bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selectively down-regulated PD-L1 by albumin-phenformin nanoparticles mediated mitochondrial dysfunction to stimulate tumor-specific immunological response for enhanced mild-temperature photothermal efficacy
Authors: Zhou Zaigang , Jiang Ning , Chen Jiashe , Zheng Chunjuan , Guo Yuanyuan , Ye Ruirong , Qi Ruogu , Shen Jianliang 
Published: November 2021

Abstract
Background
Mild-temperature photothermal therapy (mild-PTT) has emerged as a highly promising antitumor strategy by triggering immunogenic cell death (ICD) to elicit both innate and adaptive immune responses for tumor control. However, mild-PTT still leads to the risk of tumor recurrence or metastasis because it could hardly completely eradicate tumors due to its impaired immunological efficacy owing to the enhanced PD-L1 expression in tumor cells after treatment.

Results
In this study, we described a hydrogen peroxide (H2O2) responsive manganese dioxide mineralized albumin nanocomposite loading with mitochondria function inhibitor phenformin (PM) and near-infrared photothermal dye indocyanine green (ICG) by modified two-step biomineralization method. In combination with ICG induced mild-PTT and PM mediated mitochondria dysfunction, PD-L1 expression was obviously down-regulated and the generated immunological responses was able to effectively attack the remaining tumor cells. Meanwhile, the risk of tumor metastasis was effectively inhibited by reducing the expression of tumor invasion-related signal molecules (TGF-β and vimentin) after combining treatment.

Conclusion
Such a strategy offers novel insight into the development of nanomedicine for mild-PTT as well as cancer immunotherapy, which can provide protection against tumor relapse post elimination of their initial and metastatic tumors.

Graphical Abstract
The impact of shelf tags with Nutri-Score on consumer purchases: a difference-in-difference analysis of a natural experiment in supermarkets of a major retailer in Belgium
Authors: Vandevijvere Stefanie , Berger Nicolas 
Published: November 2021

Abstract
Background
Delhaize, a major Belgian retailer, started implementing electronic shelf labels (ESL) with Nutri-Score since May 2019. Nutri-Score rates the healthfulness of packaged foods with five colours/letters from red/E (least healthy) to green/A (most healthy). This study evaluated the impact of ESL on consumer purchases, overall, and by food category.

Methods
For 43 intervention stores (implementing ESL in the period 27 May 2019–19 June 2019), a control store, from the same province and retailer-assigned cluster was matched. There were 14 unique control stores. By store, weekly non-food and food sales for 2018 and 2019 were received by Nutri-Score (A/B/C/D/E) and food category according to a retailer-assigned classification system. The primary outcomes were the proportion of food sales for Nutri-Score A,B,C,D,E. Difference-in-differences regression analysis was conducted to estimate the effect of the ESL intervention on proportion of overall food and food category sales for Nutri-Score A,B,C,D,E, using linear mixed models to account for clustering at store-level. We controlled for store characteristics (region, cluster, non-food sales) and week of the year. Analyses were weighted to re-balance discrepancy between the number of intervention and control stores. To account for multiple testing, a Bonferroni adjustment was applied.

Results
Comparing pre- and post-intervention periods, difference-in-differences for the proportion of Nutri-Score B and C product sales were more favourable in intervention than control stores (0.11 ± 0.04%, p = 0.007 and − 0.06 ± 0.03%, p = 0.026 respectively), while difference-in-differences for the proportion of Nutri-Score D product sales were less favourable in intervention than control stores (0.12 ± 0.04%, p = 0.002). For 17/58 food categories (representing 29% of total food sales) a positive impact [increase in healthier (Nutri-Score A, B) and/or decrease in less healthy (Nutri-Score D, E) food sales], and for 16/58 categories (representing 24% of total food sales) a negative impact was found. Positive impacts were found for vegetable, fruit and dairy products and confectionery. Negative impacts were found for bread and bakery products.

