bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationalized inhibition of mixed lineage kinase 3 and CD70 enhances life span and antitumor efficacy of CD8+T cells
Authors: Kumar Sandeep , Singh Sunil Kumar , Viswakarma Navin , Sondarva Gautam , Nair Rakesh Sathish , Sethupathi Periannan , Dorman Matthew , Sinha Subhash C , Hoskins Kent , Thatcher Gregory , Rana Basabi , Rana Ajay 
Published: August 2020

BackgroundThe mitogen-activated protein kinases (MAPKs) are important for T cell survival and their effector function. Mixed lineage kinase 3 (MLK3) (MAP3K11) is an upstream regulator of MAP kinases and emerging as a potential candidate for targeted cancer therapy; yet, its role in T cell survival and effector function is not known.MethodsT cell phenotypes, apoptosis and intracellular cytokine expressions were analyzed by flow cytometry. The apoptosis-associated gene expressions in CD8+CD38+T cells were measured using RT2PCR array. In vivo effect of combined blockade of MLK3 and CD70 was analyzed in 4T1 tumor model in immunocompetent mice. The serum level of tumor necrosis factor-α (TNFα) was quantified by enzyme-linked immunosorbent assay.ResultsWe report that genetic loss or pharmacological inhibition of MLK3 induces CD70-TNFα-TNFRSF1a axis-mediated apoptosis in CD8+T cells. The genetic loss of MLK3 decreases CD8+T cell population, whereas CD4+T cells are partially increased under basal condition. Moreover, the loss of MLK3 induces CD70-mediated apoptosis in CD8+T cells but not in CD4+T cells. Among the activated CD8+T cell phenotypes, CD8+CD38+T cell population shows more than five fold increase in apoptosis due to loss of MLK3, and the expression of TNFRSF1a is significantly higher in CD8+CD38+T cells. In addition, we observed that CD70 is an upstream regulator of TNFα-TNFRSF1a axis and necessary for induction of apoptosis in CD8+T cells. Importantly, blockade of CD70 attenuates apoptosis and enhances effector function of CD8+T cells from MLK3−/−mice. In immune-competent breast cancer mouse model, pharmacological inhibition of MLK3 along with CD70 increased tumor infiltration of cytotoxic CD8+T cells, leading to reduction in tumor burden largely via mitochondrial apoptosis.ConclusionTogether, these results demonstrate that MLK3 plays an important role in CD8+T cell survival and effector function and MLK3-CD70 axis could serve as a potential target in cancer.
Intra-Aortic Balloon Pump Bridging to Heart Transplantation
Authors: Huckaby Lauren V. , Seese Laura M. , Mathier Michael A. , Hickey Gavin W. , Kilic Arman 
Published: August 2020

Background:
This study evaluates the impact of the 2018 allocation policy change on outcomes of orthotopic heart transplantation (OHT) in patients bridged with intra-aortic balloon pumps (IABPs).

Methods:
Adult (≥18 years) patients undergoing OHT between 2013 and 2019 who were bridged with an IABP were stratified based on temporal relation to the policy change. Univariate analysis was used to compare baseline characteristics and postoperative outcomes. Multivariate Cox regression analysis was used to estimate risk-adjusted predictors of post-transplant mortality.

Results:

A total of 1342 (8.6%) OHT patients were bridged with an IABP during the study period. Rates of bridging with IABP to OHT increased significantly after the policy change (7.0% versus 24.9%,
P
<0.001). The mean recipient age was 54.1±12.1 years with 981 (73.1%) patients being male. Baseline characteristics were similar between the 2 groups whereas post–policy change patients spent fewer days on the waitlist (15 versus 35 days,
P
<0.001), had longer ischemic times (3.5 versus 3.0 hours,
P
<0.001), and received organs from a greater distance (301 versus 105 miles,
P
<0.001). By multivariable analysis, days on the waitlist (for every 30 days; odds ratio, 1.01 [95% CI, 1.00–1.02],
P
=0.031) and diabetes mellitus (odds ratio, 1.87 [95% CI, 1.16–3.02],
P
=0.011) emerged as significant predictors of post-transplant mortality. After the policy change, waitlisted patients requiring IABP support were more likely to survive to transplant (76.4 versus 89.8%,
P
<0.001).

