bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type-I Interferon Signaling Is Essential for Robust Metronomic Chemo-Immunogenic Tumor Regression in Murine Breast Cancer
Authors: Vergato Cameron , Doshi Kshama A. , Roblyer Darren , Waxman David J. 
Published: April 2022

Many patients with breast cancer have a poor prognosis with limited therapeutic options. Here, we investigated the potential of chemo-immunogenic therapy as an avenue of treatment. We utilized two syngeneic mouse mammary tumor models, 4T1 and E0771, to examine the chemo-immunogenic potential of cyclophosphamide and the mechanistic contributions of cyclophosphamide-activated type-I IFN signaling to therapeutic activity. Chemically activated cyclophosphamide induced robust IFNα/β receptor-1–dependent signaling linked to hundreds of IFN-stimulated gene responses in both cell lines. Furthermore, in 4T1 tumors, cyclophosphamide given on a medium-dose, 6-day intermittent metronomic schedule induced strong IFN signaling but comparatively weak immune cell infiltration associated with long-term tumor growth stasis. Induction of IFN signaling was somewhat weaker in E0771 tumors but was followed by widespread downstream gene responses, robust immune cell infiltration, and extensive, prolonged tumor regression. The immune dependence of these effective antitumor responses was established by CD8 T-cell immunodepletion, which blocked cyclophosphamide-induced E0771 tumor regression and led to tumor stasis followed by regrowth. Strikingly, IFNα/β receptor-1 antibody blockade was even more effective in preventing E0771 immune cell infiltration and blocked the major tumor regression induced by cyclophosphamide treatment. Type-I IFN signaling is thus essential for the robust chemo-immunogenic response of these tumors to cyclophosphamide administered on a metronomic schedule.Significance:Many patients with breast cancer have few therapeutic options. We show that cyclophosphamide treatment induces extensive tumor regression in a syngeneic mouse model of breast cancer via a chemo-immunogenic mechanism linked to type-I IFN production. Our findings establish that IFN signaling is essential for the robust antitumor actions of cyclophosphamide and suggest that treatment resistance may stem from silencing the IFN pathway. This suggests a new avenue for improving breast cancer treatment efficacy.
Regulating Heritable Human Genome Editing: Drawing the Line between Legitimate and Controversial Use
Authors: Conditi Noemi 
Published: April 2022

Abstract
In general, to modify the human germline is prohibited. However, regulating the use of HHGE might be a more efficient method than the actual ban. Indeed, when genome editing is safe for introduction in clinical practices, it is frequently proposed that the prohibition is lifted solely for therapeutic purposes, i.e., to eliminate serious genetic diseases. Definitions of the concepts of health and disease are controversial and may only be reached by adopting a value-laden approach, which may rise concerns about legal certainty and have possible discriminatory effects. Nor the threshold of the seriousness of the disease might be used to solve these issues. A different model might then be adopted for the assessment of the permissibility of HHGE, i.e., the PGD model. However, such model should not be implemented as the only criterion, but should rather be a “minimum threshold”: HHGE should be allowed whenever used to correct a genetic defect for which PGD is possible.
Exemplary Lovers: Humanity and Hierarchy in Muslim Philanthropy
Authors: Mostowlansky Till 
Published: April 2022

Abstract
Islamic charity is an increasingly well-charted field of study that encompasses Muslim institutions and practices of “doing good” across time and space. What is less well charted, though, is the study of how these institutions and practices become part of a broader sphere of civic engagement through contact with Muslim and non-Muslim actors, concepts and exemplary figures. This article analyses such contact, focusing on Muslim philanthropists who lead projects and trusts across a range of social and geographical spaces, and exploring the humanitarian examples they draw on and the hierarchies they reproduce and create through their engagement. With an emphasis on exchanges between Muslim philanthropists in England, Iran and Pakistan, the article follows the spiritual connections, pilgrimage economy and moral sentiments that inform the ways these philanthropists carve out spaces for themselves.
The Cost of Frailty in Complex Gastrointestinal Surgery
Authors: Vidri Roberto J. , Mohamed Abdimajid , Mack Joseph D. , MacGillivray Dougald , Fitzgerald Timothy L. 
Published: April 2022