Conclusion
The impact of ESL on consumer purchases was mixed. Favourable difference-in-differences were found for Nutri-Score B and C products and unfavourable difference-in-differences for Nutri-Score D products. Shelf labeling on its own is unlikely to significantly influence consumer behaviours.
FUSE binding protein FUBP3 is a potent regulator in Japanese encephalitis virus infection
Authors: Xu Peng , Tong Wei , Chen Young-Mao 
Published: November 2021

Abstract
Background
The JEV genome is a positive-sense RNA with a highly structured capped 5′UTR, 3′UTR and a large open reading frame. 3′UTR is the untranslated region of flavivirus and has various important functions during viral replication, such as translation, replication and encapsidation. During viral replication, the 3′UTR interacts with viral proteins and host proteins and is required for viral RNA replication and translocation.

Methods
The expression level of FUBP3 was knocked down by siRNA and Flag-tagged FUBP3 overexpression plasmid was constructed for overexpression. BHK-21 cells were cultured and infected with JEV to investigate the functional role of FUBP3 in the viral infection cycle. Subcellular localization of FUBP3 and viral replication complexes was observed by dual immunofluorescence staining.

Results
Four host proteins were specifically associated with the 3′UTR of JEV, and FUBP3 was selected to further investigate its potential functional role in the JEV infection cycle. Knockdown of FUBP3 protein resulted in a significant decrease in JEV viral titer, whereas ectopic overexpression of FUBP3 resulted in increased JE viral infectivity. In cells stably knocked down for FUBP3 and then infected with JEV, we found almost no detectable viral NS5 protein. In contrast, when cells stably knocking-down of FUBP3 overexpressed FUBP3, we found a significant increase in viral RNA production over time compared to controls. We also demonstrated that FUBP3 re-localized in the cytoplasm after infection with JEV and co-localized with viral proteins. Exogenous overexpression of FUBP3 was also shown to be located in the JE replication complex and to assist viral replication after JEV infection.

Conclusions
The overall results suggest that FUBP3 regulates RNA replication of JEV and promotes subsequent viral translation and viral particle production.
Scientific evidence based rare disease research discovery with research funding data in knowledge graph
Authors: Zhu Qian , Nguyễn Ðắc-Trung , Sheils Timothy , Alyea Gioconda , Sid Eric , Xu Yanji , Dickens James , Mathé Ewy A. , Pariser Anne 
Published: November 2021

Abstract
Background
Limited knowledge and unclear underlying biology of many rare diseases pose significant challenges to patients, clinicians, and scientists. To address these challenges, there is an urgent need to inspire and encourage scientists to propose and pursue innovative research studies that aim to uncover the genetic and molecular causes of more rare diseases and ultimately to identify effective therapeutic solutions. A clear understanding of current research efforts, knowledge/research gaps, and funding patterns as scientific evidence is crucial to systematically accelerate the pace of research discovery in rare diseases, which is an overarching goal of this study.

Methods
To semantically represent NIH funding data for rare diseases and advance its use of effectively promoting rare disease research, we identified NIH funded projects for rare diseases by mapping GARD diseases to the project based on project titles; subsequently we presented and managed those identified projects in a knowledge graph using Neo4j software, hosted at NCATS, based on a pre-defined data model that captures semantics among the data. With this developed knowledge graph, we were able to perform several case studies to demonstrate scientific evidence generation for supporting rare disease research discovery.

Results
Of 5001 rare diseases belonging to 32 distinct disease categories, we identified 1294 diseases that are mapped to 45,647 distinct, NIH-funded projects obtained from the NIH ExPORTER by implementing semantic annotation of project titles. To capture semantic relationships presenting amongst mapped research funding data, we defined a data model comprised of seven primary classes and corresponding object and data properties. A Neo4j knowledge graph based on this predefined data model has been developed, and we performed multiple case studies over this knowledge graph to demonstrate its use in directing and promoting rare disease research.

