bluuebunny/crossref_metadata_2025 huggingface dataset:
ADHD prescription patterns and medication adherence in children and adolescents during the COVID-19 pandemic in an urban academic setting
Authors: Cunniff Peter J. , Ahsan Amil , McCrary Catherine , Dien Tracy , Kuhn Tristan H. , Vazifedan Turaj , Harrington John W.
Published: March 2024

Background

COVID-19 impacted all students, especially those with attention deficit hyperactivity disorder (ADHD), putting them at risk for disruption to their medication regimen and school performance. Our study aimed to identify if ADHD medication regimens were disrupted through analyzing prescription refills and if telehealth management demonstrated a higher rate of adherence.

Methods

A total of 396 patients from the General Academic Pediatrics (GAP) clinic at Children’s Hospital of The King’s Daughters (CHKD) were included in the study. Patients were between the ages of 8–18 with a history of ADHD for three or more years that was medically managed with four or more prescription refills between January 2019 and May 2022. A retrospective chart review collected age, sex, race, refill schedule, appointment schedule, and number of telehealth appointments. Data analysis compared the variables and defined “pre-pandemic months” as January 2019 through March 2020 and “pandemic months” as April 2020 through June 2022.

Results

The total percentage of patients who had their ADHD medications during pre-pandemic months ranged from 40 to 66% versus 31–44% during pandemic months. Additionally, the total percentage of patients who had quarterly ADHD management appointments during pre-pandemic months ranged between 59 and 70% versus 33–50% during pandemic months. The number of months with ADHD prescription refills over the last three years was significantly higher among those who had both virtual and in-person visits than those who had just in-person visits, p < 0.001. Regarding race, Black patients had a lower number of medication refills compared to White patients when controlled for appointment type. They also had a lower number of total appointments, but there was not a significant difference in the number of virtual appointments.

Conclusions

Since the start of the pandemic, ADHD patients have both refilled their prescriptions and returned to clinic less frequently. This data suggests a need to re-evaluate the ADHD symptoms of GAP patients periodically and return them to a more consistent medication regimen. Telehealth appointments are a potential solution to increase adherence. However, racial inequities found in this study need to be addressed.
Differences in children’s exposure to television advertising of unhealthy foods and beverages in Spain by socio-economic level
Authors: Royo-Bordonada Miguel Ángel , Cavero-Esponera Cristina , Romero-Fernández María Mar , González-Díaz Cristina , Ordaz Castillo Elena
Published: March 2024

Background

The influence of food advertising on food preferences and consumption could also contribute to the socio-economic inequalities among Spanish children in terms of eating habits and childhood obesity. Although the main food advertising channel targeted at children in Spain is television, available studies estimate exposure indirectly by combining content data with audience data. The aim of this study was therefore to describe the frequency of exposure to television advertising of unhealthy foods and drinks, measured directly, among Spanish children and adolescents, and analyse its socio-economic inequalities.

Methods

Observational study of television advertising impacts in a sample of 1590 children aged 4 to 16 years drawn from a consumer panel representative of the Spanish population in this age group, over the course of a full week of broadcasting in February 2022. The sample was obtained through stratified random sampling by Autonomous Region, with quotas being set by reference to socio-demographic variables. Exposure was measured with an audiometer, and the nutrient content of the food and drink advertised was analysed using the nutrient profile of the WHO Regional Office for Europe. We used the Chi-squared test to analyse possible differences in advertising coverage by socio-economic level.

Results

The participants saw a weekly mean of 82.4 food and drink commercials, 67.4 of which were for unhealthy products (81.8%), mostly outside the child-protection time slot. On average, low-social class participants received 94.4% more impacts from unhealthy food and drink advertising than did high-class participants (99.9 vs. 51.4 respectively). The mean advertising coverage of unhealthy foods and drinks was 71.6% higher in low-class than in high-class participants (10.9% vs. 18.7%; p = 0.01).

Conclusion

Spanish children and adolescents received an average of 10 impacts per day from television spots for unhealthy foods and drinks. The exposure of low-class children is double that of high-class children, a finding compatible with the high prevalence of childhood obesity in Spain and the related socio-economic inequalities. To protect Spanish minors from the harmful effects of food advertising and reduce the related social health inequalities would require the implementation of a 24:00 watershed for unhealthy food advertising on television.
Ten-year association between change in speech-in-noise recognition and falls due to balance problems: a longitudinal cohort study
Authors: Jansen Lotte A. , van Wier Marieke F. , Vernimmen Freek P. J. , Goderie Thadé , van de Berg Raymond , Lemke Ulrike , Lissenberg-Witte Birgit I. , Kramer Sophia E.
Published: March 2024

Background

This study examined the relationship between speech-in-noise recognition and incident/recurrent falls due to balance problems ten years later (RQ-1); 10-year change in speech-in-noise recognition and falls (RQ-2a), as well as the role of dizziness in this relationship (RQ-2b). The association between hearing aid use and falls was also examined (RQ-3).

Methods

Data was collected from the Netherlands Longitudinal Study on Hearing between 2006 and December 2022. Participants completed an online survey and digits-in-noise test every five years. For this study, data was divided into two 10-year follow-up time intervals: T0 (baseline) to T2 (10-year follow-up), and T1 (5-years) to T3 (15-years). For all RQs, participants aged ≥ 40 years at baseline, without congenital hearing loss, and non-CI users were eligible (n = 592). Additionally, for RQ-3 participants with a speech reception threshold in noise (SRTn) ≥ -5.5 dB signal-to-noise ratio were included (n = 422). Analyses used survey variables on hearing, dizziness, falls due to balance problems, chronic health conditions, and psychosocial health. Logistic regressions using General Estimating Equations were conducted to assess all RQs.