Background Frailty is a syndrome characterized by decreased physiologic reserve related with aging; it has been associated with increased costs of health care. Factors driving its economic impact remain poorly understood. We examine the association between frailty, complications, and costs in complex gastrointestinal surgery. Methods Retrospective review of a prospective database encompassing elective complex gastrointestinal operations from 2017 to 2018 at a tertiary care hospital. Patients were categorized into non-frail (NF): MFI 0, pre-frail (PF): MFI 1-2, and frail (FR): MFI >2 based on the 5-Factor Modified Frailty Index. Linear regression models were applied. Results 612 patients were included; 268 (44%) were NF, 325 (53%) were PF, and 19 (3%) were FR. The FR group had a longer length of stay (7.26 days) compared to NF (5.05 days) or PF (5.67 days) ( p = 0.031). The average total cost of care for all patients was $19,413.06 (CI 18,297.13-20,528.98). The cost for NF was $17,648.54 (CI 15,969.18-19,327.9), PF $20,435.70 (CI 18,911.01-21,960.4, p = .016), and FR patients was $26,809.36 (CI 20,511.9-33,106.81). A complication was observed in 91 patients (14.9%); of these, 76 (12.4%) were serious complications, as defined by NSQIP. There was no difference in incidence of complications (NF 14.93%, PF 14.46%, FR 21.05%, p = .734). On average, a complication added $12,656.67 regardless of frailty category. Discussion Frail patients are more costly and have a longer length of stay than their more robust counterparts. Complications were the major driver of costs after complex gastrointestinal surgery regardless of frailty status.
Revisiting the Gravity Model of Migration
Authors: Khan Mohammad Azeem , Fatima Zeenat , Fatima Sumbul 
Published: April 2022

The recent global migration pattern indicates the importance of the movement of people from developing countries to developed countries in search of better economic opportunities. The G20 report of ‘International Migration and Displacement Trends’ mentions India at the top of the list of highly educated emigrants in G20 countries. The current study addresses the endogeneity problem in the migration determinants and attempts to highlight the major regional and economic determinants of migration flow from India to major OECD countries using the Gravity model of migration. We apply the Prais–Winsten regression method to address the cross-sectional correlation, while we apply instrumental variable regression and Hausman–Taylor regression estimation techniques to deal with the endogeneity issue. The findings reveal that the population of India, distance, common official language and per capita income differential are the major determinants of migration from India. In the backdrop of our findings, in terms of per capita income differential, there is a need for an upward revision in the pay scale of the white-collar workers in the organised sector. JEL Codes: C23, F22, J11, J60
Strategic alignment of open government initiatives in Andalusia
Authors: Alcaide Muñoz Cristina , Alcaide Muñoz Laura , Rodríguez Bolívar Manuel Pedro 
Published: April 2022

The emergence of information and communication technologies (ICTs) has put emphasis on the open government approach (OG), provoking a cultural change in both the citizenry (demanding new ways of collaborating with public administration and more openness in government), and in the public administrations (adapting their structures and processes to support civic participation). This article analyzes both the strategies followed by local governments in implementing OG initiatives and the level of alignment of the objectives included in the municipal OG strategies with those settled by the regional government to which they belong. Empirical research on the OG objectives included in the strategic planning of large-size Andalusian municipalities has been performed. Findings reveal that most local governments are implementing a push strategy based only on more openness in government (mainly owing to normative requirements). Additionally, the objectives included in both the economic and governance dimensions are those included in the OG initiatives in municipalities, although each one has a particular way of adopting digital and OG strategies consistent with their municipal priorities and circumstances. Points for practitioners This study brings a novel insight to public managers and politicians concerning OG initiative adoption. It highlights both the limitations of current OG initiatives developed by public administration and the importance of citizens’ involvement in them in order to acquire trust in government. The current economic situation favors and increases mistrust in the citizen, who feels great disappointment in governments and political leaders. This could be minimized with the creation of spaces for municipal collaboration, where public managers and politicians may capture the voice of citizens directly and the strategic alignment in the OG strategies for efficiently reaching economic and social outcomes for the citizenry. Also, OG implementation experiences should be shared, so that more reticent local governments could be made aware of the potential.
A Multidisciplinary Quality of Care Path For Couple Infertility: Development of An Integrated Approach Founded on A Multidisciplinary, Personalistic, and Ecological Model For Couple Fertility
Authors: Grande Giuseppe , Colesso Walter , Gava Stefano , De Conto Umberto , Cusinato Mario 
Published: April 2022

