bluuebunny/crossref_metadata_2025 huggingface dataset:
A Somatostatin Receptor Subtype-3 (SST3) Peptide Agonist Shows Antitumor Effects in Experimental Models of Nonfunctioning Pituitary Tumors
Authors: Vázquez-Borrego Mari C. , Gupta Vandana , Ibáñez-Costa Alejandro , Gahete Manuel D. , Venegas-Moreno Eva , Toledano-Delgado Álvaro , Cano David A. , Blanco-Acevedo Cristóbal , Ortega-Salas Rosa , Japón Miguel A. , Barrera-Martín Ana , Vasiljevic Alexandre , Hill Jason , Zhang Shengwen , Halem Heather , Solivera Juan , Raverot Gérald , Gálvez María A. , Soto-Moreno Alfonso , Paez-Pereda Marcelo , Culler Michael D. , Castaño Justo P. , Luque Raúl M.
Published: October 2019

Purpose:

Somatostatin analogues (SSA) are efficacious and safe treatments for a variety of neuroendocrine tumors, especially pituitary neuroendocrine tumors (PitNET). Their therapeutic effects are mainly mediated by somatostatin receptors SST2 and SST5. Most SSAs, such as octreotide/lanreotide/pasireotide, are either nonselective or activate mainly SST2. However, nonfunctioning pituitary tumors (NFPTs), the most common PitNET type, mainly express SST3 and finding peptides that activate this particular somatostatin receptor has been very challenging. Therefore, the main objective of this study was to identify SST3-agonists and characterize their effects on experimental NFPT models.

Experimental Design:

Binding to SSTs and cAMP level determinations were used to screen a peptide library and identify SST3-agonists. Key functional parameters (cell viability/caspase activity/chromogranin-A secretion/mRNA expression/intracellular signaling pathways) were assessed on NFPT primary cell cultures in response to SST3-agonists. Tumor growth was assessed in a preclinical PitNET mouse model treated with a SST3-agonist.

Results:

We successfully identified the first SST3-agonist peptides. SST3-agonists lowered cell viability and chromogranin-A secretion, increased apoptosis in vitro, and reduced tumor growth in a preclinical PitNET model. As expected, inhibition of cell viability in response to SST3-agonists defined two NFPT populations: responsive and unresponsive, wherein responsive NFPTs expressed more SST3 than unresponsive NFPTs and exhibited a profound reduction of MAPK, PI3K-AKT/mTOR, and JAK/STAT signaling pathways upon SST3-agonist treatments. Concurrently, SSTR3 silencing increased cell viability in a subset of NFPTs.

Conclusions:

This study demonstrates that SST3-agonists activate signaling mechanisms that reduce NFPT cell viability and inhibit pituitary tumor growth in experimental models that expresses SST3, suggesting that targeting this receptor could be an efficacious treatment for NFPTs.
ЕТАПИ РОЗВИТКУ СИСТЕМИ ВІЙСЬКОВО-МЕДИЧНОГО ПОСТАЧАННЯ В КОНТЕКСТІ ІСТОРІЇ БУДІВНИЦТВА ЗБРОЙНИХ СИЛ УКРАЇНИ
Authors: Shmatenko O.P. , Bilous M. V. , Prikhodko T. V. , Galan O. V. , Trokhymchuk V. V. , Drozdov D. V. , Takhtaulova N. O.
Published: October 2019

Метою роботи є дослідження етапів становлення та розвитку системи військово-медичного постачання в контексті історії будівництва Збройних Сил України.

Матеріали та методи. Для досягнення поставленої мети дослідження проведено огляд вітчизняних наукових джерел та чинної нормативно-правової бази. Під час виконання дослідження використано методи інформаційного пошуку, систематизації, контент-аналізу, порівняння та узагальнення.

Результати та їх обговорення. При проведенні дослідження етапів становлення та розвитку системи військово-медичного постачання в контексті історії будівництва Збройних Сил України, встановлено, що на момент створення Збройних Сил України військово-медична служба та система медичного постачання будувалась з використанням підходів Радянської Армії. З’ясовано, що прийняття оборонної доктрини, зміна економічних засад в країні та обмеженість ресурсів обумовили перехід до медичного забезпечення та постачання медичною технікою та майном за територіальним принципом. Це, в свою чергу, потребувало скорочення чисельності як Збройних Сил України, так і медичної служби до оптимальної кількості. Визначено, що недостатність бюджетного фінансування на протязі всіх років існування Збройних Сил України не дозволила в повному обсязі побудувати ефективну модель медичного постачання та провести технічне переоснащення медичної служби. Проведений ретроспективний аналіз еволюції органів управління медичною службою Збройних Сил України показав, що в періоди 1991-1994 рр. та 2005-2007 рр. існувало дублювання управлінської функції з медичного забезпечення в Міністерстві оборони України та Генеральному штабі Збройних Сил України. При цьому, в період з 1998-2005 рр. управління медичним забезпеченням здійснював єдиний орган управління, що сприяло більш ефективному вирішенню питань медичного забезпечення.