Results

Among individuals with obesity, those with poor baseline SRTn had a higher odds of incident falls ten years later (odds ratio (OR):14.7, 95% confidence interval (CI) [2.12, 103]). A 10-year worsening of SRTn was significantly associated with a higher odds of recurrent (OR: 2.20, 95% CI [1.03, 4.71]) but not incident falls. No interaction was found between dizziness and change in SRTn. Hearing aid use (no use/ < 2 years use vs. ≥ 2 years) was not significantly associated with incident nor recurrent falls. Although there was a significant interaction with sex for this association, the effect of hearing aid use on incident/recurrent falls was not statistically significant among males nor females.

Conclusions

A longitudinal association between the deterioration in SRTn and recurrent falls due to balance problems after 10 years was confirmed in this study. This result stresses the importance of identifying declines in hearing earlier and justifies including hearing ability assessments within fall risk prevention programs. Mixed results of hearing aid use on fall risk warrant further investigation into the temporality of this association and possible differences between men and women.
Community-based rehabilitation services implemented by multidisciplinary teams among adults with stroke: a scoping review with a focus on Chinese experience
Authors: An Zifen , Li Ke , Yang Xinyi , Ke Jie , Xu Yuying , Zhang Xi , Meng Xianmei , Luo Xianwu , Yu Liping
Published: March 2024

Background

Despite the growing interest in hospital rehabilitation services for communities, studies on existing community-based rehabilitation (CBR) services remain scarce owing to limitations in the development of community health services and regional cultural diversity. As a guaranteed measure for ensuring the quality of rehabilitation services and achieving the desired service outcomes, clear roles and responsibilities in multidisciplinary teams and effective service delivery are particularly important.

Objective

This scoping review aimed to determine the scope of community stroke rehabilitation programs involving existing multidisciplinary teams and to analyze the implementation content and implementers’ functional roles to provide guidance for future CBR programs.

Methods

The scoping review design followed the methodology of the Joanna Briggs Institute and was based on the normative scoping review framework proposed by Arksey and O’Malley. The comprehensive CBR framework was proposed by World Health Organization-guided data charting and analysis.

Results

Of the 22,849 identified citations, 74 studies were included, consisting of 6,809 patients with stroke and 49 primary caregivers, most of whom were from China. The most common working mode in CBR programs was a dual approach involving both healthcare professionals in medical institutions and community healthcare professionals. The number of programs in each discipline was in the following descending order: nursing, medical care, rehabilitation, psychology, nutrition, and public health. Among these, multidisciplinary teams comprising medical, nursing, and rehabilitation disciplines were the most common, with a total of 29 programs. Disciplinary members were mainly responsible for implementing their respective disciplinary content, with physicians providing guidance for the programs. More than 82.4% of the studies reported 2–4 intervention strategies. The intervention forms of rehabilitation content were the most diverse, whereas preventive interventions were more homogeneous than others. Physical function and socio-psychological measurements were the most commonly reported outcomes.

Conclusion

CBR services implemented by multidisciplinary teams can effectively achieve functional and emotional improvement in patients with stroke, and nurses are the most involved in implementation, especially in community settings. The results further emphasize the importance of strengthening the exploration of nurses’ maximum potential to implement CBR plans in future practice.

Trial registration

The registration information for this scoping review can be found at osf.io/pv7tg.
Periodontal ligament stem cell-derived exosome-loaded Emodin mediated antimicrobial photodynamic therapy against cariogenic bacteria
Authors: Pourhajibagher Maryam , Bahador Abbas
Published: March 2024

Background

This study was conducted to investigate the efficiency of periodontal ligament (PDL) stem cell-derived exosome-loaded Emodin (Emo@PDL-Exo) in antimicrobial photodynamic therapy (aPDT) on Streptococcus mutans and Lactobacillus acidophilus as the cariogenic bacteria.

Materials and methods

After isolating and characterizing PDL-Exo, the study proceeded to prepare and verify the presence of Emo@PDL-Exo. The antimicrobial effect, anti-biofilm activity, and anti-metabolic potency of Emo, PDL-Exo, and Emo@PDL-Exo were then evaluated with and without irradiation of blue laser at a wavelength of 405 ± 10 nm with an output intensity of 150 mW/cm2 for a duration of 60 s. In addition, the study assessed the binding affinity of Emodin with GtfB and SlpA proteins using in silico molecular docking. Eventually, the study examined the generation of endogenous reactive oxygen species (ROS) and changes in the gene expression levels of gelE and sprE.

Results

The study found that using Emo@PDL-Exo-mediated aPDT resulted in a significant decrease in L. acidophilus and S. mutans by 4.90 ± 0.36 and 5.07 log10 CFU/mL, respectively (P < 0.05). The study found that using Emo@PDL-Exo for aPDT significantly reduced L. acidophilus and S. mutans biofilms by 44.7% and 50.4%, respectively, compared to untreated biofilms in the control group (P < 0.05). Additionally, the metabolic activity of L. acidophilus and S. mutans decreased by 58.3% and 71.2%, respectively (P < 0.05). The molecular docking analysis showed strong binding affinities of Emodin with SlpA and GtfB proteins, with docking scores of -7.4 and -8.2 kcal/mol, respectively. The study also found that the aPDT using Emo@PDL-Exo group resulted in the most significant reduction in gene expression of slpA and gtfB, with a decrease of 4.2- and 5.6-folds, respectively, compared to the control group (P < 0.05), likely due to the increased generation of endogenous ROS.

