bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Loneliness is a monotonous thing”: descriptive qualitative research on the loneliness of caring relatives
Authors: Chistell Flurina , Stängle Sabrina , Fringer André 
Published: May 2023

Abstract
Background
The phenomenon of loneliness is increasing worldwide. Caring relatives (CRs) are at high risk of suffering from loneliness. Although some studies have already investigated the issue of loneliness among CRs, there is a lack of evidence to help understand the experience of loneliness in depth. The aim of this study is to record and analyse the experience of loneliness among CRs of chronically ill people. Specifically, the aim is to develop a conceptual model based on the concepts of social, emotional, and existential loneliness.

Methodology
A qualitative-descriptive research design with narrative semistructured interviews was chosen. Thirteen CRs—three daughters, six wives and four husbands—participated in the study. The participants were an average of 62.5 years old. The interviews took place from September 2020 to January 2021 and lasted an average of 54 min. The data were analysed inductively using coding. The analysis was carried out in the following three coding phases: initial open coding, axial coding, and selective coding. The central phenomenon was abductively generated from the main categories.

Results
A chronic illness gradually changes the participants’ normal lives over time. A feeling of social loneliness is experienced, as their quality of social contacts no longer meets their needs. Thoughts about the future and the question of why are omnipresent can create a feeling of existential loneliness. Lack of communication in the partnership or in the family relationship, the changed personality of the ill person as well as the resulting role shift are stressful. Moments of closeness and tenderness become rare, and a change in togetherness takes place. In such moments, there is a strong feeling of emotional loneliness. Personal needs rapidly fade into the background. One’s own life comes to a standstill. Accordingly, loneliness is perceived by the participants to be a stagnant life and is experienced as monotonous and painful. Feelings such as helplessness, powerlessness, frustration, anger, and sadness accompany this loneliness.

Conclusion
The study results show that the feeling of loneliness is present and experienced in a similar way by CRs, regardless of age and relationship to an ill person and that a need for action must derive from this. With the conceptual model, it is possible to offer versatile starting points for nursing practice, such as sensitization, to foster further research into the topic.
Scaling-up problem management plus for refugees in Switzerland - a qualitative study
Authors: Spaaij Julia , Fuhr Daniela C. , Akhtar Aemal , Casanova Luisa , Klein Tobias , Schick Matthis , Weilenmann Sonja , Roberts Bayard , Morina Naser 
Published: May 2023

AbstractBackgroundRefugees are at an increased risk of developing symptoms of mental disorders but face various structural and socio-cultural barriers to accessing mental health care. The SPIRIT project (Scaling-up Psychological Interventions in Refugees In SwiTzerland) seeks to promote the resilience of refugees and improve their access to mental health care. For this purpose, Problem Management Plus (PM+), an evidence-based low-intensity psychological intervention delivered by trained non-specialist “helpers”, is being scaled-up in Switzerland.ObjectiveTo identify factors influencing the process of the large-scale implementation of PM + for refugees in Switzerland and to develop recommendations to guide the implementation process.Methods22 semi-structured interviews were conducted with key informants (Syrian refugees who previously participated in PM+, PM + helpers, health professionals working with refugees and decision-makers from the migration, integration, social, and health sectors). The data were analyzed using thematic analysis, combining an inductive and deductive approach.ResultsThe data revealed three major themes, which might have an impact for the longer-term implementation of PM + in Switzerland. First, preconditions for successful integration in the health system prior to scaling-up such as sustainable funding or the introduction of a stepped care approach. Second, the requirements for the PM + intervention supporting scale-up such as quality control during PM + delivery, PM + modality, time and setting when PM + is offered or the views on task sharing. Third, the perceived benefits of scaling-up PM + in Switzerland.ConclusionsOur results have shown that PM + must be scaled-up within a stepped care approach, including a functioning triage system and sustainable funding. Rather than selecting one modality or setting, it seemed preferable to offer a variety of formats and settings to achieve maximum reach and benefits. A successful scale-up of PM + in Switzerland might have various benefits. Communicating them to policy-makers and health providers, might enhance their acceptability of the intervention and their willingness to adopt PM + in regulatory structure and promote it.
Unexpectedly higher levels of anti-orthopoxvirus neutralizing antibodies are observed among gay men than general adult population
Authors: Feng Yanmeng , Zhang Yifan , Liu Shengya , Guo Meng , Huang Haojie , Guo Cuiyuan , Wang Wanhai , Zhang Wenhong , Tang Heng , Wan Yanmin 
Published: May 2023