Conclusions:
IABP utilization has increased over 3-fold since the 2018 policy change with improved waitlist outcomes and comparable post-OHT survival. Thus, bridging patients to OHT with IABPs appears to be an effective strategy in the current era.
Challenges Facing the Economic Partnership Agreement between the EU and West Africa
Authors: Ogbodo Juliet A. 
Published: August 2020

Abstract
Six years after negotiations, the Economic Partnership Agreement between the European Union and the West African region is still in abeyance pending signatures from Nigeria. Following the fallout from the Cotonou Agreement, the proposed EPA was designed to comply with WTO rules on preferential trade agreements while reinforcing the long-standing relationship between the two parties. This article analyses the crucial challenges facing the ratification of the Agreement and the potential landmines that may be encountered with the harmonisation of the proposed agreement in the region. It shows that although the EPA provides a progressive agenda for the economic development of West Africa, effective implementation and proactive regional integration are key to realising the full potential of the Agreement.
Combined prognostic nutritional index ratio and serum amylase level during the early postoperative period predicts pancreatic fistula following pancreaticoduodenectomy
Authors: Sakamoto Teruhisa , Yagyu Takuki , Uchinaka Ei , Morimoto Masaki , Hanaki Takehiko , Watanabe Joji , Yamamoto Manabu , Matsunaga Tomoyuki , Tokuyasu Naruo , Honjo Soichiro , Fujiwara Yoshiyuki 
Published: August 2020

Abstract
Background
The aim of this study was to investigate the usefulness of the range of change in prognostic nutritional index (PNI) during the early postoperative period as a predictor of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy.

Methods
Data were retrospectively analyzed for 192 patients who underwent pancreaticoduodenectomy. Univariate and multivariate logistic regression analyses were used to evaluate perioperative variables. PNIP3-Pre ratio represented the range of change in PNI from before surgery to postoperative day (POD) 3, PNIP1-Pre ratio represented the range of change in PNI from before surgery to POD 1, and PNIP3-P1 ratio represented the range of change in PNI from POD 1 to POD 3.

Results
The area under the curve (AUC) for PNIP3-P1 for prediction of POPF following pancreaticoduodenectomy was 0.683 (P <  0.001), which was highest among PNI ratios and higher than PNI on POD 3. The AUC for serum amylase level on POD 1 was 0.704 (P <  0.001), which was superior to the corresponding AUC on POD 3. The AUC for the combination of PNIP3-P1 ratio and serum amylase level on POD 1 for prediction of POPF was higher than the AUC of either indicator alone (0.743, P <  0.001). The combination of PNIP3-P1 ratio and serum amylase level on POD 1 was an independent predictor of POPF following pancreaticoduodenectomy (P = 0.018).

Conclusions
The combination of the range of change in PNI from POD 1 to POD 3 and serum amylase levels on POD 1 may be useful for prediction of POPF following pancreaticoduodenectomy.
Health insurance benefit package in Iran: a qualitative policy process analysis
Authors: Mohamadi Efat , Takian Amirhossein , Olyaeemanesh Alireza , Rashidian Arash , Hassanzadeh Ali , Razavi Moaven , Ghazanfari Sadegh 
Published: August 2020

Abstract
Background
Insufficient transparency in prioritization of health services, multiple health insurance organizations with various and not-aligned policies, plus limited resources to provide comprehensive health coverage are among the challenges to design appropriate Health Insurance Benefit Package (HIBP) in Iran. This study aims to analyze Policy Process of Health Insurance Benefit Package in Iran.

Method
Data were collected through semi-structured interviews with 25 experts, plus document analysis and observation, from February 2014 until October 2016. Using both deductive and inductive approaches, two independent researchers conducted data content analysis. We used MAXQDA.11 software for data management.

Results
We identified 10 main themes, plus 81 sub-themes related to development and implementation of HIBP. These included: lack of transparent criteria for inclusion of services within HIBP, inadequate use of scientific evidence to determine the HIBP, lack of evaluation systems, and weak decision-making process. We propose 11 solutions and 25 policy options to improve the situation.