Discussion

The study showed that aPDT using Emo@PDL-Exo can effectively reduce the cell viability, biofilm activity, and metabolic potency of S. mutans and L. acidophilus. aPDT also significantly reduced the expression levels of gtfB and slpA mRNA due to the increased endogenous ROS generation. The findings suggest that Emo@PDL-Exo-mediated aPDT could be a promising antimicrobial approach against cariogenic microorganisms.
Quantitative analysis of the effect of docetaxel-induced edema on quality of life in patients with breast cancer and related factors: a prospective cohort study
Authors: Izawa Tomoko , Kobayashi Ami , Kawashima Masahiro , Kawaguchi-Sakita Nobuko , Nakakura Akiyoshi , Kataoka Yuki , Shide Kenichiro , Mori Yukiko , Yamazaki Kazuhiro , Toi Masakazu , Arao Harue
Published: March 2024

Background

Systemic edema is an adverse effect of docetaxel chemotherapy and causes distress to patients, including those receiving this agent for breast cancer. However, its characteristics and factors related to its effect on quality of life (QoL) have not been adequately investigated. In this study, we assessed systemic edema quantitatively, explored related factors, and evaluated QoL in patients receiving docetaxel for breast cancer.

Methods

The study had a prospective cohort design and included 37 patients with no known history of swelling who were treated with docetaxel between September 2019 and April 2022. Patients were examined at the start, middle, and end of their course of treatment and 1 and 2 months later. Body water content, body mass, fat mass, and muscle mass were quantified using bioelectrical impedance analysis. Systemic edema was evaluated with reference to the Common Terminology Criteria for Adverse Events. The timing of development of systemic edema at any anatomical site that was grade 2 or worse was recorded. QoL was assessed using the Quality of Life-Anti Cancer Drug scale. Nutrition was evaluated using the Brief-type self-administered diet history questionnaire. Multivariable logistic regression analysis was performed to identify related factors. QoL was also compared between patients with edema and those without edema.

Results

Systemic edema developed in 67% of the study participants and was most prevalent at the end of treatment. Body fat mass (adjusted odds ratio [aOR] 0.802, 95% confidence interval [CI] 0.651–0.988, p = 0.038), disease stage (aOR 3.279, 95% CI 0.493–21.793, p = 0.219), and history of alcohol consumption (aOR 0.141, 95% CI 0.013–1.521, p = 0.106) were identified as risk factors for docetaxel-induced edema. Participants who developed systemic edema experienced more physical, vital, and emotional distress 1 month after treatment than those who did not. There was no association between systemic edema and nutrition.

Conclusions

Systemic edema may develop after treatment with docetaxel and increase distress in patients with a high body fat mass. Patients at risk of systemic edema should be informed in advance about the potential frequency, location, and timing of its onset and encouraged to self-manage this condition.
A blueprint for success: lessons learned from developing the official guide to Iranian undergraduate medical education accreditation
Authors: Aghabagheri Mahdi , Sabet Babak , Heidarzadeh Abtin , Kalantar Ebrahim , Norouzi Ali , Alizadeh Maryam
Published: March 2024

We are excited to contribute our thoughts and insights to the discussion initiated by Gandomkar et al. in their article on the accreditation system in Iran (Gandomkar et al., BMC Med Educ 23:379, 2023). As individuals who have been directly involved in the process of meta-accreditation and possess a comprehensive understanding of the various stages of Undergraduate Medical Education (UME) accreditation in Iran, we would like to highlight additional points that were identified through a rigorous hermeneutic phenomenology process proposed by Gadamer (Gadamer, Truth and Method, 2013) and offer a complementary point of view to the previous work. By sharing our insights, we hope to contribute to the ongoing discourse surrounding UME accreditation.
The role of human capital and stress for cost awareness in the healthcare system: a survey among German hospital physicians
Authors: Lüdemann Christoph , Gerken Maike , Hülsbeck Marcel
Published: March 2024

Background

Germany has the highest per capita health care spending among EU member states, but its hospitals face pressure to generate profits independently due to the government’s withdrawal of investment cost coverage. The diagnosis related groups (DRG) payment system was implemented to address the cost issue, challenging hospital physicians to provide services within predefined prices and an economic target corridor to reduce costs. This study examines the extent of cost awareness among medical personnel in German hospitals and its influencing factors.

Methods

We developed an online survey in which participants across all specialties in hospitals estimated the prices in euros of four common interventions and answered questions about their human capital and perceived stress on the workplace. As a measure of cost awareness, we used the probability of estimating the prices correctly within a reasonable margin. We employed logit logistic regression estimators to identify influencing factors in a sample of 86 participants.

Results

The results revealed that most of the respondents were unaware of the costs of common interventions. General human capital, acquired through prior education, and job-specific human capital had no influence on cost awareness, whereas domain-specific human capital, that is, gaining economic knowledge based on self-interest, had a positive nonlinear effect on cost awareness. Furthermore, an increased stress level negatively influenced cost awareness.

