bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advance care planning for patients with cancer and family caregivers in Indonesia: a qualitative study
Authors: Martina Diah , Kustanti Christina Yeni , Dewantari Rahajeng , Sutandyo Noorwati , Putranto Rudi , Shatri Hamzah , Effendy Christantie , van der Heide Agnes , van der Rijt Carin C. D. , Rietjens Judith A. C. 
Published: November 2022

Abstract
Background
Individuals’ willingness to engage in advance care planning is influenced by factors such as culture and religious beliefs. While most studies on advance care planning in Asia have been performed in high-income countries, Indonesia is a lower-middle-income country, with a majority of strongly collectivist and religiously devout inhabitants. We studied the perspectives of Indonesian patients with cancer and family caregivers regarding advance care planning by first exploring their experiences with medical information-disclosure, decision-making, and advance care planning and how these experiences influence their perspectives on advance care planning.

Methods
We conducted semi-structured interviews among 16 patients with cancer and 15 family caregivers in a national cancer center in Jakarta and a tertiary academic general hospital in Yogyakarta. We performed an inductive thematic analysis using open, axial, and selective coding. The rigor of the study was enhanced by reflective journaling, dual coding, and investigator triangulation.

Results
Twenty-six of 31 participants were younger than 60 years old, 20 were Muslim and Javanese, and 17 were college or university graduates. Four major themes emerged as important in advance care planning: (1) participants’ perceptions on the importance or harmfulness of cancer-related information, (2) the importance of communicating bad news sensitively (through empathetic, implicit, and mediated communication), (3) participants’ motives for participating in medical decision-making (decision-making seen as patients’ right or responsibility, or patients’ state of dependency on others), and (4) the complexities of future planning (e.g., due to its irrelevance to participants’ religious beliefs and/or their difficulties in seeing the relevance of future planning).

Conclusions
Culturally sensitive approaches to advance care planning in Indonesia should address the importance of facilitating open communication between patients and their families, and the various perspectives on information provision, bad news communication, and decision-making. Advance care planning should focus on the exploration of patients’ values, rather than drafting treatment plans in advance.
Framing access to essential medicines in the context of Universal Health Coverage: a critical analysis of health sector strategic plans from eight countries in the WHO African region
Authors: Mhazo Alison T. , Maponga Charles C. 
Published: November 2022

Abstract
Background
Framing affects how issues are understood and portrayed. This profoundly shapes the construction of social problems and how policy options are considered. While access to essential medicines (ATM) in the World Health Organization (WHO) African Region is often framed as a societal problem, there is dominance of medical and technically oriented approaches to analyze and remedy the situation. Hence, the systematic application of social science approaches, such as framing theory, remains under-explored. Through a framing analysis of National Strategic Plans (NSPs) from eight countries, this study explores the applicability and potential usefulness of framing theory to analyze essential medicines policies.

Methods
We inductively coded the relevant NSP textual fragments using the qualitative content analysis software ATLAS.ti.22. Benford and Snow’s conceptualization of framing was used to organize the coded data into three frames: diagnostic (problems), prognostic (solutions) and motivational (values and ideological).

Results
The following five diagnostic frames were dominant or in-frame: medicine unavailability, ineffective regulation, weak supply chain management, proliferation of counterfeit (substandard or falsified) medicines and use of poor quality medicines. Diagnostic frames related to financing, affordability, efficiency and corruption were given limited coverage or out of frame. Prognostic frames corresponded with how these problems were framed. Whilst Universal Health Coverage (UHC) and its guiding principles was the dominant motivational frame, we identified some frame discordance between the global discourse and national level policies.