The Path of Fertile Family (FFP) is a service for couples experiencing infertility, aimed to obtain natural conception, as an alternative to assisted reproductive techniques, developed in 2018 and provided by the Counseling Centre of Centro della Famiglia Foundation, an institute of culture and pastoral care of the Diocese of Treviso, in cooperation with the local socio-health unit. FFP offers to infertile couples a specific multidisciplinary path of care, including the involvement of specific gynecological, andrological, endocrinological, and psycho-relational competences, together with fertility awareness. It represents an “experiential laboratory” for the multidisciplinary diagnosis and treatment of infertility, for understanding relational processes, for the development of operational strategies and above all for the verification of the goodness of a lifestyle that is able to harmonize the couple’s project and the family’s project, couple satisfaction and parental openness. The setting of the service draws inspiration and reference from three paradigms from which significant ethical choices derive: the ecological perspective of fertility, the relational intimacy of the couple and a multidisciplinary approach. From the three founding paradigms, FFP model has been developed and progressively implemented in order to define a specific FFP Quality of Care Path (QCP) for couple infertility. Although further studies are needed to better clarify the role of each studied variable in a complex monitoring system, we identified for the first time a QCP Path based on 7 variables we present here two illustrative cases: the first one in which a natural conception has been obtained and the second one, in which the focus has been moved from natural conception to the reconstruction of relational competence. Further studies will demonstrate, on large scale, the efficacy of our protocol and of the analyzed variables. Summary: This paper provides an overview of the conceptual and methodological process of implementing the monitoring of the path of infertile couples towards natural conception in harmony with their relational life project. A multi-professional team accompanies couples in overcoming the obstacles to fertility and in the progressive awareness that parenting is not only biological. The result is a range of goals to strive for. The reference paradigms of the service justify the ethical choices of the couple and the team. The operating protocol supports the couple commitment and guides professionals in their effective action if competent and concerted. The variables identified are the monitoring tool that gradually indicates the degree of the path progress.
Management for Warthin Tumor of the Parotid Gland: Surgery or Observation. A 21-Year Retrospective Study of 387 Cases
Authors: Nishimura Hiromi , Kawata Ryo , Kinoshita Ichita , Higashino Masaaki , Terada Tetsuya , Haginomori Shin-Ichi , Tochizawa Takeshi 
Published: April 2022

Purpose This study investigated the characteristics, diagnosis, and treatment of Warthin tumors (WTs) to explore the possibility of managing patients by observation. Methods We reviewed the records of 1167 patients with benign parotid tumors who were seen in our department between September 1999 and April 2021. Among them, 387 cases were WT and 668 cases were pleomorphic adenoma. We evaluated preoperative diagnoses of WT by symptoms/signs, fine-needle aspiration cytology (FNAC), imaging, such as ultrasonography and magnetic resonance imaging, and technetium-99m pertechnetate (Tc-99m) scintigraphy. Fisher’s exact test and the Mann–Whitney U test were used in statistical analyses. Results Warthin tumors were treated by surgery in 238 cases and follow-up in 149 cases. The 238 patients were diagnosed as WT at the final pathology after surgery. Among them, 172 patients (72.3%) were determined as benign histological type by preoperative FNAC; in these 172 patients, 170 (71.4%) were correctly diagnosed as WT in the final pathology. Preoperative Tc-99m scintigraphy was performed in 69 patients diagnosed with WT by final pathology or FNAC, and the positive rate of Tc-99m scintigraphy in WT was 75.4%. Conclusions Combining FNAC and Tc-99m scintigraphy, as well as considering clinical findings, enables the diagnosis of WT in most cases. In particular, WT is more common in the elderly, grows more slowly, and is less likely to be malignant. Therefore, if WT can be diagnosed preoperatively with a high rate of correct diagnosis, it could be an accurate and effective means of managing patients through follow-up without surgery.
Thermally and organomodified montmorillonite as effective regulators of the structure formation process in polypropylene/polystyrene blends
Authors: Budash Yurii , Rezanova Natalia , Plavan Viktoriia , Rezanova Viktoriia 
Published: April 2022

