bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug affinity and targeted delivery: double functionalization of silk spheres for controlled doxorubicin delivery into Her2-positive cancer cells
Authors: Kucharczyk Kamil , Florczak Anna , Deptuch Tomasz , Penderecka Karolina , Jastrzebska Katarzyna , Mackiewicz Andrzej , Dams-Kozlowska Hanna 
Published: March 2020

Abstract
Background
The optimal drug delivery system should be biocompatible, biodegradable, and allow the sustained release of the drug only after it reaches the target cells. Silk, as a natural polymer, is a great candidate for building drug carriers. Genetically engineered silks offer the possibility of functionalization. Previously, we characterized bioengineered silk spheres that were functionalized with H2.1 peptide that selectively delivered a drug to Her2-positive cancer cells. However, drug leakage from the silk spheres showed the need for improved control.

Results
To control the drug loading and release, we designed and produced functional silk (DOXMS2) that contains a DOX peptide with an affinity for doxorubicin. The DOXMS2 spheres showed the decreased release of doxorubicin compared with MS2 particles. Next, the DOXMS2 silk was blended with the H2.1MS1 polymer to improve the control of doxorubicin binding and release into Her2-positive cancer cells. The H2.1MS1:DOXMS2 particles showed the highest doxorubicin-loading capacity and binding per cell, which resulted in the highest cytotoxic effect compared with that of other sphere variants. Since drug release at a pH of 7.4 from the blended H2.1MS1:DOXMS2 particles was significantly lower than from blended spheres without DOXMS2 silk, this indicated that such particles could control the release of the drug into the circulatory system before the carrier reached the tumor site.

Conclusions
This strategy, which is based on the blending of silks, allows for the generation of particles that deliver drugs in a controlled manner.
Patterns of tobacco and e-cigarette use status in India: a cross-sectional survey of 3000 vapers in eight Indian cities
Authors: Sharan Rajeshwar Nath , Chanu Tongbram Malemnganbi , Chakrabarty Tapan Kumar , Farsalinos Konstantinos 
Published: March 2020

Abstract
Background
Tobacco smoking is one of the biggest and avoidable public health threats in the world, especially in low- and middle-income countries. India represents a highly complex public health environment due to the large number of smokers and complexities arising from tobacco use in different forms, including a variety of smokeless tobacco (SLT) products. Electronic cigarettes, an alternative nicotine delivery system with significantly less harmful emissions than smoke, could be an option for those who are unable to achieve smoking abstinence using other available means. This study, which we believe is the first of this kind in India, was conducted to obtain data on the characteristics and tobacco use profile of e-cigarette users (vapers) in India.

Methods
An interview-based survey was performed in the 8 largest metropolitan cities in India using a convenience sampling approach involving a total of 3000 subjects. Inclusion criteria were being a current e-cigarette user and aged 18 years or more. Interviewers were asked to continue recruitment until a total sample of 375 was reached in each target city.

Results
A total of 3000 vapers (81.4% males and 18.6% females, median age 29 years) participated to the study. The majority (80%) were first exposed to nicotine via tobacco smoking, SLT use, or both. Most of the subjects (79%) believed that e-cigarettes were less harmful than smoking. The vast majority of smokers (71.3%) reported smoking cessation (30.0%) or reduction in consumption (41.3%) with the help of e-cigarettes. Similar changes were observed in SLT users. Participants reported minimal side effects and some health benefits after e-cigarette use initiation.

Conclusion
Indian vapers who participated to this study were predominantly smokers and SLT users before e-cigarette use initiation, with the majority subsequently quitting or reducing tobacco use. Minimal side effects of e-cigarette were experienced, while some health benefits were also reported.
“Am I gonna get in trouble for acknowledging my will to be safe?”: Identifying the experiences of young sexual minority men and substance use in the context of an opioid overdose crisis
Authors: Goodyear Trevor , Mniszak Caroline , Jenkins Emily , Fast Danya , Knight Rod 
Published: March 2020

Abstract
Background
North America and other parts of the globe are in the midst of a public health emergency related to opioid overdoses and a highly contaminated illicit drug supply. Unfortunately, there is a substantial gap in our understandings about how this crisis affects key populations not conventionally identified within overdose-related surveillance data. This gap is particularly pronounced for gay, bisexual, and other men who have sex with men (sexual minority men)—a population that experiences substance use-related inequities across adolescence and young adulthood.