AbstractBackgroundThe confirmed cases in the current outbreak of Monkeypox are predominantly identified in the networks of men who have sex with men (MSM). The preexisting antibodies may profoundly impact the transmission of monkeypox virus (MPXV), however the current-day prevalence of antibodies against MPXV among gay men is not well characterized.MethodsA cohort of gay men (n = 326) and a cohort of the general adult population (n = 295) were enrolled in this study. Binding antibodies responses against MPXV/vaccinia and neutralizing antibody responses against vaccinia virus (Tiantan strain) were measured. The antibody responses of these two cohorts were then compared, as well as the responses of individuals born before and in/after 1981 (when the smallpox vaccination ceased in China). Finally, the correlation between the anti-MPXV antibody responses and the anti-vaccinia antibody responses, and the associations between preexisting anti-orthopoxvirus antibody responses and the diagnosed sexually transmitted infections (STIs) in the MSM cohort were analyzed separately.ResultsOur data showed that binding antibodies against MPXV H3, A29, A35, E8, B6, M1 proteins and vaccinia whole-virus lysate could be detected in individuals born both before and in/after 1981, of which the prevalence of anti-vaccinia binding antibodies was significantly higher among individuals born before 1981 in the general population cohort. Moreover, we unexpectedly found that the positive rates of binding antibody responses against MPXV H3, A29, A35, E8 and M1 proteins were significantly lower among individuals of the MSM cohort born in/after 1981, but the positive rates of anti-MPXV B6 and anti-vaccinia neutralizing antibody responses were significantly higher among these individuals compared to those of age-matched participants in the general population cohort. Additionally, we demonstrated that the positive and negative rates of anti-MPXV antibody responses were associated with the anti-vaccinia antibody responses among individuals born before 1981 in the general population cohort, but no significant association was observed among individuals born in/after 1981 in both cohorts. The positive rates of both the binding and the neutralizing antibody responses were comparable between individuals with and without diagnosed STIs in the MSM cohort.ConclusionsAnti-MPXV and anti-vaccinia antibodies could be readily detected in an MSM cohort and a general population cohort. And a higher level of anti-vaccinia neutralizing antibody responses was observed among individuals who did not get vaccinated against smallpox in the MSM cohort compared to age-matched individuals in the general population cohort.
The identification of a two-gene prognostic model based on cisplatin resistance-related ceRNA network in small cell lung cancer
Authors: Zhang Yani , Zhu Qizhi , Qi Jian , Fu Meng , Xu Ao , Wang Wei , Wang Hongzhi , Nie Jinfu , Hong Bo 
Published: May 2023

Abstract
Background
Small cell lung cancer (SCLC) is a very malignant tumor with rapid growth and early metastasis. Platinum-based chemo-resistance is the major issue for SCLC treatment failure. Identifying a new prognostic model will help to make an accurate treatment decision for SCLC patients.

Methods
Using the genomics of drug sensitivity in cancer (GDSC) database, we identified cisplatin resistance-related lncRNAs in SCLC cells. Based on the competing endogenous RNA (ceRNA) network, we identified the mRNAs correlated with the lncRNAs. Using Cox and LASSO regression analysis, a prognostic model was established. The survival prediction accuracy was evaluated by receiver operating characteristic (ROC) curve and Kaplan–Meier analysis. GSEA, GO, KEGG and CIBERSORT tools were used for functional enrichment and immune cells infiltration analysis.