Conclusion
We developed an integrative knowledge graph with rare disease funding data and demonstrated its use as a source from where we can effectively identify and generate scientific evidence to support rare disease research. With the success of this preliminary study, we plan to implement advanced computational approaches for analyzing more funding related data, e.g., project abstracts and PubMed article abstracts, and linking to other types of biomedical data to perform more sophisticated research gap analysis and identify opportunities for future research in rare diseases.
Analgesia in pediatric trauma patients in physician-staffed Austrian helicopter rescue: a 12-year registry analysis
Authors: Rugg Christopher , Woyke Simon , Ausserer Julia , Voelckel Wolfgang , Paal Peter , Ströhle Mathias 
Published: November 2021

AbstractBackgroundAs pediatric patients are typically rare among helicopter emergency medical systems (HEMS), children might be at risk for oligo-analgesia due to the rescuer’s lack of experience and the fear of side effects.MethodsIn this retrospective analysis, data was obtained from the ÖAMTC HEMS digital database including 14 physician staffed helicopter bases in Austria over a 12-year timeframe. Primary missions involving pediatric trauma patients (< 15 years) not mechanically ventilated on-site were included. Analgesia was assessed and compared between the age groups 0–5, 6–10 and 11–14 years.ResultsOf all flight missions, 8.2% were dedicated to children < 15 years. Analgetic drugs were administered in 31.4% of all primary missions (3874 of 12,324), wherefrom 2885 were injured and non-ventilated (0–5 yrs.: n = 443; 6–10 yrs.: n = 902; 11–14 yrs.: n = 1540). The majority of these patients (> 75%) suffered moderate to severe pain, justifying immediate analgesia. HEMS physicians typically chose a monotherapy with an opioid (n = 1277; 44.3%) or Esketamine (n = 1187; 41.1%) followed by the combination of both (n = 324; 11.2%). Opioid use increased (37.2% to 63.4%) and Esketamine use decreased (66.1% to 48.3%) in children < 6 vs. > 10 years. Esketamine was more often administered in extremity (57.3%) than in head (41.5%) or spine injuries (32.3%). An intravenous access was less often established in children < 6 years (74.3% vs. 90.8%; p < 0.001). Despite the use of potent analgesics, 396 missions (13.7%) were performed without technical monitoring. Particularly regarding patient data at handover in hospital, merely < 10% of all missions featured complete documentation. Therefore, sufficient evaluation of the efficacy of pain relief was not possible. Yet, by means of respiratory measures required during transport, severe side effects such as respiratory insufficiency, were barely noted.ConclusionsIn the physician-staffed HEMS setting, pediatric trauma patients liberally receive opioids and Esketamine for analgesia. With regard to severe respiratory insufficiency during transport, the application of these potent analgesics seems safe.
Cardiogenic shock in Taiwan from 2003 to 2017 (CSiT-15 study)
Authors: Chien Shih-Chieh , Hsu Chien-Yi , Liu Hung-Yi , Lin Chao-Feng , Hung Chung-Lieh , Huang Chun-Yao , Chien Li-Nien 
Published: November 2021

Abstract
Background
This study investigated temporal trends in the treatment and mortality of patients with cardiogenic shock (CS) in Taiwan in relation to acute myocardial infarction (AMI) accreditation implemented in 2009 and the unavailability of percutaneous ventricular assist devices.

Methods
Data of patients diagnosed as having CS between January 2003 and December 2017 were collected from Taiwan’s National Health Insurance Research Database. Each case was followed from the date of emergency department arrival or hospital admission for the first incident associated with a CS diagnosis up to a 1-year interval. Measurements included demographics, comorbidities, treatment, mortality, and medical costs. Using an interrupted time-series (ITS) design with multi-level mixed-effects logistic regression model, we assessed the impact of AMI accreditation implementation on the mortality of patients with AMI and CS overall and stratified by the hospital levels.