Conclusions

This paper is the first of its kind for the German health care sector that contributes responses to the question whether health care professionals in German hospitals have cost awareness and if not, what reasons lie behind this lack of knowledge. Our findings show that the cost awareness desired by the introduction of the DRG system has yet to be achieved by medical personnel.
Introgressions lead to reference bias in wheat RNA-seq analysis
Authors: Coombes Benedict , Lux Thomas , Akhunov Eduard , Hall Anthony
Published: March 2024

Background

RNA-seq is a fundamental technique in genomics, yet reference bias, where transcripts derived from non-reference alleles are quantified less accurately, can undermine the accuracy of RNA-seq quantification and thus the conclusions made downstream. Reference bias in RNA-seq analysis has yet to be explored in complex polyploid genomes despite evidence that they are often a complex mosaic of wild relative introgressions, which introduce blocks of highly divergent genes.

Results

Here we use hexaploid wheat as a model complex polyploid, using both simulated and experimental data to show that RNA-seq alignment in wheat suffers from widespread reference bias which is largely driven by divergent introgressed genes. This leads to underestimation of gene expression and incorrect assessment of homoeologue expression balance. By incorporating gene models from ten wheat genome assemblies into a pantranscriptome reference, we present a novel method to reduce reference bias, which can be readily scaled to capture more variation as new genome and transcriptome data becomes available.

Conclusions

This study shows that the presence of introgressions can lead to reference bias in wheat RNA-seq analysis. Caution should be exercised by researchers using non-sample reference genomes for RNA-seq alignment and novel methods, such as the one presented here, should be considered.
Characterization and trajectories of hematological parameters prior to severe COVID-19 based on a large-scale prospective health checkup cohort in western China: a longitudinal study of 13-year follow-up
Authors: Lin Yifei , Yang Yong , Xiang Nanyan , Wang Le , Zheng Tao , Zhuo Xuejun , Shi Rui , Su Xiaoyi , Liu Yan , Liao Ga , Du Liang , Huang Jin
Published: March 2024

Background

The relaxation of the “zero-COVID” policy on Dec. 7, 2022, in China posed a major public health threat recently. Complete blood count test was discovered to have complicated relationships with COVID-19 after the infection, while very few studies could track long-term monitoring of the health status and identify the characterization of hematological parameters prior to COVID-19.

Methods

Based on a 13-year longitudinal prospective health checkup cohort of ~ 480,000 participants in West China Hospital, the largest medical center in western China, we documented 998 participants with a laboratory-confirmed diagnosis of COVID-19 during the 1 month after the policy. We performed a time-to-event analysis to explore the associations of severe COVID-19 patients diagnosed, with 34 different hematological parameters at the baseline level prior to COVID-19, including the whole and the subtypes of white and red blood cells.

Results

A total of 998 participants with a positive SARS-CoV-2 test were documented in the cohort, 42 of which were severe cases. For white blood cell-related parameters, a higher level of basophil percentage (HR = 6.164, 95% CI = 2.066–18.393, P = 0.001) and monocyte percentage (HR = 1.283, 95% CI = 1.046–1.573, P = 0.017) were found associated with the severe COVID-19. For lymphocyte-related parameters, a lower level of lymphocyte count (HR = 0.571, 95% CI = 0.341–0.955, P = 0.033), and a higher CD4/CD8 ratio (HR = 2.473, 95% CI = 1.009–6.059, P = 0.048) were found related to the risk of severe COVID-19. We also observed that abnormality of red cell distribution width (RDW), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin might also be involved in the development of severe COVID-19. The different trajectory patterns of RDW-SD and white blood cell count, including lymphocyte and neutrophil, prior to the infection were also discovered to have significant associations with the risk of severe COVID-19 (all P < 0.05).

Conclusions

Our findings might help decision-makers and clinicians to classify different risk groups of population due to outbreaks including COVID-19. They could not only optimize the allocation of medical resources, but also help them be more proactive instead of reactive to long COVID-19 or even other outbreaks in the future.
Camrelizumab plus gemcitabine and oxaliplatin for relapsed or refractory classical Hodgkin lymphoma: a phase II trial
Authors: Liu Yanfei , Ping Lingyan , Song Yuqin , Tang Yongjing , Zheng Wen , Liu Weiping , Ying Zhitao , Zhang Chen , Wu Meng , Feng Feier , Lin Ningjing , Tu Meifeng , Zhu Jun , Xie Yan
Published: March 2024

Background

Classical Hodgkin lymphoma (cHL) is a highly curable disease, while novel therapy is needed for refractory or relapsed (R/R) patients. This phase II trial aimed to evaluate the role of camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in R/R cHL patients.

Methods

Transplant-eligible patients with R/R cHL were enrolled and received two 14-day cycles of camrelizumab 200 mg intravenously (IV) and two 28-day cycles of camrelizumab 200 mg IV, gemcitabine 1000 mg/m2 IV, and oxaliplatin 100 mg/m2 IV on days 1 and 15. Patients with partial response (PR) or stable disease received an additional cycle of combination therapy. Those who achieved complete response (CR) or PR proceeded to autologous stem cell transplantation (ASCT). The primary endpoint was the CR rate at the end of protocol therapy before ASCT.