Conclusions
Social science approaches such as framing analysis are applicable and useful to systematically analyze essential medicine aspects. By applying framing theory, we revealed that ATM aspects in the eight countries we analyzed are more often characterized in relation to availability at the expense of affordability which undermines UHC. We conclude that whilst UHC is a strong motivational frame to guide ATM aspects, it is insufficient to inform a comprehensive approach to address the problems related to ATM at country level. To effectively advance ATM, concerned actors need to realize such limitation and endeavor to gain a deeper understanding of how problems are framed and agendas are set at country level, the processes through which ideas and knowledge become policies, including the political demands, incentives and trade-offs facing decision-makers in selecting policy priorities.
Plasma metabolomic profiling of dietary patterns associated with glucose metabolism status: The Maastricht Study
Authors: Yu Evan Yi-Wen , Ren Zhewen , Mehrkanoon Siamak , Stehouwer Coen D. A. , van Greevenbroek Marleen M. J. , Eussen Simone J. P. M. , Zeegers Maurice P. , Wesselius Anke 
Published: November 2022

Abstract
Background
Glucose metabolism has been reported to be affected by dietary patterns, while the underlying mechanisms involved remain unclear. This study aimed to investigate the potential mediation role of circulating metabolites in relation to dietary patterns for prediabetes and type 2 diabetes.

Methods
Data was derived from The Maastricht Study that comprised of 3441 participants (mean age of 60 years) with 28% type 2 diabetes patients by design. Dietary patterns were assessed using a validated food frequency questionnaire (FFQ), and the glucose metabolism status (GMS) was defined according to WHO guidelines. Both cross-sectional and prospective analyses were performed for the circulating metabolome to investigate their associations and mediations with responses to dietary patterns and GMS.

Results
Among 226 eligible metabolite measures obtained from targeted metabolomics, 14 were identified to be associated and mediated with three dietary patterns (i.e. Mediterranean Diet (MED), Dietary Approaches to Stop Hypertension Diet (DASH), and Dutch Healthy Diet (DHD)) and overall GMS. Of these, the mediation effects of 5 metabolite measures were consistent for all three dietary patterns and GMS. Based on a 7-year follow-up, a decreased risk for apolipoprotein A1 (APOA1) and docosahexaenoic acid (DHA) (RR 0.60, 95% CI 0.55, 0.65; RR 0.89, 95% CI 0.83, 0.97, respectively) but an increased risk for ratio of ω-6 to ω-3 fatty acids (RR 1.29, 95% CI 1.05, 1.43) of type 2 diabetes were observed from prediabetes, while APOA1 showed a decreased risk of type 2 diabetes from normal glucose metabolism (NGM; RR 0.82, 95% CI 0.75, 0.89).

Conclusions
In summary, this study suggests that adherence to a healthy dietary pattern (i.e. MED, DASH, or DHD) could affect the GMS through circulating metabolites, which provides novel insights into understanding the biological mechanisms of diet on glucose metabolism and leads to facilitating prevention strategy for type 2 diabetes.
TSH levels within the normal range and risk of cardiovascular and all-cause mortality among individuals with diabetes
Authors: Zhu Ping , Lao Guojuan , Chen Chuping , Luo Lihui , Gu Jing , Ran Jianmin 
Published: November 2022

Abstract
Background
Evidence regarding thyroid-stimulating hormone (TSH) levels within the normal range and mortality in adults with diabetes is scarce. This study aimed to identify the association between TSH levels and cardiovascular disease (CVD) and all-cause mortality among euthyroid patients with diabetes.

Methods
This prospective cohort study included 1830 adults with diabetes from the Third National Health and Nutrition Examination Survey III. Mortality outcomes were ascertained by linkage to National Death Index records through December 31, 2019. Participants were categorized by tertiles of TSH levels (low-normal, 0.39–1.30 mIU/L; medium-normal, 1.30–2.09 mIU/L; high-normal, 2.09–4.60 mIU/L). Multivariable Cox proportional hazards models were used to explore the association between TSH levels within the normal range and overall and CVD mortality. Furthermore, restricted cubic spline analyses were used to determine the nonlinear relationship between TSH levels and mortality.

