates, however this is still relatively uncommon in existing surveillance systems. This systematic review aims to create an overview of the methodology used in existing device-based national PA surveillance systems.

Methods

Four literature databases (PubMed, Embase.com, SPORTDiscus and Web of Science) were searched, supplemented with backward tracking. Articles were included if they reported on population-based (inter)national surveillance systems measuring PA, sedentary time and/or adherence to PA guidelines. When available and in English, the methodological reports of the identified surveillance studies were also included for data extraction.

Results

This systematic literature search followed the PRISMA guidelines and yielded 34 articles and an additional 18 methodological reports, reporting on 28 studies, which in turn reported on one or multiple waves of 15 different national and 1 international surveillance system. The included studies showed substantial variation between (waves of) systems in number of participants, response rates, population representativeness and recruitment. In contrast, the methods were similar on data reduction definitions (e.g. minimal number of valid days, non-wear time and necessary wear time for a valid day).

Conclusions

The results of this review indicate that few countries use device-based PA measurement in their surveillance system. The employed methodology is diverse, which hampers comparability between countries and calls for more standardized methods as well as standardized reporting on these methods. The results from this review can help inform the integration of device-based PA measurement in (inter)national surveillance systems.
Device-measured sedentary time and intensity-specific physical activity in relation to all-cause and cardiovascular disease mortality: the UK Biobank cohort study
Authors: Rezende Leandro F. M. , Ahmadi Matthew , Ferrari Gerson , del Pozo Cruz Borja , Lee I-Min , Ekelund Ulf , Stamatakis Emmanuel
Published: July 2024

Background and aims

Understanding the amounts of intensity-specific movement needed to attenuate the association between sedentary time and mortality may help to inform personalized prescription and behavioral counselling. Herein, we examined the joint associations of sedentary time and intensity-specific physical activity with all-cause and cardiovascular disease (CVD) mortality.

Methods

Prospective cohort study including 73,729 adults from the UK Biobank who wore an Axivity AX3 accelerometer on their dominant wrist for at least 3 days, being one a weekend day, between June 2013 and December 2015. We considered the median tertile values of sedentary time and physical activity in each intensity band to determine the amount of physical activity needed to attenuate the association between sedentary time and mortality.

Results

During a median of 6.9 years of follow-up (628,807 person-years), we documented 1521 deaths, including 388 from CVD. Physical activity of any intensity attenuated the detrimental association of sedentary time with mortality. Overall, at least a median of 6 min/day of vigorous physical activity, 30 min/day of MVPA, 64 min/day of moderate physical activity, or 163 min/day of light physical activity (mutually-adjusted for other intensities) attenuated the association between sedentary time and mortality. High sedentary time was associated with higher risk of CVD mortality only among participants with low MVPA (HR 1.96; 95% CI 1.23 to 3.14).

Conclusions

Different amounts of each physical activity intensity may attenuate the association between high sedentary time and mortality.
Life’s essential 8, genetic susceptibility, and risk of inflammatory bowel diseases: a population-based cohort study
Authors: Yang Honghao , Chang Qing , Ji Chao , Zheng Gang , Ma Zheng , Chen Liangkai , Xia Yang , Zhao Yuhong
Published: July 2024

Background

Evidence has shown that the individual metrics in Life’s Essential 8 (LE8), an updated cardiovascular health (CVH) concept proposed by the American Heart Association, play a role in the development of inflammatory bowel disease (IBD). However, epidemiological evidence on the overall LE8 on IBD risk remains limited. We aimed to assess the longitudinal associations of LE8-defined CVH and the risks of IBD and its subtypes, ulcerative colitis (UC) and Crohn’s disease (CD). We also tested whether genetic susceptibility could modify these associations.

Methods

A total of 260,836 participants from the UK Biobank were included. LE8 scores were determined by 8 metrics (physical activity, diet, nicotine exposure, sleep, body mass index, blood pressure, blood glucose, and blood lipids), and were divided into three levels: low CVH (0–49), moderate CVH (50–79), and high CVH (80–100). Cox proportional hazards models were used to calculate the hazard ratios (HRs) and confidence intervals (CIs) of the risk of IBD in relation to CVH status.