Conclusion
The design and implementation of HIBP did not follow an evidence-based and logical algorithm in Iran. Rather, political and financial influences at the macro level determined the decisions. This is rooted in social, cultural, and economic norms in the country, whereby political and economic factors had the greatest impact on the implementation of HIBP. To define a cost-effective HIBP in Iran, it is pivotal to develop transparent and evidence-based guidelines about the processes and the stewardship of HIBP, which are in line with upstream policies and societal characteristics. In addition, the possible conflict of interests and its harms should be minimized in advance.
Mechanisms affecting exercise ventilatory inefficiency-airflow obstruction relationship in male patients with chronic obstructive pulmonary disease
Authors: Chuang Ming-Lung 
Published: August 2020

Abstract
Background
Exercise ventilatory inefficiency is usually defined as high ventilation ($$ \dot{\mathrm{V}}\mathrm{E} $$

V
̇

E
) versus low CO2 output ($$ \dot{\mathrm{V}}\mathrm{CO}2 $$

V
̇

CO
2
). The inefficiency may be lowered when airflow obstruction is severe because $$ \dot{\mathrm{V}}\mathrm{E} $$

V
̇

E
cannot be adequately increased in response to exercise. However, the ventilatory inefficiency-airflow obstruction relationship differs to a varying degree. This has been hypothesized to be affected by increased dead space fraction of tidal volume (VD/VT), acidity, hypoxemia, and hypercapnia.

Methods
A total of 120 male patients with chronic obstructive pulmonary disease were enrolled. Lung function and incremental exercise tests were conducted, and $$ \dot{\mathrm{V}}\mathrm{E} $$

V
̇

E
versus $$ \dot{\mathrm{V}}\mathrm{CO}2 $$

V
̇

CO
2
slope ($$ \dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{CO}2\mathrm{S} $$

V
̇

E
/

V
̇

CO
2
S
) and intercept ($$ \dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{CO}2\mathrm{I} $$

V
̇

E
/

V
̇

CO
2
I
) were obtained by linear regression. Arterial blood gas analysis was also performed in 47 of the participants during exercise tests. VD/VT and lactate level were measured.

Results
VD/VTpeak was moderately positively related to $$ \dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{CO}2\mathrm{S} $$

V
̇

E
/

V
̇

CO
2
S
(r = 0.41) and negatively related to forced expired volume in 1 sec % predicted (FEV1%) (r = − 0.27), and hence the FEV1%- $$ \dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{CO}2\mathrm{S} $$

V
̇

E
/

V
̇

CO
2
S
relationship was paradoxical. The higher the $$ \dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{CO}2\mathrm{S} $$

V
̇

E
/

V
̇

CO
2
S
, the higher the pH and PaO2, and the lower the PaCO2 and exercise capacity. $$ \dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{CO}2\mathrm{I} $$

V
̇

E
/

V
̇

CO
2
I
was marginally related to VD/VTrest. The higher the $$ \dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{CO}2\mathrm{I} $$

V
̇

E
/

V
̇

CO
2
I
, the higher the inspiratory airflow, work rate, and end-tidal PCO2peak.

Conclusion
1) Dead space ventilation perturbs the airflow- $$ \dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{CO}2\mathrm{S} $$

V
̇

E
/

V
̇

CO
2
S
relationship, 2) increasing ventilation thereby increases $$ \dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{CO}2\mathrm{S} $$

V
̇

E
/

V
̇

CO
2
S
to maintain biological homeostasis, and 3) the physiology- $$ \dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{CO}2\mathrm{S} $$

V
̇

E
/

V
̇

CO
2
S
- $$ \dot{\mathrm{V}}\mathrm{E}/\dot{\mathrm{V}}\mathrm{CO}2\mathrm{I} $$

V
̇

E
/

V
̇

CO
2
I
relationships are inconsistent in the current and previous studies.