Results
During a median follow-up of 17.1 years, 1324 all-cause deaths occurred, including 525 deaths from CVD. After multivariate adjustment, a U-shaped relationship was observed between TSH levels in euthyroid status and all-cause or CVD mortality among patients with diabetes (both P < 0.05 for nonlinearity). Compared with participants with medium-normal TSH levels, those with high-normal TSH levels had a significantly higher risk of all-cause (hazard ratio, 1.31; 95% confidence interval, 1.07–1.61) and CVD (1.52; 1.08–2.12) mortality. Similarly, low-normal TSH levels also increased all-cause (1.39; 1.12–1.73) and CVD (1.69; 1.17–2.44) mortality risk. In stratum-specific analyses, we found that high-normal TSH levels were associated with higher mortality risk in younger (< 60 years) patients with diabetes but not in older (≥ 60 years) participants.

Conclusion
Low- and high-normal serum TSH levels were associated with increased all-cause and CVD mortality in euthyroid adults with diabetes. Further studies are needed to confirm the present observation in a wider population.
Is the cholesterol-perfluoroalkyl substance association confounded by dietary fiber intake?: a Bayesian analysis of NHANES data with adjustment for measurement error in fiber intake
Authors: Linakis Matthew W , Gustafson Paul , Allen Bruce C , Bachand Annette M , Van Landingham Cynthia , Keast Debra R , Longnecker Matthew P 
Published: November 2022

Abstract
Background
Serum concentrations of total cholesterol and related lipid measures have been associated with serum concentrations of per- and polyfluoroalkyl substances (PFAS) in humans, even among those with only background-level exposure to PFAS. Fiber is known to decrease serum cholesterol and a recent report based on National Health and Nutrition Examination Survey (NHANES) showed that PFAS and fiber are inversely associated. We hypothesized that confounding by dietary fiber may account for some of the association between cholesterol and PFAS.

Methods
We implemented a Bayesian correction for measurement error in estimated intake of dietary fiber to evaluate whether fiber confounds the cholesterol-PFAS association. The NHANES measure of diet, two 24-h recalls, allowed calculation of an estimate of the “true” long-term fiber intake for each subject. We fit models to the NHANES data on serum cholesterol and serum concentration of perfluorooctanoic acid (PFOA) and two other PFAS for 7,242 participants in NHANES.

Results
The Bayesian model, after adjustment for soluble fiber intake, suggested a decrease in the size of the coefficient for PFOA by 6.4% compared with the fiber-unadjusted model.

Conclusions
The results indicated that the association of serum cholesterol with PFAS was not substantially confounded by fiber intake.
Lipoprotein(a) predicts recurrent cardiovascular events in patients with prior cardiovascular events post-PCI: five-year findings from a large single center cohort study
Authors: Xu Na , Yao Yi , Jiang Lin , Xu Jingjing , Wang Huanhuan , Song Ying , Yang Yuejin , Xu Bo , Gao Runlin , Yuan Jinqing 
Published: November 2022

Abstract
Background
It is well established that lipoprotein(a)[Lp(a)] play a vital role in atherosclerosis. Whether Lp(a) can predict recurrence of cardiovascular events (CVEs) in prior CVEs patients is still unclear. We aim to investigate its association with subsequent long-term adverse events in this high-risk population.

Methods
A total of 4,469 patients with prior CVEs history after PCI were consecutively enrolled and categorized according Lp(a) values of < 10 (low), 10 to 30 (medium), and ≥ 30 mg/dL (high). The primary endpoint was MACCE, a composite of all-cause death, myocardial infarction, stroke and unplanned revascularization.

Results
During an average of 5.0 years of follow-up, 1,078 (24.1%) and 206 (4.6%) patients experienced MACCE and all-cause death with 134 (3.0%) of whom from cardiac death. The incidence of MACCE, all-cause death and cardiac death were significantly higher in the high Lp(a) group (p < 0.05). After adjustment of confounding factors, high Lp(a) level remained an independent risk factor for MACCE (adjusted HR 1.240, 95%CI 1.065–1.443, p = 0.006), all-cause death (adjusted HR 1.445, 95%CI 1.023–2.042, p = 0.037) and cardiac death (adjusted HR 1.724, 95%CI 1.108–2.681, p = 0.016). This correlation remained significant when treated as a natural logarithm-transformed continuous variable. This finding is relatively consistent across subgroups and confirmed again in two sensitivity analyses.