Methods
We draw on in-depth semi-structured interviews conducted in 2018 with a diverse sample (N = 50) of sexual minority men ages 15–30 who use substances and live in Vancouver, Canada, to identify how patterns and contexts of substance use are occurring in the context of the opioid overdose crisis.

Results
Our analysis revealed three themes: awareness, perceptions, and experiences of risk; strategies to mitigate risk; and barriers to safer substance use. First, participants described how they are deeply impacted by the contaminated illicit drug supply, and how there is growing apprehension that fatal and non-fatal overdose risk is high and rising. Second, participants described how procuring substances from “trustworthy” drug suppliers and other harm reduction strategies (e.g., drug checking technologies, Naloxone kits, not using alone) could reduce overdose risk. Third, participants described how interpersonal, service-related, and socio-structural barriers (e.g., drug criminalization and the lack of a regulated drug supply) limit opportunities for safer substance use.

Conclusions
Equity-oriented policies and programming that can facilitate opportunities for safer substance use among young sexual minority men are critically needed, including community- and peer-led initiatives, access to low-barrier harm reduction services within commonly frequented social spaces (e.g., Pride, night clubs, bathhouses), nonjudgmental and inclusive substance use-related health services, the decriminalization of drug use, and the provision of a safe drug supply.
Unusually persistent Gαi-signaling of the neuropeptide Y2 receptor depletes cellular Gi/o pools and leads to a Gi-refractory state
Authors: Ziffert Isabelle , Kaiser Anette , Babilon Stefanie , Mörl Karin , Beck-Sickinger Annette G. 
Published: March 2020

Abstract
Background
A sensitive balance between receptor activation and desensitization is crucial for cellular homeostasis. Like many other GPCR, the human neuropeptide Y2 receptor (hY2R) undergoes ligand dependent activation and internalization into intracellular compartments, followed by recycling to the plasma membrane. This receptor is involved in the pathophysiology of distinct diseases e.g. epilepsy and cancer progression and conveys anorexigenic signals which makes it an interesting and promising anti-obesity target. However, Y2R desensitization was observed after daily treatment with a selective PYY13–36 analog in vivo by a yet unknown mechanism.

Materials
We studied the desensitization and activatability of recycled Y2R in transiently transfected HEK293 cells as well as in endogenously Y2R expressing SH-SY5Y and SMS-KAN cells. Results were evaluated by one-way ANOVA and Tukey post test.

Results
We observed strong desensitization of the Y2R in a second round of stimulation despite its reappearance at the membrane. Already the first activation of the Y2R leads to depletion of the functional cellular Gαi/o protein pool and consequently desensitizes the linked signal transduction pathways, independent of receptor internalization. This desensitization also extends to other Gαi/o-coupled GPCR and can be detected in transfected HEK293 as well as in SH-SY5Y and SMS-KAN cell lines, both expressing the Y2R endogenously. By overexpression of chimeric Gαqi proteins in a model system, activation has been rescued, which identifies a critical role of the G protein status for cellular signaling. Furthermore, Y2R displays strong allosteric coupling to inhibitory G proteins in radioligand binding assays, and loses 10-fold affinity in the G protein-depleted state observed after activation, which can be largely abrogated by overexpression of the Gαi-subunit.

Conclusion
The unusually persistent Gαi-signaling of the Y2R leads to a state of cellular desensitization of the inhibitory Gαi-pathway. The strong allosteric effects of the Y2R-Gαi-interaction might be a mechanism that contributes to the burst of Gαi-signaling, but also serves as a mechanism to limit the Y2-mediated signaling after recycling. Thus, the cell is left in a refractory state, preventing further Gαi-signaling of the Y2R itself but also other Gαi/o-coupled receptors by simply controlling the repertoire of downstream effectors.