Results

Forty-two patients were enrolled. At the end of protocol therapy, the objective response rate and CR rate were 94.9% (37/39) and 69.2% (27/39) in the evaluable set, and 88.1% (37/42) and 64.3% (27/42) in the full analysis set, respectively. Twenty-nine patients (69.0%) proceeded to ASCT, and 4 of 5 patients with PR achieved CR after ASCT. After a median follow-up of 20.7 months, the 12-month progression-free survival rate was 96.6% and the 12-month overall survival rate was 100%. Grade 3 or higher treatment emergent adverse events occurred in 28.6% of patients (12/42), mainly hematological toxicity.

Conclusions

Camrelizumab combined with GEMOX constitutes an effective salvage therapy for R/R cHL, proving to be relatively well-tolerated and facilitating ASCT in most patients, thus promoting sustained remission.

Trial registration

ClinicalTrials.gov NCT04239170. Registered on January 1, 2020.
Effect of soy isoflavone supplementation on blood pressure: a meta-analysis of randomized controlled trials
Authors: Lei Lifu , Hui Suocheng , Chen Yushi , Yan Hongjia , Yang Jian , Tong Shiwen
Published: March 2024

Background

Previous experimental studies have suggested that the consumption of soy isoflavones may have a potential impact on lowering blood pressure. Nevertheless, epidemiological studies have presented conflicting outcomes concerning the correlation between soy isoflavone consumption and blood pressure levels. Consequently, a comprehensive meta-analysis of all eligible randomized controlled trials (RCTs) was conducted to explore the influence of soy isoflavones on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in adults.

Methods

A thorough search of PubMed, Embase, and the Cochrane Library for relevant literature up to April 30, 2023 was conducted. RCTs involving adults that compared soy isoflavone supplementation with a placebo (the same matrix devoid of soy isoflavone) were included. The combined effect size was presented as the weighted mean difference (WMD) along with 95% confidence interval (CI), employing a fixed-effects model.

Results

Our meta-analysis included a total of 24 studies involving 1945 participants. The results revealed a significant reduction in both SBP and DBP with soy isoflavone supplementation. Subgroup analyses suggested more pronounced reductions in SBP and DBP for interventions lasting ≥6 months, in individuals receiving mixed-type soy isoflavone, and among patients with metabolic syndrome or prehypertension. However, we did not detect significant nonlinear associations between supplementation dosage and intervention duration concerning both SBP and DBP. The overall quality of evidence was deemed moderate.

Conclusions

The current meta-analysis revealed that supplementation with soy isoflavones alone effectively reduces blood pressure. Additional high-quality studies are required to investigate the efficacy of blood pressure reduction through supplementation with an optimal quantity and proportion of soy isoflavone.
CD73/adenosine axis exerts cardioprotection against hypobaric hypoxia-induced metabolic shift and myocarditis in a sex-dependent manner
Authors: Ndzie Noah Marie Louise , Mprah Richard , Wowui Prosperl Ivette , Adekunle Adebayo Oluwafemi , Adu-Amankwaah Joseph , Tan Rubin , Gong Zheng , Li Tao , Fu Lu , Machuki Jeremiah Ong’achwa , Zhang Shijie , Sun Hong
Published: March 2024

Background

Clinical and experimental studies have shown that the myocardial inflammatory response during pathological events varies between males and females. However, the cellular and molecular mechanisms of these sex differences remain elusive. CD73/adenosine axis has been linked to anti-inflammatory responses, but its sex-specific cardioprotective role is unclear. The present study aimed to investigate whether the CD73/adenosine axis elicits sex-dependent cardioprotection during metabolic changes and myocarditis induced by hypobaric hypoxia.

Methods

For 7 days, male and female mice received daily injections of the CD73 inhibitor adenosine 5′- (α, β-methylene) diphosphate (APCP) 10 mg/kg/day while they were kept under normobaric normoxic and hypobaric hypoxic conditions. We evaluated the effects of hypobaric hypoxia on the CD73/adenosine axis, myocardial hypertrophy, and cardiac electrical activity and function. In addition, metabolic homeostasis and immunoregulation were investigated to clarify the sex-dependent cardioprotection of the CD73/adenosine axis.

Results

Hypobaric hypoxia-induced cardiac dysfunction and adverse remodeling were more pronounced in male mice. Also, male mice had hyperactivity of the CD73/adenosine axis, which aggravated myocarditis and metabolic shift compared to female mice. In addition, CD73 inhibition triggered prostatic acid phosphatase ectonucleotidase enzymatic activity to sustain adenosine overproduction in male mice but not in female mice. Moreover, dual inhibition prostatic acid phosphatase and CD73 enzymatic activities in male mice moderated adenosine content, alleviating glycolytic shift and proinflammatory response.

Conclusion

The CD73/adenosine axis confers a sex-dependent cardioprotection. In addition, extracellular adenosine production in the hearts of male mice is influenced by prostatic acid phosphatase and tissue nonspecific alkaline phosphatase.
Enhancing cardiometabolic health: unveiling the synergistic effects of high-intensity interval training with spirulina supplementation on selected adipokines, insulin resistance, and anthropometric indices in obese males
Authors: Delfan Maryam , Saeidi Ayoub , Supriya Rashmi , Escobar Kurt A , Laher Ismail , Heinrich Katie M. , Weiss Katja , Knechtle Beat , Zouhal Hassane
Published: March 2024