Trial Registration
MOST 106–2314-B-040-025.
The effect of an antibiotic stewardship program on tigecycline use in a Tertiary Care Hospital, an intervention study
Authors: Moghnieh Rima , Abdallah Dania , Awad Lyn , Jadayel Marwa , Haddad Nicholas , Tamim Hani , Zaiter Aline , Awwad Diana-Caroline , Sinno Loubna , El-Hassan Salam , Lakkis Rawad , Khalil Rabab , Jisr Tamima 
Published: August 2020

Abstract
Background
A drug-oriented antibiotic stewardship intervention targeting tigecycline utilization was launched at Makassed General Hospital, Beirut, Lebanon, in 2016 as a part of a comprehensive Antibiotic Stewardship Program (ASP). In this study, we evaluated the effect of this intervention on changing tigecycline prescription behavior in different types of infections, patient outcome and mortality, along with tigecycline drug use density, when compared to an earlier period before the initiation of ASP.

Methods
This is a retrospective chart review of all adult inpatients who received tigecycline for more than 72 h between Jan-2012 and Dec-2013 [period (P) 1 before ASP] and between Oct-2016 and Dec-2018 [period (P) 2 during ASP].

Results
Tigecycline was administered to 153 patients during P1 and 116 patients during P2. The proportion of patients suffering from cancer, those requiring mechanical ventilation, and those with hemodynamic failure was significantly reduced between P1 and P2. The proportion of patients who received tigecycline for FDA-approved indications increased from 19% during P1 to 78% during P2 (P < 0.001). On the other hand, its use in off-label indications was restricted, including ventilator-associated pneumonia (26.1% in P1, 3.4% in P2, P < 0.001), hospital-acquired pneumonia (19.6% in P1, 5.2% in P2, P = 0.001), sepsis (9.2% in P1, 3% in P2, P = 0.028), and febrile neutropenia (15.7% in P1, 0.9% in P2, P < 0.001). The clinical success rate of tigecycline therapy showed an overall significant increase from 48.4% during P1 to 65.5% during P2 (P = 0.005) in the entire patient population. All-cause mortality in the tigecycline-treated patients decreased from 45.1% during P1 to 20.7% during P2 (P < 0.0001). In general, mean tigecycline consumption decreased by 55% between P1 and P2 (P < 0.0001).

Conclusion
The drug-oriented ASP intervention targeting tigecycline prescriptions improved its use and patient outcomes, where it helped curb the over-optimistic use of this drug in off-label indications where it is not a suitable treatment option.
CAS: corpus of clinical cases in French
Authors: Grabar Natalia , Dalloux Clément , Claveau Vincent 
Published: August 2020

Abstract
Background
Textual corpora are extremely important for various NLP applications as they provide information necessary for creating, setting and testing those applications and the corresponding tools. They are also crucial for designing reliable methods and reproducible results. Yet, in some areas, such as the medical area, due to confidentiality or to ethical reasons, it is complicated or even impossible to access representative textual data. We propose the CAS corpus built with clinical cases, such as they are reported in the published scientific literature in French.

Results
Currently, the corpus contains 4,900 clinical cases in French, totaling nearly 1.7M word occurrences. Some clinical cases are associated with discussions. A subset of the whole set of cases is enriched with morpho-syntactic (PoS-tagging, lemmatization) and semantic (the UMLS concepts, negation, uncertainty) annotations. The corpus is being continuously enriched with new clinical cases and annotations. The CAS corpus has been compared with similar clinical narratives. When computed on tokenized and lowercase words, the Jaccard index indicates that the similarity between clinical cases and narratives reaches up to 0.9727.

Conclusion
We assume that the CAS corpus can be effectively exploited for the development and testing of NLP tools and methods. Besides, the corpus will be used in NLP challenges and distributed to the research community.
Genetic diversity and risk factors for the transmission of antimicrobial resistance across human, animals and environmental compartments in East Africa: a review
Authors: Katale Bugwesa Z. , Misinzo Gerald , Mshana Stephen E. , Chiyangi Harriet , Campino Susana , Clark Taane G. , Good Liam , Rweyemamu Mark M. , Matee Mecky I. 
Published: August 2020