Graphical abstract
IL-9 and IL-9-producing cells in tumor immunity
Authors: Wan Jie , Wu Yinqiu , Ji Xiaoyun , Huang Lan , Cai Wei , Su Zhaoliang , Wang Shengjun , Xu Huaxi 
Published: March 2020

Abstract
Interleukin (IL)-9 belongs to the IL-2Rγc chain family and is a multifunctional cytokine that can regulate the function of many kinds of cells. It was originally identified as a growth factor of T cells and mast cells. In previous studies, IL-9 was mainly involved in the development of allergic diseases, autoimmune diseases and parasite infections. Recently, IL-9, as a double-edged sword in the development of cancers, has attracted extensive attention. Since T-helper 9 (Th9) cell-derived IL-9 was verified to play a powerful antitumor role in solid tumors, an increasing number of researchers have started to pay attention to the role of IL-9-skewed CD8+ T (Tc9) cells, mast cells and Vδ2 T cell-derived IL-9 in tumor immunity. Here, we review recent studies on IL-9 and several kinds of IL-9-producing cells in tumor immunity to provide useful insight into tumorigenesis and treatment.

Graphical abstract
Inpatient mortality in transition-aged youth with rheumatic disease: an analysis of the National Inpatient Sample
Authors: Jensen Paul T. , Koh Keumseok , Cash Rebecca E. , Ardoin Stacy P. , Hyder Ayaz 
Published: March 2020

AbstractBackgroundTransition from pediatric to adult care is a vulnerable time for youth with chronic diseases. In youth with rheumatic disease, studies show high rates of loss to follow up and increased disease activity. However, mortality data are lacking. In this study, we assessed whether transitional age is a risk factor for inpatient mortality.MethodsWe analyzed the 2012–2014 National Inpatient Sample database, a representative sample of discharges in the United States. Individuals with rheumatic diseases were identified by International Statistical Classification of Disease – 9 (ICD-9) codes at time of discharge. Youth were categorized into three age groups: pre-transitional (11–17), transitional (18–24) and post transitional (25–31). We fitted univariable and multivariable logistic regression models to assess whether transitional age was a risk factor for inpatient mortality.ResultsThere were 30,269 hospital discharges which met our inclusion criteria of diagnosis and age. There were 195 inpatient deaths (0.7%). The most common causes of death were infection (39.5%), pulmonary disease (13.8%), and cardiac disease (11.2%). The Odds ratio for inpatient mortality of a transitional-aged individual was 1.18 compared to controls (p = 0.3). Black race (OR = 1.4), male sex (OR = 1.75), and a diagnosis of systemic sclerosis (OR = 4.81) or vasculitis (OR = 2.85) were the greatest risk factors of inpatient mortality.ConclusionTransitional age was not a risk factor for inpatient mortality in this study. We did identify other risk factors other than age. Further studies are required to assess if there is an increased risk of mortality in outpatients of the transitional age group.
DDX5 potentiates HIV-1 transcription as a co-factor of Tat
Authors: Sithole Nyaradzai , Williams Claire A. , Abbink Truus E. M. , Lever Andrew M. L. 
Published: March 2020

Abstract
Background
HIV-1 does not encode a helicase and hijacks those of the cell for efficient replication. We and others previously showed that the DEAD box helicase, DDX5, is an essential HIV dependency factor. DDX5 was recently shown to be associated with the 7SK snRNP. Cellular positive transcription elongation factor b (P-TEFb) is bound in an inactive form with HEXIM1/2 on 7SK snRNP. The Tat/P-TEFb complex is essential for efficient processivity of Pol II in HIV-1 transcription elongation and Tat competes with HEXIM1/2 for P-TEFb. We investigated the precise role of DDX5 in HIV replication using siRNA mediated knockdown and rescue with DDX5 mutants which prevent protein–protein interactions and RNA and ATP binding.