This study investigated the combined effects of 12 weeks of high-intensity interval training (HIIT) and spirulina supplementation on adipokine levels, insulin resistance, anthropometric indices, and cardiorespiratory fitness in 44 obese males (aged 25–40 years). The participants were randomly assigned to one of four groups: control (CG), supplement (SG), training (TG), or training plus supplement (TSG). The intervention involved daily administration of either spirulina or a placebo and HIIT three times a week for the training groups. Anthropometric indices, HOMA-IR, VO2peak, and circulating adipokines (asprosin and lipocalin2, omentin-1, irisin, and spexin) were measured before and after the 12-week intervention. Post-intervention analysis indicated differences between the CG and the three interventional groups for body weight, fat-free mass (FFM), percent body fat (%BF), HOMA-IR, and adipokine levels (p < 0.05). TG and SG participants had increased VO2peak (p < 0.05). Spirulina supplementation with HIIT increased VO2peak, omentin-1, irisin, and spexin, while causing decreases in lipocalin-2 and asprosin levels and improvements in body composition (weight, %fat), BMI, and HOMA-IR. Notably, the combination of spirulina and HIIT produced more significant changes in circulating adipokines and cardiometabolic health in obese males compared to either supplementation or HIIT alone (p < 0.05). These findings highlight the synergistic benefits of combining spirulina supplementation with HIIT, showcasing their potential in improving various health parameters and addressing obesity-related concerns in a comprehensive manner.
Cryptotanshinone inhibits PFK-mediated aerobic glycolysis by activating AMPK pathway leading to blockade of cutaneous melanoma
Authors: Chen Qiong , Liu Yang , Zhu Yunxuan , Zhu Ziyan , Zou Jueyao , Pan Yanhong , Lu Yin , Chen Wenxing
Published: March 2024

Background

Cutaneous melanoma is a kind of skin malignancy with low morbidity but high mortality. Cryptotanshinone (CPT), an important component of salvia miltiorrhiza has potent anti-tumor activity and also indicates therapeutic effect on dermatosis. So we thought that CPT maybe a potential agent for therapy of cutaneous melanoma.

Methods

B16F10 and A375 melanoma cells were used for in vitro assay. Tumor graft models were made in C57BL/6N and BALB/c nude mice for in vivo assay. Seahorse XF Glycolysis Stress Test Kit was used to detect extracellular acidification rate and oxygen consumption rate. Si-RNAs were used for knocking down adenosine monophosphate-activated protein kinase (AMPK) expression in melanoma cells.

Results

CPT could inhibit the proliferation of melanoma cells. Meanwhile, CPT changed the glucose metabolism and inhibited phosphofructokinase (PFK)-mediated glycolysis in melanoma cells to a certain extent. Importantly, CPT activated AMPK and inhibited the expression of hypoxia inducible factor 1α (HIF-1α). Both AMPK inhibitor and silencing AMPK could partially reverse CPT’s effect on cell proliferation, cell apoptosis and glycolysis. Finally, in vivo experimental data demonstrated that CPT blocked the growth of melanoma, in which was dependent on the glycolysis-mediated cell proliferation.

Conclusions

CPT activated AMPK and then inhibited PFK-mediated aerobic glycolysis leading to inhibition of growth of cutaneous melanoma. CPT should be a promising anti-melanoma agent for clinical melanoma therapy.
A multi-center cross-sectional study of Chinese Herbal Medicine-Drug adverse reactions using active surveillance in Singapore’s Traditional Chinese Medicine clinics
Authors: Ng Chester Yan Jie , Zhao Yan , Wang Ning , Chia Kwan Leung , Teo Chun Huat , Peh William , Yeo Pansy , Zhong Linda L. D.
Published: March 2024

Background

This study aimed to investigate the rates and causality of patient-reported adverse events (AEs) associated with concomitant Chinese Herbal Medicine (CHM) and Western Medicine prescription drug (WMPD) consumption through active surveillance in Singapore’s Traditional Chinese Medicine (TCM) clinics.

Methods

A cross-sectional study was conducted at five TCM clinics across Singapore from 8th May till 8th July 2023. Patients were screened to determine rates of CHM and WMPD consumption, and then interviewed if an AE was reported. An expert committee assessed the AE reports to determine causality. Along with descriptive statistics, odds ratios were calculated to determine AE occurrence likelihoods for patients who consumed both CHM and WMPD compared to CHM consumption alone.

Results

1028 patients were screened and 62.65% of them reported concurrent CHM-WMPD consumption. Patients who consumed CHM and WMPD were 3.65 times more likely to experience an AE as compared to CHM consumption alone. 18 AE reports were adjudicated, with most AEs deemed unlikely due to CHM consumption.

Conclusions

A large proportion of patients consumed CHM and WMPD concurrently, thus increasing their risk of experiencing AEs compared to those consuming CHM only. Active surveillance is applicable for detecting AEs, collecting data for causality assessment, and analysis.
Analysis of caregiver perspectives on patients with mucopolysaccharidosis II treated with pabinafusp alfa: results of qualitative interviews in Japan
Authors: Nakamura Kimitoshi , Sakai Norio , Hossain Mohammad Arif , Eisengart Julie B , Yamamoto Tatsuyoshi , Tanizawa Kazunori , So Sairei , Schmidt Mathias , Sato Yuji
Published: March 2024

Background

Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a rare X-linked metabolic disorder predominantly affecting males. Pabinafusp alfa, an iduronate-2-sulfatase enzyme designed to cross the blood-brain barrier, was approved in Japan in 2021 as the first enzyme replacement therapy targeting both the neuropathic and somatic signs and symptoms of MPS II. This study reports caregivers’ experiences of MPS II patients receiving pabinafusp alfa through qualitative interviews.