Abstract
Background
The emergence and spread of antimicrobial resistance (AMR) present a challenge to disease control in East Africa. Resistance to beta-lactams, which are by far the most used antibiotics worldwide and include the penicillins, cephalosporins, monobactams and carbapenems, is reducing options for effective control of both Gram-positive and Gram-negative bacteria. The World Health Organization, Food and Agricultural Organization and the World Organization for Animal Health have all advocated surveillance of AMR using an integrated One Health approach. Regional consortia also have strengthened collaboration to address the AMR problem through surveillance, training and research in a holistic and multisectoral approach. This review paper contains collective information on risk factors for transmission, clinical relevance and diversity of resistance genes relating to extended-spectrum beta-lactamase-producing (ESBL) and carbapenemase-producing Enterobacteriaceae, and Methicillin-resistant Staphylococcus aureus (MRSA) across the human, animal and environmental compartments in East Africa.

Main body
The review of the AMR literature (years 2001 to 2019) was performed using search engines such as PubMed, Scopus, Science Direct, Google and Web of Science. The search terms included ‘antimicrobial resistance and human-animal-environment’, ‘antimicrobial resistance, risk factors, genetic diversity, and human-animal-environment’ combined with respective countries of East Africa. In general, the risk factors identified were associated with the transmission of AMR. The marked genetic diversity due to multiple sequence types among drug-resistant bacteria and their replicon plasmid types sourced from the animal, human and environment were reported. The main ESBL, MRSA and carbapenem related genes/plasmids were the blaCTX-Ms (45.7%), SCCmec type III (27.3%) and IMP types (23.8%), respectively.

Conclusion
The high diversity of the AMR genes suggests there may be multiple sources of resistance bacteria, or the possible exchange of strains or a flow of genes amongst different strains due to transfer by mobile genetic elements. Therefore, there should be harmonized One Health guidelines for the use of antibiotics, as well as regulations governing their importation and sale. Moreover, the trend of ESBLs, MRSA and carbapenem resistant (CAR) carriage rates is dynamic and are on rise over time period, posing a public health concern in East Africa. Collaborative surveillance of AMR in partnership with regional and external institutions using an integrated One Health approach is required for expert knowledge and technology transfer to facilitate information sharing for informed decision-making.
Psychological resilience and positive coping styles among Chinese undergraduate students: a cross-sectional study
Authors: Wu Yu , Yu Wenzhou , Wu Xiuyun , Wan Huihui , Wang Ying , Lu Guohua 
Published: August 2020

Abstract
Background
Psychological resilience and coping strategies have been found to be related to various psychological and mental health problems. Evaluations of the relationship between resilience and coping style among university students are important for developing effective health promotion strategies focused on resilience intervention to benefit students’ health and well-being. The relationship between psychological resilience and coping styles has usually been examined among adults and patients. Very few studies have investigated the relationship between resilience and coping style in university students. The present study aimed to investigate the associations between psychological resilience, students’ characteristics (gender, major and grade) and coping styles among undergraduate students.

Methods
A cross-sectional survey was conducted among undergraduate students in Shandong Province, China. Undergraduate students were randomly selected from 6 universities in 3 cities of the province using a stratified random sampling method. The questionnaire included questions on the participants’ demographic information, including gender, grade and major, measures of psychological resilience and coping style. Coping style was measured by the Simplified Coping Style Questionnaire (SCSQ). The Asian Resilience Scale (ARS) was applied to evaluate undergraduates’ psychological resilience. Multivariable regression analysis was used to examine the relationships between resilience, students’ characteristics and positive coping styles.

Results
A sample of 1743 undergraduates was analysed. The mean psychological resilience score was 70.41. The mean score for positive coping style was 24.72. Multiple regression analysis showed that three factors of psychological resilience, mood control, self-plasticity and coping flexibility, were all significant factors for positive coping styles (regression coefficient = 0.34, 0.35, 0.14, p < 0.01 for the three factors, respectively). Medical students and females had higher scores for positive coping styles than non-medical students and males (p < 0.01).

Conclusions
The research revealed that females and medical students are more likely than males and non-medical students to adopt positive coping styles. Higher psychological resilience is associated with a better positive coping style. The findings suggest that psychological education and health promotion programmes that target strengthening psychological resilience among undergraduate students may help foster positive coping styles to benefit their mental health and psychological well-being.