Results

Over a median follow-up 12.3 years, we documented 1,500 IBD cases (including 1,070 UC and 502 CD). Compared to participants with low CVH, the HRs (95% CIs) of those with high CVH for IBD, UC, and CD were 0.67 (0.52, 0.83), 0.70 (0.52, 0.93), and 0.55 (0.38, 0.80), respectively. These associations were not modified by genetic susceptibility (all P for interactions > 0.05). The lowest HR (UC: 0.30, 95% CI: 0.20–0.45; CD: 0.33, 95% CI: 0.20–0.57) was observed in participants with both high CVH and low genetic risk.

Conclusions

Better CVH, defined by LE8, was associated with significantly lower risks of IBD, UC, and CD, irrespective of genetic predisposition. Our results underscore the importance of adherence to LE8 guidelines for maintaining CVH as a potential strategy in the prevention of IBD.
Radiology of fibrosis. Part I: Thoracic organs
Authors: Tarchi Sofia Maria , Salvatore Mary , Lichtenstein Philip , Sekar Thillai , Capaccione Kathleen , Luk Lyndon , Shaish Hiram , Makkar Jasnit , Desperito Elise , Leb Jay , Navot Benjamin , Goldstein Jonathan , Laifer Sherelle , Beylergil Volkan , Ma Hong , Jambawalikar Sachin , Aberle Dwight , D’Souza Belinda , Bentley-Hibbert Stuart , Marin Monica Pernia
Published: July 2024

Sustained injury from factors such as hypoxia, infection, or physical damage may provoke improper tissue repair and the anomalous deposition of connective tissue that causes fibrosis. This phenomenon may take place in any organ, ultimately leading to their dysfunction and eventual failure. Tissue fibrosis has also been found to be central in both the process of carcinogenesis and cancer progression. Thus, its prompt diagnosis and regular monitoring is necessary for implementing effective disease-modifying interventions aiming to reduce mortality and improve overall quality of life. While significant research has been conducted on these subjects, a comprehensive understanding of how their relationship manifests through modern imaging techniques remains to be established. This work intends to provide a comprehensive overview of imaging technologies relevant to the detection of fibrosis affecting thoracic organs as well as to explore potential future advancements in this field.
Radiology of fibrosis part II: abdominal organs
Authors: Tarchi Sofia Maria , Salvatore Mary , Lichtenstein Philip , Sekar Thillai , Capaccione Kathleen , Luk Lyndon , Shaish Hiram , Makkar Jasnit , Desperito Elise , Leb Jay , Navot Benjamin , Goldstein Jonathan , Laifer Sherelle , Beylergil Volkan , Ma Hong , Jambawalikar Sachin , Aberle Dwight , D’Souza Belinda , Bentley-Hibbert Stuart , Marin Monica Pernia
Published: July 2024

Fibrosis is the aberrant process of connective tissue deposition from abnormal tissue repair in response to sustained tissue injury caused by hypoxia, infection, or physical damage. It can affect almost all organs in the body causing dysfunction and ultimate organ failure. Tissue fibrosis also plays a vital role in carcinogenesis and cancer progression. The early and accurate diagnosis of organ fibrosis along with adequate surveillance are helpful to implement early disease-modifying interventions, important to reduce mortality and improve quality of life. While extensive research has already been carried out on the topic, a thorough understanding of how this relationship reveals itself using modern imaging techniques has yet to be established. This work outlines the ways in which fibrosis shows up in abdominal organs and has listed the most relevant imaging technologies employed for its detection. New imaging technologies and developments are discussed along with their promising applications in the early detection of organ fibrosis.
Tissue of origin detection for cancer tumor using low-depth cfDNA samples through combination of tumor-specific methylation atlas and genome-wide methylation density in graph convolutional neural networks
Authors: Nguyen Trong Hieu , Doan Nhu Nhat Tan , Tran Trung Hieu , Huynh Le Anh Khoa , Doan Phuoc Loc , Nguyen Thi Hue Hanh , Nguyen Van Thien Chi , Nguyen Giang Thi Huong , Nguyen Hoai-Nghia , Giang Hoa , Tran Le Son , Phan Minh Duy
Published: July 2024

Background

Cell free DNA (cfDNA)-based assays hold great potential in detecting early cancer signals yet determining the tissue-of-origin (TOO) for cancer signals remains a challenging task. Here, we investigated the contribution of a methylation atlas to TOO detection in low depth cfDNA samples.

