bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combinatorial Normalization of Liver-Derived Cytokine Pathways Alleviates Hepatic Tumor-Associated Cachexia in Zebrafish
Authors: Fei Fei , Sun Shaoyang , Li Qiang , Pei Zhou , Wang Lei , Zhang Ranran , Luo Feihong , Yu Min , Wang Xu 
Published: December 2020

Abstract

The role and significance of liver-derived cytokines in cancer-associated cachexia syndrome remain elusive. Here we report that combinatorial counterbalances of the leptin and Igf1 signaling pathways in hepatocellular carcinoma (HCC) models significantly relieves cachexia. Double transgenic zebrafish models of HCC that stably displayed focal lesions, anorexia, and wasting of adipose and muscle tissues were first generated. Knockout of lepr or mc4r from these zebrafish partially restored appetite and exerted moderate or no effect on tissue wasting. However, genetic replenishment of Igf1 in a lepr-mutant background effectively relieved the cachexia-like phenotype without affecting tumor growth. Similarly, administration of napabucasin, a Stat3/Socs3 inhibitor, on the zebrafish HCC model, mammalian cell lines with exogenous IGF1, and two mouse xenograft models restored insulin sensitivity and rescued the wasting of nontumor tissues. Together, these results describe the synergistic impact of leptin and Igf1 normalization in treating certain HCC-associated cachexia as a practical strategy.

Significance:
Disruption of leptin signaling with normalized Igf1 expression significantly rescues anorexia, muscle wasting, and adipose wasting in Ras- and Myc-driven zebrafish models of HCC.
Tarloxotinib Is a Hypoxia-Activated Pan-HER Kinase Inhibitor Active Against a Broad Range of HER-Family Oncogenes
Authors: Estrada-Bernal Adriana , Le Anh T. , Doak Andrea E. , Tirunagaru Vijaya G. , Silva Shevan , Bull Matthew R. , Smaill Jeff B. , Patterson Adam V. , Kim Chul , Liu Stephen V. , Doebele Robert C. 
Published: December 2020

Abstract

Purpose:
Approved therapies for EGFR exon 20, ERBB2 mutations, and NRG1 fusions are currently lacking for non–small cell lung cancer and other cancers. Tarloxotinib is a prodrug that harnesses tumor hypoxia to generate high levels of a potent, covalent pan-HER tyrosine kinase inhibitor, tarloxotinib-effector (tarloxotinib-E), within the tumor microenvironment. This tumor-selective delivery mechanism was designed to minimize the dose-limiting toxicities that are characteristic of systemic inhibition of wild-type EGFR.

Experimental Design:
Novel and existing patient-derived cell lines and xenografts harboring EGFR exon 20 insertion mutations, ERBB2 mutations and amplification, and NRG1 fusions were tested in vitro and in vivo with tarloxotinib to determine its impact on cancer cell proliferation, apoptosis, and cell signaling.

Results:
Tarloxotinib-E inhibited cell signaling and proliferation in patient-derived cancer models in vitro by directly inhibiting phosphorylation and activation of EGFR, HER2, and HER2/HER3 heterodimers. In vivo, tarloxotinib induced tumor regression or growth inhibition in multiple murine xenograft models. Pharmacokinetic analysis confirmed markedly higher levels of tarloxotinib-E in tumor tissue than plasma or skin. Finally, a patient with lung adenocarcinoma harboring an ERBB2 exon 20 p.A775_G776insYVMA mutation demonstrated a dramatic clinical response to tarloxotinib.