Results
We first screened out 10 differentially expressed lncRNAs between cisplatin resistant and sensitive SCLC cells from GDSC database. Based on ceRNA network, 31 mRNAs were identified with a correlation with the 10 lncRNAs. Furthermore, two genes (LIMK2 and PI4K2B) were identified by Cox and LASSO regression analysis to construct a prognostic model. Kaplan–Meier analysis indicated that the high-risk group had a poor overall survival compared with the low-risk group. The predicted area under the ROC curve (AUC) was 0.853 in the training set, and the AUC was 0.671 in the validation set. In the meanwhile, the low expression of LIMK2 or the high expression of PI4K2B in SCLC tumors was also significantly associated with poor overall survival in both training and validation sets. Functional enrichment analysis showed that the low-risk group was enriched in the apoptosis pathway and high immune infiltration of T cells. Finally, an apoptosis-related gene Cathepsin D (CTSD) was identified to be up-regulated in the low-risk group, and its higher expression correlated with better overall survival in SCLC.

Conclusion
We established a prognostic model and potential biomarkers (LIMK2, PI4K2B and CTSD), which could help to improve the risk stratification of SCLC patients.
Association between triglyceride glucose index and arterial stiffness and coronary artery calcification: a systematic review and exposure-effect meta-analysis
Authors: Liu Fuwei , Ling Qin , Xie Shaofeng , Xu Yi , Liu Menglu , Hu Qingwen , Ma Jianyong , Yan Zhiwei , Gao Yan , Zhao Yujie , Zhu Wengen , Yu Peng , Luo Jun , Liu Xiao 
Published: May 2023

Abstract
Background
The triglyceride and glucose (TyG) index has been linked to various cardiovascular diseases. However, it's still unclear whether the TyG index is associated with arterial stiffness and coronary artery calcification (CAC).

Methods
We conducted a systematic review and meta-analysis of relevant studies until September 2022 in the PubMed, Cochrane Library, and Embase databases. We used a random-effects model to calculate the pooled effect estimate and the robust error meta-regression method to summarize the exposure-effect relationship.

Results
Twenty-six observational studies involving 87,307 participants were included. In the category analysis, the TyG index was associated with the risk of arterial stiffness (odds ratio [OR]: 1.83; 95% CI 1.55–2.17, I2 = 68%) and CAC (OR: 1.66; 95% CI 1.51–1.82, I2 = 0). The per 1-unit increment in the TyG index was also associated with an increased risk of arterial stiffness (OR: 1.51, 95% CI 1.35–1.69, I2 = 82%) and CAC (OR: 1.73, 95% CI 1.36–2.20, I2 = 51%). Moreover, a higher TyG index was shown to be a risk factor for the progression of CAC (OR = 1.66, 95% CI 1.21–2.27, I2 = 0, in category analysis, OR = 1.47, 95% CI 1.29–1.68, I2 = 41% in continuity analysis). There was a positive nonlinear association between the TyG index and the risk of arterial stiffness (Pnonlinearity < 0.001).

Conclusion
An elevated TyG index is associated with an increased risk of arterial stiffness and CAC. Prospective studies are needed to assess causality.

Graphical Abstract
Effects of sumac supplementation on metabolic markers in adults with metabolic syndrome: a triple-blinded randomized placebo-controlled cross-over clinical trial
Authors: Mirenayat Fateme Sadat , Hajhashemy Zahra , Siavash Mansour , Saneei Parvane 
Published: May 2023

Abstract
Background
Despite the prior evidence of the impacts of sumac on glycemic indices, lipid profile and visceral fat, there is a lack of evidence regarding the efficacy of sumac in cases with metabolic syndrome (MetS). Therefore, we aimed to assess the effect of sumac supplementation on MetS markers among adults with this syndrome.

Methods
In this triple-blinded randomized placebo-controlled cross-over clinical trial 47 adults with MetS were randomly assigned to receive 500 mg sumac or placebo (lactose) capsule, twice a day. Each phase took 6 weeks and there was a 2-week washout between phases. All clinical evaluations and laboratory tests were conducted before and after each phase.