Results
In total, 64 049 patients with CS (mean age:70 years; 62% men) were identified. The incidence rate per 105 person-years increased from 17 in 2003 to 25 in 2010 and plateaued thereafter. Average inpatient costs increased from 159 125 points in 2003 to 240 993 points in 2017, indicating a 1.5-fold increase. The intra-aortic balloon pump application rate was approximately 22–25% after 2010 (p = 0.093). Overall, in-hospital, 30-day, and 1-year mortality declined from 60.3%, 63.0%, and 69.3% in 2003 to 47.9%, 50.8% and 59.8% in 2017, respectively. The decline in mortality was more apparent in patients with AMI-CS than in patients with non-AMI-CS. The ITS estimation revealed a 2% lower in-hospital mortality in patients with AMI-CS treated in district hospitals after the AMI accreditation had been implemented for 2 years.

Conclusions
In Taiwan, the burden of CS has consistently increased due to high patient complexity, advanced therapies, and stable incidence. Mortality declined over time, particularly in patients with AMI-CS, which may be attributable to advancements in AMI therapies and this quality-improving policy.
On new general versions of Hermite–Hadamard type integral inequalities via fractional integral operators with Mittag-Leffler kernel
Authors: Kavurmacı Önalan Havva , Akdemir Ahmet Ocak , Avcı Ardıç Merve , Baleanu Dumitru 
Published: November 2021

AbstractThe main motivation of this study is to bring together the field of inequalities with fractional integral operators, which are the focus of attention among fractional integral operators with their features and frequency of use. For this purpose, after introducing some basic concepts, a new variant of Hermite–Hadamard (HH-) inequality is obtained for s-convex functions in the second sense. Then, an integral equation, which is important for the main findings, is proved. With the help of this integral equation that includes fractional integral operators with Mittag-Leffler kernel, many HH-type integral inequalities are derived for the functions whose absolute values of the second derivatives are s-convex and s-concave. Some classical inequalities and hypothesis conditions, such as Hölder’s inequality and Young’s inequality, are taken into account in the proof of the findings.
The application of the QALY measure in the assessment of the effects of health interventions on an older population: a systematic scoping review
Authors: Kocot Ewa , Kotarba Paulina , Dubas-Jakóbczyk Katarzyna 
Published: November 2021

Abstract
Background
One of the most commonly used types of evaluation methods is cost-utility analysis (CUA), using the Quality Adjusted Life Year (QALY) indicator as a preference-based measure for assessing effects of a given programme. Such assessments are often translated into health-care provision priorities; therefore, effectively choosing the method of outcome evaluation is crucial for ensuring the best possible allocation of scarce resources. The main objective of this scoping review is to identify what kinds of problems and limitations may occur when the QALY indicator is used to assess the effects of health interventions in the older population.

Methods
To identify literature in a scoping review, the databases MEDLINE via PubMed and Scopus were searched. A manual search on relevant organizations’ and associations’ websites was also conducted (EUnetHTA, ISPOR and national governmental agencies responsible for allocation decisions). No limits concerning publication dates were set. All relevant data were extracted and analyzed, then a narrative summary was prepared.

Results
The database search identified 10,832 relevant items, finally 32 studies were included in the analysis. The main types of issues indicated in the studies were as follows: (1) lower life expectancy in the older population causes lower QALY gains; (2) an equal value of one QALY is used regardless of age; (3) poorer average health state causes lower QALY gains; (4) inadequate instruments to measure quality of life (QoL); (5) attributes of QoL used regardless of age; and (6) no beyond-health QoL aspects taken into account.

Conclusions
This review shows clearly that many problems of different types are connected with using QALY for the older population, but there is no consensus as to whether QALY discriminates against the older population or not – an opinion regarding this issue depends strongly on accepted principles, particularly the approach to equity and how one understands fairness. Health care resources should not be allocated solely on the basis of the health maximization rule because this can lead to discrimination against certain groups (e.g., older, disabled, and/or chronically ill people). To maintain the balance between efficiency and equity, the issues connected with age-based rationing should be widely discussed.
“I had to change my attitude”: narratives of most significant change explore the experience of universal home visits to pregnant women and their spouses in Bauchi State, Nigeria
Authors: Belaid Loubna , Ansari Umaira , Omer Khalid , Gidado Yagana , Baba Muhammed Chadi , Daniel Lois Ezekiel , Andersson Neil , Cockcroft Anne 
Published: November 2021