Conclusions
Our present study confirmed that Lp(a) was an independent predictor for recurrent CVEs in patients with established CVEs, illustrating that Lp(a) level might be a valuable biomarker for risk stratification and prognostic assessment in this high-risk population.
Preoperative coagulation biomarkers associate with survival and pulmonary embolism after surgical treatment of non-spinal skeletal metastases
Authors: Matilainen Sanna , Kask Gilber , Nieminen Jyrki , Lassila Riitta , Laitinen Minna 
Published: November 2022

Abstract
Background
Thrombotic complications are synergistic and associated with orthopedic procedures, trauma, and malignancy. Because cancer enhances coagulation activity and vice versa, we assessed preoperative biomarkers for survival and complications after treatment of pathologic fractures in non-spinal skeletal metastases.

Patients/methods
Our study population comprised 113 actual or impending pathologic fractures in 100 patients admitted to two referral centers. Laboratory variables were collected retrospectively from patient records and analyzed related to incidence of pulmonary embolism (PE) and mortality (Kaplan-Meier and Cox regression analyses and biomarker quartiles).

Results
Preoperative coagulation variables were high without exceptions. PE occurred in 12 patients at 36 post-operative days at incidence of 11% in the lower and 13% in the upper extremity fractures. Patients with fibrinogen exceeding 5 g/l (log-rank 0.022) developed PE earlier (5 to 15 days postoperatively) than others. Also, mean patient survival with normal fibrinogen range (2–4 g/l) was 34 months, whereas it halved upon elevated fibrinogen (log-rank p = 0.009). Survival in patients with FVIII levels under 326 IU/dl (Q3) was 22 months, but only 7 months if FVIII exceeded 326 IU/dl (log-rank p = 0.002). Combined elevated fibrinogen and FVIII predicted survival: for patients with levels below threshold limits was 22 months versus only 7 months when both variables exceeded the ranges (log-rank p < 0.001). Multivariate analysis to control confounders supported an independent role of fibrinogen and FVIII for survival.

Conclusions
Our study has established fibrinogen and FVIII as potential preoperative contributors of survival and complications after treatment of metastatic fractures. These results highlight the need for novel anticoagulation and thromboprophylaxis strategies among these patients.
Antiviral role of IFITM3 in prototype foamy virus infection
Authors: Wang Zhaohuan , Tuo Xiaopeng , Zhang Junshi , Chai Keli , Tan Juan , Qiao Wentao 
Published: November 2022

Abstract
Background
Foamy viruses (FVs) are retroviruses with unique replication strategies that cause lifelong latent infections in their hosts. FVs can also produce foam-like cytopathic effects in vitro. However, the effect of host cytokines on FV replication requires further investigation. Although interferon induced transmembrane (IFITMs) proteins have become the focus of antiviral immune response research due to their broad-spectrum antiviral ability, it remains unclear whether IFITMs can affect FV replication.

Method
In this study, the PFV virus titer was characterized by measuring luciferase activity after co-incubation of PFVL cell lines with the cell culture supernatants (cell-free PFV) or the cells transfected with pcPFV plasmid/infected with PFV (cell-associated PFV). The foam-like cytopathic effects of PFV infected cells was observed to reflect the virus replication. The total RNA of PFV infected cells was extracted, and the viral genome was quantified by Quantitative reverse transcription PCR to detect the PFV entry into target cells.

Results
In the present study, we demonstrated that IFITM1-3 overexpression inhibited prototype foamy virus (PFV) replication. In addition, an IFITM3 knockdown by small interfering RNA increased PFV replication. We further demonstrated that IFITM3 inhibited PFV entry into host cells. Moreover, IFITM3 also reduced the number of PFV envelope proteins, which was related to IFITM3 promoted envelope degradation through the lysosomal pathway.