Results
At the baseline of the study, mean (± SD) age, weight, and waist circumference of participants were respectively 58.7 (± 5.8) yr, 79.9 (± 14.3) kg, and 107.6 (± 10.8) cm. Intention to treat analysis (ITT) analyses revealed that sumac supplementation decreased systolic blood pressure by 5 mmHg (128.8 ± 21.4 at the baseline vs. 123.2 ± 17.6 after 6 weeks intervention, P = 0.001). The comparison of changes in two trial arms showed that sumac supplementation significantly reduced systolic blood pressure (sumac group -5.59 ± 10.6 vs. control group 0.76 ± 10.5, P = 0.004), but did not change anthropometric indices or diastolic blood pressure. Similar results were also found in the per-protocol analyses.

Conclusions
This cross-over trial revealed that sumac supplementation could reduce systolic blood pressure in men and women with MetS. Daily intake of 1000 mg sumac, as an adjuvant therapy, may be beneficial in management of MetS in adults.
Clinical trial assessing the safety of edoxaban with concomitant chemotherapy in patients with gynecological cancer-associated thrombosis (EGCAT study)
Authors: Oride Tadashi , Sawada Kenjiro , Shimizu Aasa , Kinose Yasuto , Takiuchi Tsuyoshi , Kodama Michiko , Hashimoto Kae , Kobayashi Eiji , Nakatani Eiji , Kimura Tadashi 
Published: May 2023

Abstract
Background
Gynecological cancer is one of the highest risk factors for cancer-associated thrombosis (CAT). Although low-molecular-weight heparin (LMWH) is recommended as an anticoagulant for treating CAT, recent studies have shown that direct oral anticoagulants (DOACs) are an acceptable alternative. Patients with cancer require a series of chemotherapies concomitantly with DOAC administration; however, the extent to which these drugs influence DOAC blood concentrations is unknown. In this study, we measured the plasma concentration of edoxaban during chemotherapy for gynecological cancers to determine its safety.

Methods
Patients histologically diagnosed with ovarian or uterine corpus cancer and CAT were recruited after primary surgery and before the initiation of postoperative adjuvant chemotherapy, including paclitaxel. Patients were administered edoxaban (30 or 60 mg) orally for CAT. The plasma concentrations of edoxaban and active factor Xa were determined and their percentage change before and after chemotherapy was calculated. Additionally, blood coagulation tests were analyzed.

Results
Sixteen patients with gynecological cancer (12 with ovarian cancer and 4 with uterine corpus cancer) were enrolled. Among these, 15 samples were collected one day after chemotherapy initiation. During chemotherapy, the trough concentration of edoxaban changed from 17.6 ± 10.6 to 20.0 ± 15.6 ng/ml, and the mean percentage change in edoxaban concentration was 14.5%. Therefore, the trough concentrations of edoxaban, which represent excretion capacity, were not significantly increased by chemotherapy with paclitaxel. The area under the plasma edoxaban concentration–time curve and the active factor Xa concentration were also unaffected.

Conclusion
Patients with CAT and ovarian or uterine corpus cancer administered edoxaban orally showed no significant increase in the trough concentration of edoxaban while undergoing chemotherapy. This suggests the safety of edoxaban use during the treatment of gynecological cancers.

Trial registration
EGCAT study; Japan Registry of Clinical Trials, jRCTs051190024.
Attracting adolescents to become doctors and nurses: differential importance of personal and environmental factors in 61 economies
Authors: Guo Luyang , Hau Kit-Tai 
Published: May 2023

Abstract
Background
Doctors and nurses play a fundamental role in maintaining global health systems and achieving universal health care coverage. However, significant shortages persist, and little is known about the popularity of these careers among young people in various economies or the relative impact of personal inputs and contextual factors.

Methods
Using data from the large-scale Programme of International Student Assessment (PISA) 2018, we showed the recent distribution of adolescents' medical (doctor) and nursing career expectations in 61 economies. With multilevel logistic and hierarchical linear regression, we examined the relative importance of economic indicators, health work conditions, and personal background factors in affecting adolescents' health career expectations.

Results
Approximately 11% of adolescents expected to be doctors in each economy, while only 2% expected to be nurses. Adolescents were attracted to health professions mainly by system-level favourable conditions (accounting for 1/3 variance), including (a) government health expenditure beyond that expected gross domestic product (GDP); (b) a safe working environment for doctors in wealthy nations; and (c) high salaries for nurses in less-developed economies. In contrast, adolescents' background (gender, social status, and academic ability) was less influential, explaining only 10% of the differences.