Methods

Semi-structured, qualitative interviews were conducted with caregivers at seven clinical sites in Japan using a semi-structured moderation guide (Voice of the Caregiver guide). Thematic analysis was applied to the interview transcripts to identify symptoms and health-related quality of life impacts at baseline, changes during treatment, and overall treatment experience.

Results

Seven caregivers from 16 trial sites participated, representing seven children aged 8–18 years who had received pabinafusp alfa for 3.3–3.5 years at the time of the interviews. Data suggest a general trend toward improvement in multiple aspects, although not all caregivers observed discernible changes. Reported cognitive improvements included language skills, concentration, self-control, eye contact, mental clarity, concept understanding, following instructions, and expressing personal needs. Further changes were reported that included musculoskeletal improvements and such somatic changes as motor function, mobility, organ involvement, joint mobility, sleep patterns, and fatigue. Four caregivers reported improvements in family quality of life, five expressed treatment satisfaction, and all seven indicated a strong willingness to continue treatment of their children with pabinafusp alfa.

Conclusion

Caregivers’ perspectives in this study demonstrate treatment satisfaction and improvement in various aspects of quality of life following therapy with pabinafusp alfa. These findings enhance understanding of pabinafusp alfa’s potential benefits in treating MPS II and contribute to defining MPS II-specific outcome measures for future clinical trials.
Can computer simulation support strategic service planning? Modelling a large integrated mental health system on recovery from COVID-19
Authors: Pierotti Livia , Cooper Jennifer , James Charlotte , Cassels Kenah , Gara Emma , Denholm Rachel , Wood Richard
Published: March 2024

Background

COVID-19 has had a significant impact on people’s mental health and mental health services. During the first year of the pandemic, existing demand was not fully met while new demand was generated, resulting in large numbers of people requiring support. To support mental health services to recover without being overwhelmed, it was important to know where services will experience increased pressure, and what strategies could be implemented to mitigate this.

Methods

We implemented a computer simulation model of patient flow through an integrated mental health service in Southwest England covering General Practice (GP), community-based ‘talking therapies’ (IAPT), acute hospital care, and specialist care settings. The model was calibrated on data from 1 April 2019 to 1 April 2021. Model parameters included patient demand, service-level length of stay, and probabilities of transitioning to other care settings. We used the model to compare ‘do nothing’ (baseline) scenarios to ‘what if’ (mitigation) scenarios, including increasing capacity and reducing length of stay, for two future demand trajectories from 1 April 2021 onwards.

Results

The results from the simulation model suggest that, without mitigation, the impact of COVID-19 will be an increase in pressure on GP and specialist community based services by 50% and 50–100% respectively. Simulating the impact of possible mitigation strategies, results show that increasing capacity in lower-acuity services, such as GP, causes a shift in demand to other parts of the mental health system while decreasing length of stay in higher acuity services is insufficient to mitigate the impact of increased demand.

Conclusion

In capturing the interrelation of patient flow related dynamics between various mental health care settings, we demonstrate the value of computer simulation for assessing the impact of interventions on system flow.
Distribution of blood lead and cadmium levels in healthy children aged 0 to 18 years and analysis of related influencing factors in Henan, China: data findings from 2017 to 2022
Authors: Yan Hui , Zhai Bo , Feng Ruiling , Wang Penggao , Yang Fang , Zhou Yang
Published: March 2024

Background

There is still a lack of data on blood lead levels (BLLs) and blood lead levels (BLLs) in healthy children of all ages from 0 to 18 years in China. This study was performed to analyze the BLLs and BCLs in healthy children aged 0-18 years from 2017 to 2022 in urban and rural areas of Henan Province, Central China, as well as their relationships with socio-demographic variables and certain relevant exposure factors. To provide a basis for evaluating public health policy development and exposure risk management.

Methods

This was an observational study containing data from 17 prefecture-level cities in Henan, China. Blood Pb and Cd levels were determined using a triple quadrupole inductively coupled plasma mass spectrometer equipped with an autosampler. We first calculated the concentrations of Pb and Cd elements in participants of different genders, ages and years, and then created visual graphs depicting the distribution of each element in terms of gender, age and year (2017-2022). The rates between different groups were compared using the Chi-square test or Fisher exact test (if applicable). The means were compared by one-way ANOVA, medians were compared with the Kruskal-Wallis rank-sum test. Generalized linear models (GLM) were performed to estimate the effects of various factors on blood Pb and Cd concentrations in children.

Results

We recruited a total of 25,920 children (16,142 boys and 9,778 girls) aged 0.01 to 18.00 years (2.58 (1.00,6.25)). The median of BLLs was 23.48µg/L, around 9.39% of studied children had elevated BLLs. The median of BCLs was 0.66µg/L, around 1.84% of studied children had elevated BCLs. The median blood Pb concentration was higher in boys (23.90µg/L) than in girls (22.75µg/L) (P<0.001). The median blood Pb concentration was highest in the 3-7 years group (24.51µg/L) and the median blood Cd concentration was highest in the 1-3 years group (0.66µg/L) among all age groups. Both BLLs and BCLs were substantially higher in children in 2020-2022 compared to 2017-2019. Rural children had lower BLLs and higher BCLs. The results of the generalized linear model showed that children in households using Oil, coal, pellet or other wood as a fuel for heating, children with higher frequency of exposure to tobacco smoke and beverage intake had significantly increased chances of elevated BLLs and BCLs.