Conclusions:
Experimental data with tarloxotinib validate the novel mechanism of action of a hypoxia-activated prodrug in cancer models by concentrating active drug in the tumor versus normal tissue, and this activity can translate into clinical activity in patients.
Evolving Plasticity for Autonomous Learning under Changing Environmental Conditions
Authors: Yaman Anil , Iacca Giovanni , Mocanu Decebal Constantin , Coler Matt , Fletcher George , Pechenizkiy Mykola 
Published: December 2020

Abstract
A fundamental aspect of learning in biological neural networks is the plasticity property which allows them to modify their configurations during their lifetime. Hebbian learning is a biologically plausible mechanism for modeling the plasticity property in artificial neural networks (ANNs), based on the local interactions of neurons. However, the emergence of a coherent global learning behavior from local Hebbian plasticity rules is not very well understood. The goal of this work is to discover interpretable local Hebbian learning rules that can provide autonomous global learning. To achieve this, we use a discrete representation to encode the learning rules in a finite search space. These rules are then used to perform synaptic changes, based on the local interactions of the neurons. We employ genetic algorithms to optimize these rules to allow learning on two separate tasks (a foraging and a prey–predator scenario) in online lifetime learning settings. The resulting evolved rules converged into a set of well-defined interpretable types, that are thoroughly discussed. Notably, the performance of these rules, while adapting the ANNs during the learning tasks, is comparable to that of offline learning methods such as hill climbing.
In Search of Due Diligence Obligations in UN Peacekeeping Operations
Authors: White Nigel D. 
Published: December 2020

Abstract
It is argued in this article that due diligence, grounded on positive duties under international human rights law, is a standard against which to measure the performance of UN peacekeeping forces. Its adoption by the UN will improve accountability, but in a controlled and principled way. A requirement that the UN act diligently to prevent human rights violations would not impose over-onerous obligations. For responsibility to be incurred an organisation must have clearly failed to take measures that were within its power to take. It is argued that the UN not only should be bound by norms of due diligence but is in fact bound by positive obligations derived from customary international human rights law. The development of some due diligence-type measures by the UN to prevent sexual abuse by peacekeepers and to protect civilians within areas of peacekeeper deployment, and the adoption of an explicit due diligence policy to delineate its relationship with non-UN security actors, are positive signs. However, the article demonstrates that the UN needs to further internalise and develop its due diligence obligations if it is to limit human rights violations committed under its watch. Furthermore, it needs to create accountability mechanisms to ensure that it develops the rather limited measures taken thus far, including provision for victims to be able to hold the organisation to account for failure to protect them from human rights violations. Only by accepting its responsibility and liability to such victims will be the UN be driven to improve its due diligence when mandating, preparing, training, deploying and directing peacekeeping operations.
Grotius and Late Medieval Ius Commune on Rebellion and Civil War
Authors: Fedele Dante 
Published: December 2020

Abstract
This paper explores the presence of late medieval ius commune in Grotius’s thought on the use of force in internal strife and war, based on De iure belli ac pacis (1625). To this end, it examines Grotius’s use of ius commune sources, and considers some similar sources, which he does not actually cite, but which relate to his discussion. By clarifying Grotius’s selection and use of ius commune sources, the paper intends to contribute to the achievement of a double aim: firstly, to determine the place of rebellion and civil war in De iure belli ac pacis, especially in relation to (external) war; and, secondly, to assess Grotius’s approach to the two former issues, particularly with regard to the criteria by which a distinction between rebellion and civil war can be drawn, and to the effects of this distinction.
Personal Data Transfers in International Trade and EU Law: A Tale of Two ‘Necessities’
Authors: Yakovleva Svetlana 
Published: December 2020

Abstract
Cross-border flows of personal data have become essential for international trade. European Union (EU) law restricts transfers of personal data to a degree that is arguably beyond what is permitted under the EU’s World Trade Organization commitments. These restrictions may be justified under trade law’s ‘necessity test.’ The article suggests that they may not pass this test. Yet, from an EU law perspective, the right to the protection of personal data is a fundamental right. An international transfer of personal data constitutes a derogation from this right and, therefore, must be consistent with another necessity test, the ‘strict necessity’ test of the derogation clause of the EU Charter of Fundamental Rights. This article shows how a simultaneous application of the trade law and EU Charter ‘necessities’ to EU restrictions on transfers of personal data creates a catch-22 situation and sketches the ways out of this compliance deadlock.
An “Echo in the Soul”: Worship Music in Evangelical Spanish-Language Latino Churches of Oregon
Authors: Berhó Deborah L. 
Published: December 2020