Methods

We constructed a tumor-specific methylation atlas (TSMA) using whole-genome bisulfite sequencing (WGBS) data from five types of tumor tissues (breast, colorectal, gastric, liver and lung cancer) and paired white blood cells (WBC). TSMA was used with a non-negative least square matrix factorization (NNLS) deconvolution algorithm to identify the abundance of tumor tissue types in a WGBS sample. We showed that TSMA worked well with tumor tissue but struggled with cfDNA samples due to the overwhelming amount of WBC-derived DNA. To construct a model for TOO, we adopted the multi-modal strategy and used as inputs the combination of deconvolution scores from TSMA with other features of cfDNA.

Results

Our final model comprised of a graph convolutional neural network using deconvolution scores and genome-wide methylation density features, which achieved an accuracy of 69% in a held-out validation dataset of 239 low-depth cfDNA samples.

Conclusions

In conclusion, we have demonstrated that our TSMA in combination with other cfDNA features can improve TOO detection in low-depth cfDNA samples.
Targeted metabolomics identifies accurate CSF metabolite biomarkers for the differentiation between COVID-19 with neurological involvement and CNS infections with neurotropic viral pathogens
Authors: Neu Frieder , Nay Sandra , Schuchardt Sven , Klawonn Frank , Skripuletz Thomas , Suehs Kurt-Wolfram , Pessler Frank
Published: July 2024

Background

COVID-19 is primarily considered a respiratory tract infection, but it can also affect the central nervous system (CNS), which can result in long-term sequelae. In contrast to CNS infections by classic neurotropic viruses, SARS-CoV-2 is usually not detected in cerebrospinal fluid (CSF) from patients with COVID-19 with neurological involvement (neuro-COVID), suggesting fundamental differences in pathogenesis.

Methods

To assess differences in CNS metabolism in neuro-COVID compared to CNS infections with classic neurotropic viruses, we applied a targeted metabolomic analysis of 630 metabolites to CSF from patients with (i) COVID-19 with neurological involvement [n = 16, comprising acute (n = 13) and post-COVID-19 (n = 3)], (ii) viral meningitis, encephalitis, or myelitis (n = 10) due to herpes simplex virus (n = 2), varicella zoster virus (n = 6), enterovirus (n = 1) and tick-borne encephalitis virus (n = 1), and (iii) aseptic neuroinflammation (meningitis, encephalitis, or myelitis) of unknown etiology (n = 21) as additional disease controls.

Results

Standard CSF parameters indicated absent or low neuroinflammation in neuro-COVID. Indeed, CSF cell count was low in neuro-COVID (median 1 cell/µL, range 0–12) and discriminated it accurately from viral CNS infections (AUC = 0.99) and aseptic neuroinflammation (AUC = 0.98). 32 CSF metabolites passed quality assessment and were included in the analysis. Concentrations of differentially abundant (fold change ≥|1.5|, FDR ≤ 0.05) metabolites were both higher (9 and 5 metabolites) and lower (2 metabolites) in neuro-COVID than in the other two groups. Concentrations of citrulline, ceramide (d18:1/18:0), and methionine were most significantly elevated in neuro-COVID. Remarkably, triglyceride TG(20:1_32:3) was much lower (mean fold change = 0.09 and 0.11) in neuro-COVID than in all viral CNS infections and most aseptic neuroinflammation samples, identifying it as highly accurate biomarker with AUC = 1 and 0.93, respectively. Across all samples, TG(20:1_32:3) concentration correlated only moderately with CSF cell count (ρ = 0.65), protein concentration (ρ = 0.64), and Q-albumin (ρ = 0.48), suggesting that its low levels in neuro-COVID CSF are only partially explained by less pronounced neuroinflammation.

Conclusions

The results suggest that CNS metabolite responses in neuro-COVID differ fundamentally from viral CNS infections and aseptic neuroinflammation and may be used to discover accurate diagnostic biomarkers in CSF and to gain insights into differences in pathophysiology between neuro-COVID, viral CNS infections and aseptic neuroinflammation.