Conclusions

Pb and Cd exposure of children in this area is relatively low, but associated risk factors continue to exist in vulnerable populations. This study is the first big data analysis of Pb and Cd in children in Henan, China, and provides baseline information for future research.
Respiratory syncytial virus-associated hospitalizations among children: an Italian retrospective observational study
Authors: Fortunato Francesca , Campanozzi Angelo , Maffei Gianfranco , Arena Fabio , Carri Valeria Delli , Rollo Tiziana , Lopalco Pier Luigi , Martinelli Domenico
Published: March 2024

Background

Respiratory syncytial virus (RSV), a single-stranded RNA virus, is a leading cause of hospitalization in infants, especially ≤ 2 months of life. In the light new immunization strategies adoption, we described epidemiological and clinical characteristics of RSV-associated hospitalizations in pediatric and neonatal intensive care units of the Policlinico Foggia Hospital, Apulia Region, Italy.

Methods

Hospitalized children with a laboratory-confirmed RSV infection from 2011 to 2023 were retrospectively evaluated. Clinical information was collected from Hospital Discharge Registry in the period 2011–2020. The proportion of the hospitalization for acute respiratory infections (ARIs) associated to RSV was calculated and the hospitalization cost was analyzed by using the diagnosis-related group reimbursement rate. The anticipated impact of immunization either with monoclonal antibodies or maternal immunization on the number of hospitalizations was estimated. All analyses and quality assessment were performed using STATA/SE15.0.

Results

A total of 1,005 RSV-cases were included in the study, of which 86.3% occurred between December-March. In the period 2011–2020, 832 RSV-cases were matched with the corresponding hospital admissions; 75.2% were aged < 1 year (49.6% 0–2 months). Bronchiolitis was the most frequent admission diagnosis occurring in 63.3% of patients; 25% of children were affected by a very severe RSV-disease. Younger age ≤ 2 months (OR:14.8, 95%CI:8.30–26.31, p = 0.000), higher length-of-hospital-stay (OR:1.01, 95%CI:1.0–1.02, p = 0.030) and history of prematurity (OR:4.4, 95%CI:1.57–12.11, p = 0.005) were associated with a higher disease severity. RSV caused 48.9% of ARIs among children < 1 year. The mean cost of an RSV-associated hospitalization was 3,036 euros/year, with the higher cost in the 0–2 months age group (4,225 euros/year). Immunization programs with nirsevimab could prevent 51.4 RSV hospitalizations/year and 18.1 very severe RSV disease/year in infants < 1 year of age. RSV vaccine could prevent 46.1 of hospitalizations/year caused by RSV within 180 days after birth.

Conclusions

Our study contributes to outlining the baseline profile of RSV-associated hospitalizations among Italian children by providing epidemiological/clinical/economic estimates. While awaiting new recommendations on immunization, healthcare-workers should persist in implementing public health measures and appropriate case management to control RSV seasonal epidemics. Strengthened laboratory RSV surveillance is needed to inform the implementation of the new immunization strategies.
Healthcare migration in Italian paediatric haematology-oncology centres belonging to AIEOP
Authors: Rondelli Roberto , Belotti Tamara , Masetti Riccardo , Locatelli Franco , Massimino Maura , Biffi Alessandra , Dufour Carlo , Fagioli Franca , Menna Giuseppe , Biondi Andrea , Favre Claudio , Zecca Marco , Santoro Nicola , Russo Giovanna , Perrotta Silverio , Pession Andrea , Prete Arcangelo
Published: March 2024

Background

In Italy, there is a network of centres headed by the Italian Association of Pediatric Hematology and Oncology (AIEOP) for the diagnosis and treatment of paediatric cancers on almost the entire national territory.

Nevertheless, migration of patients in a hospital located in a region different from that of residence is a widespread habit, sometimes motivated by several reasons.

The aim of this paper is to assess the impact of migration of children with cancer to AIEOP centres in order to verify their optimal distribution throughout the national territory.

Methods

To this purpose, we used information on 41,205 registered cancer cases in the database of Mod.1.01 Registry from AIEOP centres, with age of less than 20 years old at diagnosis, diagnosed from 1988 to 2017.

Patients’ characteristics were analysed and compared using the X2 or Fisher’s exact test or Mann–Whitney test, when appropriate.

Survival distributions were estimated using the method of Kaplan and Meier, and the log-rank test was used to examine differences among subgroups.

Results

Extra-regional migration involved overall 19.5% of cases, ranging from 23.3% (1988–1997) to 16.4% (2008–2017) (p < 0.001).

In leukaemias and lymphomas we observed a mean migration of 8.8% overall, lower in the North (1.2%) and Centre (7.8%) compared to the South & Isles (32.3%).

In the case of solid tumours, overall migration was 25.7%, with 4.2% in the North, 17.2% in the Centre and 59.6% in the South & Isles.

For regions with overall levels of migration higher than the national average, most migration cases opted for AIEOP centres of close or even neighbouring regions.

Overall survival at 10 years from diagnosis results 69.9% in migrants vs 78.3% in no migrants (p < 0.001).

Conclusions

There is still a certain amount of domestic migration, the causes of which can be easily identified: migration motivated by a search for high specialization, migration due to lack of local facilities, or regions in which no AIEOP centres are present, which makes migration obligatory.

Better coordination between AIEOP centres could help to reduce so-called avoidable migration, but technical and political choices will have to be considered, with the active participation of sector technicians.