Abstract
While a majority of the fast-growing U.S. Latino population is Roman Catholic, a significant and growing percentage is Protestant – some calculate that they now number 10 million in the U.S. Despite this significant growth, Latino Protestant churches remain understudied, particularly the music in worship services. Several Latino theologians criticize the music as being of foreign extraction, a form of neocolonialism in the church, not an autochthonous expression of worship. However, these claims do not align with music actually being used in these congregations. This carefully documented study of 25 Spanish language Protestant churches in Oregon reveals that, while music used in worship at one time may have been created and imposed by non-Latinos, this is no longer the case, and bi-musicality is the norm, reflecting the diaspora and agency of the Latino Protestant church.
Identity Formation of Pre-service Science Teachers: Focusing on Those Who Changed Their Major to Earth Science Education in Korea
Authors: Yu Eun-Jeong , Kim Chan-Jong 
Published: December 2020

Abstract
This study is aimed at understanding the identity formation of pre-service science teachers (PST s) who are transitioning from students to teachers and from science/engineering majors to education majors. This was done using the conceptual lens of identity within a specific socio-cultural context. The participants were three undergraduate students in their mid- to late twenties who had transferred to science education from natural science or engineering majors. Collection of data included in-depth interviews, story timelines, e-mail surveys, and participant drawings. The study revealed that the PST s’ identity formation was not one common universal process; rather, each person’s experiences were individually affected positively or negatively by their life history. Although the three PST s came from very similar social backgrounds in Korea, their identity formation was categorized into three different types: determined effort, critical exploration, and continuous confusion. This research shows that the life history model of PST s’ identity formation can be based on the individual and practical support to reduce the gap between the actual self and future self within science education.
Between Humanitarianism and Imperialism
Authors: Epping Sarah 
Published: December 2020

Abstract
Between 1910 and 1917, the Students’ Christian Association of the University of Michigan sent out six alumni to go to Basra, Iraq, to do what they perceived to be humanitarian work. This study looks at the various fundraising mediums used by the organizers of this so-called “Michigan in Arabia” venture to convince potential donors to give the necessary funds. By analyzing these sources this study shows how a campus organization that ostensibly aimed to help the inhabitants of Basra instead functioned to cultivate Americans’ interests in the potential of this Persian Gulf city as a base for furthering U.S. power in the Middle East. It is important to study this short-lived U.S. engagement in Iraq because by cultivating incipient U.S. imperialism in the region, the Michigan venture provides a historical foundation for the emergence of U.S. economic, political, and strategic interests in Iraq in the long run.
Platelet/lymphocyte ratio is a significant prognostic factor for targeted therapy in patients with EGFR-mutated non-small-cell lung cancer
Authors: Liu Kejun , Jiang Guanming , Fang Nianxin , Cai Limin , Du Wei , Jia Jun 
Published: December 2020

Objective To analyze the prognostic significance of the pretreatment platelet/lymphocyte ratio (PLR) for targeted therapy in patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). Methods We conducted a retrospective study of 96 patients with EGFR-mutated advanced NSCLC who were treated at Dongguan People’s Hospital, Southern Medical University from May 2014 to December 2017. All patients received EGFR-targeted therapy until disease progression, unacceptable toxicity, or other factors. Approximately 3 days before the initial treatment, data including a detailed clinical history, physical examination, radiographic results, pathological diagnosis, and laboratory parameters including complete blood cell counts and albumin levels were evaluated. Results Patients in the PLR ≥ 190 group had shorter progression-free survival (PFS) than those in the PLR < 190 group. Furthermore, the 1-year PFS rate was worse in the PLR ≥ 190 group than in the PLR< 190 group. Multivariate analysis indicated the possible role of PLR as a prognostic factor for patients with advanced NSCLC who received EGFR-targeted therapy. Conclusions Pretreatment PLR may be an independent prognostic factor for patients with NSCLC receiving EGFR tyrosine kinase inhibitor treatment. Further studies are needed to identify the impact of PLR on EGFR-mutated NSCLC.
Breastfeeding Experiences of Baccalaureate Nursing Students: A Qualitative Study
Authors: Langford Cheryl , Gowan Marcella , Haj Monica 
Published: December 2020