Abstract
Background
Universal home visits to pregnant women and their spouses in Bauchi State, northern Nigeria, discussed local evidence about maternal and child health risks actionable by households. The expected results chain for improved health behaviours resulting from the visits was based on the CASCADA model, which includes Conscious knowledge, Attitudes, Subjective norms, intention to Change, Agency to change, Discussion of options, and Action to change. Previous quantitative analysis confirmed the impact of the visits on maternal and child outcomes. To explore the mechanisms of the quantitative improvements, we analysed participants’ narratives of changes in their lives they attributed to the visits.

Methods
Local researchers collected stories of change from 23 women and 21 men in households who had received home visits, from eight male and eight female home visitors, and from four government officers attached to the home visits program. We used a deductive thematic analysis based on the CASCADA results chain to analyze stories from women and men in households, and an inductive thematic approach to analyze stories from home visitors and government officials.

Results
The stories from the visited women and men illustrated all steps in the CASCADA results chain. Almost all stories described increases in knowledge. Stories also described marked changes in attitudes and positive deviations from harmful subjective norms. Most stories recounted a change in behaviour attributed to the home visits, and many went on to mention a beneficial outcome of the behaviour change. Men, as well as women, described significant changes. The home visitors’ stories described increases in knowledge, increased self-confidence and status in the community, and, among women, financial empowerment.

Conclusions
The narratives of change gave insights into likely mechanisms of impact of the home visits, at least in the Bauchi setting. The compatibility of our findings with the CASCADA results chain supports the use of this model in designing and analysing similar interventions in other settings. The indication that the home visits changed male engagement has broader relevance and contributes to the ongoing debate about how to increase male involvement in reproductive health.
Compilation and analysis of international from-whom-to-whom financial stock table for Japan, Korea, the United States, and China
Authors: Hagino Satoru , Kim Jiyoung 
Published: November 2021

AbstractThis paper discusses the development of international flow of funds accounts; it compiles and analyzes such accounts with a focus on the global financial crisis. For this purpose, we compile from-whom-to-whom financial stock tables for Japan, Korea, the United States, and China and combine these tables to generate a four-country international from-whom-to-whom financial stock table. Input–output analyses reveal that nonfinancial corporations in the four countries have the largest liability power-of-dispersion and that the Japanese government’s liability power-of-dispersion is large. In contrast, the financial institution sector in Japan has the largest asset power-of-dispersion. In the future, the table could be expanded to include other major Asia–Pacific countries and linked to Euro-area from-whom-to-whom financial stock tables to provide a global from-whom-to-whom financial stock table.
Autonomic vulnerability to biased perception of social inclusion in borderline personality disorder
Authors: Gerra Maria Lidia , Ardizzi Martina , Martorana Silvia , Leoni Veronica , Riva Paolo , Preti Emanuele , Marino Barbara Francesca Marta , Ossola Paolo , Marchesi Carlo , Gallese Vittorio , De Panfilis Chiara 
Published: November 2021

Abstract
Background
Individuals with Borderline Personality Disorder (BPD) feel rejected even when socially included. The pathophysiological mechanisms of this rejection bias are still unknown. Using the Cyberball paradigm, we investigated whether patients with BPD, display altered physiological responses to social inclusion and ostracism, as assessed by changes in Respiratory Sinus Arrhythmia (RSA).

Methods
The sample comprised 30 patients with BPD, 30 with remitted Major Depressive Disorder (rMDD) and 30 Healthy Controls (HC). Self-report ratings of threats toward one’s fundamental need to belong and RSA reactivity were measured immediately after each Cyberball condition.

Results
Participants with BPD showed lower RSA at rest than HC. Only patients with BPD, reported higher threats to fundamental needs and exhibited a further decline in RSA after the Inclusion condition.

Conclusions
Individuals with BPD experience a biased appraisal of social inclusion both at the subjective and physiological level, showing higher feelings of ostracism and a breakdown of autonomic regulation to including social scenarios.