Conclusions
In the technological and digital era, high-ability students are equally competitive for emerging careers other than doctors and nurses. In developing countries, a high salary package and societal respect are enough to attract adolescents to nursing careers. In contrast, for developed countries, extra expenditures beyond regular GDP allocation and a safe work environment are crucial in attracting adolescents to become doctors. Salary may effectively attract international-trained doctors and nurses, but the work environment will likely emerge as an essential factor in retaining migrants in their positions.
Trial registration number: No human participants were involved in this study.
What are economic costs and when should they be used in health economic studies?
Authors: Turner Hugo C. , Sandmann Frank G. , Downey Laura E. , Orangi Stacey , Teerawattananon Yot , Vassall Anna , Jit Mark 
Published: May 2023

AbstractEconomic analyses of healthcare interventions are an important consideration in evidence-based policymaking. A key component of such analyses is the costs of interventions, for which most are familiar with using budgets and expenditures. However, economic theory states that the true value of a good/service is the value of the next best alternative forgone as a result of using the resource and therefore observed prices or charges do not necessarily reflect the true economic value of resources. To address this, economic costs are a fundamental concept within (health) economics. Crucially, they are intended to reflect the resources’ opportunity costs (the forgone opportunity to use those resources for another purpose) and they are based on the value of the resource's next-best alternative use that has been forgone. This is a broader conceptualization of a resource’s value than its financial cost and recognizes that resources can have a value that may not be fully captured by their market price and that by using a resource it makes it unavailable for productive use elsewhere. Importantly, economic costs are preferred over financial costs for any health economic analyses aimed at informing decisions regarding the optimum allocation of the limited/competing resources available for healthcare (such as health economic evaluations), and they are also important when considering the replicability and sustainability of healthcare interventions. However, despite this, economic costs and the reasons why they are used is an area that can be misunderstood by professionals without an economic background. In this paper, we outline to a broader audience the principles behind economic costs and when and why they should be used within health economic analyses. We highlight that the difference between financial and economic costs and what adjustments are needed within cost calculations will be influenced by the context of the study, the perspective, and the objective.
Bacterial extracellular vesicles repress the vascular protective factor RNase1 in human lung endothelial cells
Authors: Laakmann Katrin , Eckersberg Jorina Mona , Hapke Moritz , Wiegand Marie , Bierwagen Jeff , Beinborn Isabell , Preußer Christian , Pogge von Strandmann Elke , Heimerl Thomas , Schmeck Bernd , Jung Anna Lena 
Published: May 2023

Abstract
Background
Sepsis is one of the leading causes of death worldwide and characterized by blood stream infections associated with a dysregulated host response and endothelial cell (EC) dysfunction. Ribonuclease 1 (RNase1) acts as a protective factor of vascular homeostasis and is known to be repressed by massive and persistent inflammation, associated to the development of vascular pathologies. Bacterial extracellular vesicles (bEVs) are released upon infection and may interact with ECs to mediate EC barrier dysfunction. Here, we investigated the impact of bEVs of sepsis-related pathogens on human EC RNase1 regulation.

Methods
bEVs from sepsis-associated bacteria were isolated via ultrafiltration and size exclusion chromatography and used for stimulation of human lung microvascular ECs combined with and without signaling pathway inhibitor treatments.

Results
bEVs from Escherichia coli, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium significantly reduced RNase1 mRNA and protein expression and activated ECs, while TLR2-inducing bEVs from Streptococcus pneumoniae did not. These effects were mediated via LPS-dependent TLR4 signaling cascades as they could be blocked by Polymyxin B. Additionally, LPS-free ClearColi™ had no impact on RNase1. Further characterization of TLR4 downstream pathways involving NF-кB and p38, as well as JAK1/STAT1 signaling, revealed that RNase1 mRNA regulation is mediated via a p38-dependent mechanism.

Conclusion
Blood stream bEVs from gram-negative, sepsis-associated bacteria reduce the vascular protective factor RNase1, opening new avenues for therapeutical intervention of EC dysfunction via promotion of RNase1 integrity.