Background Students returning to school who are breastfeeding face unique challenges. There is limited literature on breastfeeding university students. Several researchers have studied breastfeeding employees in the workplace. Institutions of higher education closely mimic the employment environment. Breastfeeding college students who express their milk while at school share similar challenges to employed mothers. A baccalaureate nursing program is rigorous and little is known about the challenges facing breastfeeding student nurses returning to classes. Research aim To explore the breastfeeding experience of baccalaureate nursing students. Methods Our study was a cross-sectional descriptive qualitative design. Purposive sampling was used to enroll participants ( N = 12). In depth, semi-structured interviews were conducted. Qualitative thematic analysis was used to analyze the data both manually and using Dedoose QDA software. Results An overarching theme of pervasive conflict between the role of the breastfeeding mother and the role of the student nurse surfaced. Three interrelated organizing themes also emerged; challenging, vulnerability, and resilience. Time constraints, self-care versus role demands, and structural accommodations contributed to the challenges. Only one participant indicated a knowledge of her breastfeeding rights. All of the participants expressed gratitude for faculty and community support, regardless of conflicts. Conclusion Breastfeeding participants were both vulnerable and resilient. Faculty may improve experiences through providing specific areas of support. A breastfeeding support policy outlining student rights and faculty responsibilities is needed to educate, guide, and enforce protections. Health care providers may enhance breastfeeding students’ experiences through anticipatory guidance, education, and continued support.
Adherence to and effectiveness of lenalidomide after 1 year of treatment in a real world setting
Authors: Santoleri Fiorenzo , Lasala Ruggero , Ranucci Elena , Rocchi Marco , Pulini Stefano , Morelli Anna Maria , Spadano Antonio , Costantini Alberto 
Published: December 2020

Background In combination with dexamethasone, lenalidomide is prescribed in the oral treatment of Multiple Myeloma for patients who have received at least one previous therapy. Objective The objective of this study is to evaluate medication adherence to lenalidomide of Multiple Myeloma patients, as well as Progression Free Survival and Overall Survival one year from the beginning of the treatment. Setting The study was carried out in Pescara Hospital, in Italy. All Multiple Myeloma patients who began lenalidomide therapy between January 1, 2012 and June 30, 2016 were included in our study. Methods Adherence to treatment was calculated by using the ratio between the Received Daily Dose and the Prescribed Daily Dose. Effectiveness in real world has been evaluated as Progression Free Survival and Overall Survival one year from the beginning of the treatment. Main outcomes measure: We assessed medication adherence and effectiveness of lenalidomide in the treatment of Multiple Myeloma. Results Adherence to the overall mean treatment was 0.73 ± 0.15, relative to 81 patients evaluated in our study. 32% of patients achieved an adherence equal to or greater than 80%. Real-life effectiveness in terms of Progression Free Survival and Overall Survival showed values of ​​53.75% and 88%, respectively, one year from the beginning of treatment. Conclusion The analysis of adherence in Multiple Myeloma patients treated with lenalidomide one year from the beginning of therapy reveal a concerning lack of adherence. Moreover, the lack of correlation of the levels of adherence with patient-related variables shows that, in the case of Multiple Myeloma, adherence is not related to personal, social and environmental characteristics that may determine each patient’s correct treatment implementation, but is directly influenced by disease evolution.
Conventional central venous catheters as tunnelled mid-clavicular midline catheters: Description of novel application and outcome analysis
Authors: Thiyagarajan Sivashanmugam , Ravindran Charulatha 
Published: December 2020