Results
We demonstrate a critical role for DDX5 in the Tat/HEXIM1 interaction. DDX5 acts to potentiate Tat activity and can bind both Tat and HEXIM1 suggesting it may facilitate the dissociation of HEXIM1/2 from the 7SK-snRNP complex, enhancing Tat/P-TEFb availability. We show knockdown of DDX5 in a T cell line significantly reduces HIV-1 infectivity and viral protein production. This activity is unique to DDX5 and cannot be substituted by its close paralog DDX17. Overexpression of DDX5 stimulates the Tat/LTR promoter but suppresses other cellular and viral promoters. Individual mutations of conserved ATP binding, RNA binding, helicase related or protein binding motifs within DDX5 show that the N terminal RNA binding motifs, the Walker B and the glycine doublet motifs are essential for this function. The Walker A and RNA binding motifs situated on the transactivation domain are however dispensable.

Conclusion
DDX5 is an essential cellular factor for efficient HIV transcription elongation. It interacts with Tat and may potentiate the availability of P-TEFb through sequestering HEXIM1.
Diasporic medical tourism: a scoping review of quantitative and qualitative evidence
Authors: Mathijsen Aneta , Mathijsen François Pierre 
Published: March 2020

Abstract
Background
There is a growing recognition of the significance of the diasporic dimension of medical travel. Explanations of medical tourism are increasingly presented in a wider context of transnationalism, diaspora and migration. Yet diaspora and cross-border travellers rarely get through the broader narrative of medical travel.

Objective
Our aim in this scoping review was to extend the current knowledge on the emerging subject of diasporic travels for medical purposes. Specifically, we reviewed the existing literature on what is known about the determinants and motivational factors of diasporic medical tourism; its geographic scope and its quantitative estimation.

Methods
Using a scoping review methodology, we conducted the search in seven electronic databases. It resulted in 210 records retrieved. Ultimately, 28 research papers and 6 non-research papers (published between 2002 and 2019) met the following criteria: 1) focus on healthcare and health-related practices, 2) transnational perspective, 3) healthcare consumption in the country of origin (homeland) while being a resident of another country, 4) published in English.

Results
The findings from our review highlighted the importance of diasporic medical patients who had been researched and analysed on four continents. Even though quantitative evidence has been scarce, the data analysed in the scoping review pointed to the existence of non-negligible level of diasporic medical tourism in Northern America, and in Europe. Various motivational factors were enumerated with their frequency of occurrence: medical culture (12), time availability (“by the way of being home”) (9), communication (6), dissatisfaction with the current system (6), healthcare insurance status (5), quality of healthcare (5), second opinion (3), and value for money (3).

Conclusion
Diasporic medical tourists constitute an attractive segment of consumers that is still not well understood and targeted. They are part of transnational communities that cultivate the links between the two nations. They simultaneously participate in bi-lateral healthcare systems via return visits which impact the health systems of sending and receiving countries in a substantial way. In the current globalised, connected and migratory context, transnationalism seems to represent an answer to many local healthcare-related barriers. Sending and receiving countries have put in place an array of programmes and policies addressed to the diasporic medical travellers.
Exploring the challenges and opportunities towards optimal breastfeeding in Ethiopia: a formative qualitative study
Authors: Gebremariam Kidane Tadesse , Zelenko Oksana , Hadush Znabu , Mulugeta Afework , Gallegos Danielle 
Published: March 2020

AbstractBackgroundBreastfeeding, particularly exclusive breastfeeding, is essential to ensure the short- and long-term health of infants and mothers. Sub-optimal breastfeeding practices currently take place in low income countries contributing to morbidity and mortality. This research explored the challenges and opportunities around exclusive breastfeeding in a large city in Ethiopia to inform a larger breastfeeding intervention.MethodsFathers and mothers who had children less than 2 years of age, and who could speak, and understand Tigrigna were recruited from two health centres located in Mekelle, Ethiopia. Two focus group discussions (FGDs) with fathers and two FGDs with mothers (n = 42) were conducted using a semi-structured interview guide to explore the challenges and opportunities related to breastfeeding. Discussions were audio-recorded and transcribed in Tigrigna and translated to English. The data were manually analysed using thematic analysis, generating open codes which were grouped to form themes.ResultsFour themes with 11 sub-themes emerged. The themes identifies were: conflicted emotions on the birth of baby (feeling happy and feeling worried); perspectives on intergenerational approaches (old-fashioned beliefs of grandparents and the power of science, breastfeeding in public, breastfeeding knowledge); gender roles as barriers and enablers (the burden on women, changes in men’s roles and the financial status of the household); the role of healthcare (delivery of health information to parents, the role of health care providers and perceptions of inadequate milk supply).ConclusionParents reported a range of opportunities with respect to breastfeeding, including the power of a scientific approach, the positive role of healthcare, and shifts within gender roles that maximized the potential support from fathers. However, there remains a tension between the beliefs of older generations and current best-practice. Parents continue to need ongoing support in order to practice optimal breastfeeding.
Incidence and influence of prosthesis-patient mismatch after reoperative aortic valve replacement: a retrospective single-center study
Authors: Tsubota Hideki , Sakaguchi Genichi , Marui Akira 
Published: March 2020