The influence of the concentration of thermally and organomodified montmorillonite on the processes of structure formation in a blend of polypropylene/polystyrene (PP/PS) was studied. It is established that in nanofilled compositions, as well as in the original, is formed a microfibrillar structure, the dimensional characteristics of which depend on the content of the additive and the method of its modification. The investigated clays by content (0.2–2.0) wt. % by weight of polypropylene have a compatibilizing effect in the blend of PP/PS, which reduces the average diameter of microfibers by 1.6 times and increases the homogeneity of their distribution by diameter: statistical indicators decrease (standard deviation, variance, coefficient of variation). The modifying effect of thermally modified clay is higher—the improvement of the dimensional characteristics of PP microfibers is achieved at its minimum content in the blend (0.2 wt. %). The formation of anisotropic PP structures in the PS matrix and the relaxation of the accumulated stresses at the exit of the molding hole is the main factor that causes high values of the coefficient of swelling of the extrudates (4.0–7.7). The change in the microstructure of the extrudates of nanofilled systems during spinning depends on the composition of the blend and the method of modification of montmorillonite. The average diameters of microfibers decrease from 2.2 μm (in the original blend) to (1.3–2.0) μm (in three-component) depending on the content of additives. The ability to regulate the microstructure of incompatible polymer blends by introducing additives of thermally and organomodified montmorillonite will contribute to the creation of nanocomposites with controlled morphology, as well as new fine-fiber materials with improved filtering characteristics.
Adalimumab-Adbm: The First Interchangeable Biosimilar for the Treatment of Inflammatory Diseases
Authors: Bhat Shubha , Patel Maitri , Duly Kristine , Choi David 
Published: April 2022

Objective The objective of the study was to review the pharmacologic and clinical profile of adalimumab-adbm (BI 695501), the first interchangeable biosimilar for treatment of inflammatory diseases. Data Sources A PubMed search was conducted from inception to December 2021 using the keywords BI 695501 and adalimumab-adbm. Information was also obtained from published abstracts and package inserts. Study Selection and Data Extraction Phase 1, 2 and 3 studies plus relevant literature on adalimumab-adbm pharmacologic and clinical profile were reviewed. Data Synthesis: Adalimumab-adbm approval was based on a series of phase 3 VOLTAIRE trials, which evaluated the biosimilar’s efficacy and safety in the treatment of moderate to severe Crohn’s disease, rheumatoid arthritis, and psoriasis. Interchangeability status was granted based on data from the VOLTAIRE-X trial. The VOLTAIRE and VOLTAIRE-X studies demonstrated comparable efficacy and safety between adalimumab-adbm and reference adalimumab. Common adverse events included infections and injection site reactions. Similar to reference adalimumab, adalimumab-adbm contains black box warnings related to serious infections and malignancy. Relevance to Patient Care and Clinical Practice Adalimumab-adbm is the first interchangeable biosimilar to be approved for inflammatory diseases and has the potential to improve patient access to treatment while decreasing medication-related costs. However, it will not be commercially available for patient use until 2023 and its adoption into clinical practice may face potential barriers seen with other biosimilars. Conclusion As an interchangeable biosimilar with comparable efficacy and safety to reference adalimumab, adalimumab-adbm is an important advance toward cost-effective management of inflammatory diseases.
Arteriovenous fistula self-care behaviors in patients receiving hemodialysis treatment: Association with health literacy and self-care agency
Authors: Bulbul Elif , Yildiz Ayvaz Meryem , Yeni Tugba , Turen Sevda , Efil Sevda 
Published: April 2022