Conclusions
Taken together, these results demonstrate that IFITM3 inhibits PFV replication by inhibiting PFV entry into target cells and reducing the number of PFV envelope.
Forebrain-specific conditional calcineurin deficiency induces dentate gyrus immaturity and hyper-dopaminergic signaling in mice
Authors: Hagihara Hideo , Shoji Hirotaka , Kuroiwa Mahomi , Graef Isabella A. , Crabtree Gerald R. , Nishi Akinori , Miyakawa Tsuyoshi 
Published: November 2022

AbstractCalcineurin (Cn), a phosphatase important for synaptic plasticity and neuronal development, has been implicated in the etiology and pathophysiology of neuropsychiatric disorders, including schizophrenia, intellectual disability, autism spectrum disorders, epilepsy, and Alzheimer’s disease. Forebrain-specific conditional Cn knockout mice have been known to exhibit multiple behavioral phenotypes related to these disorders. In this study, we investigated whether Cn mutant mice show pseudo-immaturity of the dentate gyrus (iDG) in the hippocampus, which we have proposed as an endophenotype shared by these disorders. Expression of calbindin and GluA1, typical markers for mature DG granule cells (GCs), was decreased and that of doublecortin, calretinin, phospho-CREB, and dopamine D1 receptor (Drd1), markers for immature GC, was increased in Cn mutants. Phosphorylation of cAMP-dependent protein kinase (PKA) substrates (GluA1, ERK2, DARPP-32, PDE4) was increased and showed higher sensitivity to SKF81297, a Drd1-like agonist, in Cn mutants than in controls. While cAMP/PKA signaling is increased in the iDG of Cn mutants, chronic treatment with rolipram, a selective PDE4 inhibitor that increases intracellular cAMP, ameliorated the iDG phenotype significantly and nesting behavior deficits with nominal significance. Chronic rolipram administration also decreased the phosphorylation of CREB, but not the other four PKA substrates examined, in Cn mutants. These results suggest that Cn deficiency induces pseudo-immaturity of GCs and that cAMP signaling increases to compensate for this maturation abnormality. This study further supports the idea that iDG is an endophenotype shared by certain neuropsychiatric disorders.
Early postnatal alterations in follicular stress response and survival in a mouse model of Classic Galactosemia
Authors: Hagen-Lillevik Synneva , Johnson Joshua , Lai Kent 
Published: November 2022

AbstractPrimary ovarian insufficiency is characterized by accelerated loss of primordial follicles, which results in ovarian failure and concomitant menopause before age 40. About 1–3% of females in the general population are diagnosed with POI; however, greater than 80% of females with the inherited disease Classic Galactosemia will develop POI. Classic Galactosemia is caused by mutations in the GALT gene encoding the enzyme galactose-1 phosphate uridylyltransferase. While dietary restriction of galactose is lifesaving in the neonatal period, the development of complications including primary ovarian insufficiency is not mitigated. Additionally, the pattern(s) of follicle loss have not been completely characterized. The chronic accumulation of aberrant metabolites such as galactose-1-phosphate and galactitol are suspected culprits in the development of the sequelae, yet the mechanisms remain elusive.Our group uses a GalT gene-trapped mouse model to study the pathophysiology of primary ovarian insufficiency in Classic Galactosemia. We recently showed that differences in the Integrated Stress Response pathway occur in mutant ovaries that likely contribute to their primary ovarian insufficiency phenotype. Using immunofluorescent staining of histological sections of ovaries at progressive ages, we saw evidence of altered Integrated Stress Response activity in granulosa cells and primordial oocytes consistent with accelerated primordial follicle growth activation, aberrant DNA damage and/or repair, and increased cellular stress/death. Overall, our findings indicate that abnormal Integrated Stress Response in the Classic Galactosemia model ovary results in accelerated primordial follicle growth activation, sometimes referred to as “burnout.” These aberrant early events help further clarify when/how the primary ovarian insufficiency phenotype arises under galactosemic conditions.