Background: Long peripheral catheters are the ideal devices for intermediate venous access (1–4 weeks). However due to non-availability and cost constraints, these lines are not widely adapted in developing countries. In this clinical report we describe a technique of using conventional Central Venous Catheters as Midclavicular midlines for intermediate venous access and present the outcome analysis of such catheters in the last 2 years from our institute. Methods: A single lumen conventional central venous catheter (5 Fr, 20 cm) was introduced through the deep veins of the upper arm, 1 to 1.5 cm distal to the axillary crease. The catheter was tunnelled for a distance of 5 to 7 cm to exit from Dawson’s green zone to reduce the incidence of Midline Associated Blood Stream Infection. Patients were followed up by trained staff nurses and outcome parameters were recorded. Results: Seventy six patients were enrolled and 72 patients underwent successful cannulation and completed the outcome analysis. Administration of intravenous antibiotics and chemotherapy were the commonest indications. The device served the intended duration of therapy in 66 (92%) patients for a median number of 12 (6–20) catheter days. Device related blood stream infection was 1.24/1000 catheter days and catheter related thrombosis rate was 8.3%. Conclusion: Conventional Central Venous Catheters can be effectively used as tunnelled Midclavicular midline catheters in low resource settings. The successful outcome analysis has to be confirmed by larger studies.
Prosthetic Replacement of the Scaphoid Proximal Pole: Should It Be the Future?
Authors: Ferrero Matteo , Carità Enrico , Giacalone Francesco , Teodori Julien , Donadelli Alberto , Laterza Mara , Corain Massimo , Battiston Bruno 
Published: December 2020

Background Scaphoid proximal pole fractures with avascular necrosis represent a complex surgical problem. Many reconstruction techniques are based on osteosynthesis with a vascularized or nonvascularized bone graft. These procedures do not allow early mobilization and therefore sometimes lead to unsatisfying functional results. In some cases, it is possible to perform a scaphoid hemiarthroplasty using a pyrocarbon implant (adaptive proximal scaphoid implant [APSI]) in place of the necrotic proximal pole, allowing an early mobilization and delaying palliative treatments such as 4-corner arthrodesis or proximal row carpectomy. Methods In this study, we reviewed all patients who had undergone a scaphoid hemiarthroplasty using APSI in our institutions from 1999 to 2017; the F.U. was performed through radiographic, clinical, and subjective (Disabilities of the Arm, Shoulder, and Hand) analysis. Results The performances of scaphoid proximal pole implants are encouraging; radiographic, clinical, and subjective outcomes were good, and the functional recovery proved to be fast and reliable over time. Conclusions This study reports our experience in the use of APSI implants, which proved to be a good alternative to traditional techniques for treating avascular necrosis of the proximal pole, still allowing further surgical steps in case of clinical worsening over time (wrist osteoarthritis). These patients are usually young and present high functional demands. Our experience is promising, but we believe that further evaluation over time will be needed.
Community Integration After Traumatic Brain Injury and Related Factors: A Study in the Nepalese Context
Authors: Lama Sumana , Damkliang Jintana , Kitrungrote Luppana 
Published: December 2020

Introduction Community integration is an essential component for rehabilitation among traumatic brain injury (TBI) survivors, which yields positive outcomes in terms of social activities, community participation, and productive work. A factor that usually facilitates community integration among TBI survivors is social support, whereas physical environment and fatigue are most often found as barriers. Objectives This study aimed to (1) describe the level of community integration, fatigue, physical environment, and social support of persons after TBI, and (2) examine the relationship between community integration and these three factors. Methods This is a descriptive correlational study. One hundred and twenty TBI survivors living in the communities of Province Number Three, Nepal were enrolled using the stratified sampling technique. The data were collected using the Community Integration Questionnaire, Modified Fatigue Impact Scale, Craig Hospital Inventory of Environmental Factors, and the Multidimensional Scale of Perceived Social Support. Descriptive statistics and Pearson’s correlation were used to analyze the data. Results Community integration, fatigue, and physical environment showed a moderate level, while social support revealed a high level. Fatigue was significantly correlated with overall community integration, whereas physical environment was found to correlate with two subscales of community integration, home integration and productive activities. Conclusion To enhance the level of community integration among TBI survivors, health care providers, in particular rehabilitation nurses and community nurses, should plan and implement strategies such as follow-up appointments or continued rehabilitation at home.