bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractThis 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

Abstract
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

Abstract
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

Abstract
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

Abstract

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.