Background: Arteriovenous fistula-related self-care behaviors, self-care agency and health literacy are important for vascular access patency, which is vital in the continuation of hemodialysis treatment. The purpose of this study was to determine the arteriovenous fistula-related self-care behaviors of patients receiving chronic hemodialysis treatment and the relationship between these behaviors and their health literacy and self-care agency levels. Methods: In this descriptive correlational study, the data were collected from 216 chronic hemodialysis patients. Results: The rate of the patients who had good self-care behaviors levels was 83.96%. The sociodemographic variables that were significantly related to AVF-related self-care behaviors were education, employment status and age. It was found that the patients who had had AVF for a longer time had better self-care behaviors regarding their management of symptoms and findings ( p < 0.05). As the self-care agency of the patients ( r = 0.612, p < 0.001) and their health literacy ( r = 0.421, p < 0.001) increased, their AVF-related self-care behaviors also increased. Conclusion: Age, education status, health literacy and self-care agency were identified to affect AVF-related self-care behaviors.
Effect of kidney transplantation activity on arteriovenous fistula use in prevalent haemodialysis patients: A registry-based study
Authors: Roca-Tey Ramon , Comas Jordi , Tort Jaume 
Published: April 2022

Background: Kidney transplantation (KT) is considered to be the best kidney replacement therapy (KRT) option for most end-stage kidney disease (ESKD) patients. Arteriovenous fistula (AVF) is considered to be the best vascular access (VA) for most haemodialysis (HD) patients. In this study, we investigated the effect of KT activity on AVF use in prevalent HD patients. The probability of receiving a kidney graft (KTx) over time, depending on the first VA used to start the HD program, was also evaluated. Methods: Data from the Catalan Registry of prevalent patients on KRT by either KT or HD were examined over a 20-year period (1997–2017). Results: The percentage of prevalent ESKD patients with a functioning KTx increased from 40.5% in 1997 to 57.0% in 2017 and, conversely, the percentage of AVF utilisation in HD patients decreased from 86.0% to 63.2% during the same period (for both comparisons, p < 0.001). This inverse relationship was also demonstrated in other countries and regions worldwide by performing a simple linear regression analysis ( R2 = 0.4974, p = 0.002). The probability of prevalent patients dialysed through an AVF in Catalonia was independently associated with the percentage of functioning KTx among KRT population, after adjusting by age, gender, primary kidney disease, time on KRT, cardiovascular disease and type of HD Unit. Incident patients starting HD through an AVF had a significantly higher probability of receiving a KTx over time in comparison to patients who initiated HD through a catheter (hazard ratio 1.68 [95% confidence interval: 1.41–2.00], p < 0.001). Conclusions In addition to some demographical and clinical characteristics of patients and type of HD Unit, KT activity can be a determining factor in AVF use in prevalent HD patients. Starting an HD programme through an AVF is independently associated with a greater probability of receiving a KTx as compared to starting HD through a catheter.
Regionalism or Multilateralism: Evidence from India
Authors: Kathjoo Umar Nisar , Fazili Asif 
Published: April 2022

With an impasse at Doha round of negotiations, many countries started to change their course of economic liberalization from generic policies of multilateralism to regional trade agreements (RTAs). In this scenario, India plausibly lacks the presence and will of concluding such agreements with some of its major trading partners while being sceptical about the existing ones. Using structural gravity, this study has quantified the impact of country-specific globalization levels and RTAs on international trade among India and its 32 major trading partners. Unlike a plethora of studies employing the gravity model on Indian trade policy issues, we have made use of many recent advancements in gravity modelling. Our methodology robust to the use of intra-national trade data, two alternative estimators, and multiple scenarios naturally addresses the endogeneity issues that are prominent with trade policy variables like RTAs. The empirical results reveal that RTAs have a comparatively strong impact in promoting trade among sample countries. However, country-specific globalization levels measured by the KOF globalization index have a very negligible impact on promoting trade among sample countries. Furthermore, we have obtained very slight asymmetries across the impact of country-specific globalization levels on exports versus imports of mid-income countries with high-income countries. JEL Codes: F1, F14, F15, F60, F68