Abstract
Background
Reoperative aortic valve replacement (AVR) is associated with increased mortality compared with initial surgery, and a smaller valve might be implanted during repeat AVR (re-AVR; AVR after prior AVR). We describe the clinical outcomes and incidence of prosthesis-patient mismatches (PPM) after reoperative AVR.

Methods
Among 113 patients who underwent reoperative AVR between 2007 and 2018, 44 underwent re-AVR and 69 underwent a first replacement of a diseased natural valve after any cardiac surgery except AVR (primary AVR). We then compared early and late outcomes, the impact of re-AVR on the effective orifice areas (EOA), and the incidence and influence of PPM on reoperative AVR.

Results
Hospital mortality was 2.7%, and the overall 1-, 3-, and 5-year survival rates were 95, 91 and 86%, respectively. The reference EOA of the newly implanted valve was smaller than that of the previous valve (1.4 ± 0.3 vs. 1.6 ± 0.3 cm2, p < 0.01). The mean pressure gradient was greater (15.2 ± 6.4 vs. 12.7 ± 6.2 mmHg, p = 0.04) and indexed EOA was smaller (0.92 ± 0.26 vs. 1.06 ± 0.36 cm2/m2, p = 0.04) during re-AVR than primary AVR, whereas the incidence of PPM was similar (38.7% vs. 34.8%, p = 0.87) between the groups.

Conclusions
The clinical outcomes of reoperative AVR were acceptable. Although the reference EOA of new implanted valves was smaller than that of previous valves, re-AVR did not increase the incidence of PPM. These findings might serve as a guide for future decisions regarding the surgical approach to treating degenerated prosthetic valves.
Pien Tze Huang alleviate the joint inflammation in collagen-induced arthritis mice
Authors: Deng YongQi , Luo Hui , Shu Jun , Shu Haiyang , Lu Cheng , Zhao Ning , Geng Yun , He Xiaojuan , Lu Aiping 
Published: March 2020

Abstract
Background
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Pien Tze Huang (PZH) is a Chinese patent medicine with anti-inflammatory and immunomodulatory effects. However, whether PZH could be used in RA therapy is still unknown. Therefore, this study aimed to explore the therapeutic effect and the potential mechanism of PZH on collagen-induced arthritis (CIA) mice.

Methods
Male DBA/1J mice were used to establish an animal model of CIA and then treated with different doses of PZH for 4 weeks. The therapeutic effect of PZH on CIA mice was evaluated by arthritis score, pathological staining, and detecting the levels of inflammatory factors in serum and joints. To investigate its possible mechanism, the activity of NF-κB signaling pathway, NLRP3 inflammasome and the level of A20 were detected.

Results
The results showed that PZH could alleviate the erythema and swelling of hind paws of CIA mice, improve the pathological conditions of joint and decrease the production of IL-1β, IL-6 and IL-17 in serum and joints. Furthermore, PZH could significantly inhibit the activity of NF-κB signaling pathway and NLRP3 inflammasome in the ankle joint of CIA mice compared with the model group. It also increased the level of A20 in the ankle joint of CIA mice.

Conclusion
This study indicated that PZH could alleviate the joint inflammation of CIA mice, and the mechanism might be related to the regulation of NF-κB signaling pathway and NLRP3 inflammasome.