Висновки. В статті проведено дослідження етапів становлення та розвитку системи військово-медичного постачання в контексті історії будівництва Збройних Сил України. Також визначено, що на сучасному етапі реалізується принцип єдиного органу управління медичною службою, що відповідає стандартам НАТО. Станом на сьогодні, розвиток системи медичного постачання Збройних Сил України орієнтований на інтеграцію у єдину ефективну систему логістичного забезпечення ЗС України, яка функціонує відповідно до норм та стандартів Альянсу. Таким чином, для вибору науково-обґрунтованої моделі військово-медичного постачання в сучасних реаліях необхідним є узагальнення історичного досвіду формування системи постачання медичним майном Збройних Сил України. Отже, предметом нашого подальшого дослідження є визначення еволюційних етапів розвитку управління потоковими процесами у системі медичного постачання Збройних Сил України.
GÖYNÜKLÜ BİR TARİH YAZICISI: ŞIKK-I SANİ DEFTERDARI VE HAZİNE-İ BİRUN KÂTİBİ AHMED BİN MAHMUD EFENDİ
Authors: YILDIZ Hakan
Published: October 2019

Bu çalışmada, XVII. yüzyılın ikinci yarısı ile XVIII.
yüzyılın ilk yarısında yaşamış bir Osmanlı maliye bürokratı olan Göynüklü Ahmed
Efendi’nin hayatı ve devlet hizmeti ele alınmıştır. Müellifin hayatı ile ilgili
tespit edilebilen kaynaklar, arşiv belgeleri ve araştırmalar titizlikle
incelenmiştir. Bu karşılaştırmalı inceleme sırasında, konu ile ilgili daha önce
yapılan araştırmalarda görülen hatalar düzeltilmiş ve eksiklikler tamamlanmıştır.
Bunun yanında müellifin değişik konulara ait notlarını bir araya getirdiği
eseri "Mecmua"dan
istifade edilerek, hayatı ve devlet hizmetine dair bazı yeni ve teyit edici
bilgilere de yer verilmiştir. Bu suretle Ahmed Efendi’nin hayatı, doğru ve
kapsamlı şekilde ortaya konulmaya çalışılmıştır.
TÜRKİYE’DE KAMU HARCAMALARI VE VERGİLERİN İÇ GÖÇ ÜZERİNDEKİ ETKİLERİ
Authors: DÖKMEN Gökhan , TOSUNER Furkan
Published: October 2019

Nüfus
hareketlerinin kalkınma süreci başta olmak üzere birçok alanda önemli etkileri
vardır. Göç, bireysel çıkar motivasyonu ile hareket edildiği varsayımı altında
göçmen için faydalı olsa da, bir bütün olarak topluma faydalı olmayabilir.
Özellikle gelişmekte olan ülkelerde göç, şehirlerin kalabalıklaşmasına,
işsizlik sorunlarına ve bölgesel dengesizliklere neden olabilmektedir. Dolayısıyla
iç göçün belirleyicileri incelenmesi gerekli bir konudur. Bu çalışmada, kamu
harcamaları ve vergilerin iç göç üzerindeki etkileri, Türkiye örneklemi
bağlamında ele alınmıştır. Yapılan dinamik panel veri analiz sonuçlarına göre,
kamu harcamaları ile iç göç arasında istatistiksel olarak anlamlı bir ilişki
kurulamamış iken; vergi gelirleri ile iç göç arasında ise negatif bir ilişki
tespit edilmiştir. Kamu harcamalarına fonksiyonel sınıflandırma açısından
bakıldığında ise güvenlik ve savunma harcamaları ile net göç hızı arasında ters
yönlü bir ilişki bulunmuştur.
BÖLGESEL KALKINMADA SOSYAL SERMAYENİN ROLÜ: ZONGULDAK’TA BİR ALAN ARAŞTIRMASI
Authors: ÇEŞTEPE Hamza , GEMİCİOĞLU Alican
Published: October 2019

Sosyal sermaye kavramı son dönemlerde siyaset bilimi,
sosyoloji gibi bilim dallarıyla birlikte iktisatta da yaygın bir şekilde
kullanılmaya başlanmıştır. Bu bağlamda, kalkınmanın ve özellikle bölgesel
kalkınmanın sağlanmasında önemli bir araç olarak kabul edilen sosyal sermaye
ile ilgili çalışmaların sayısı artmaktadır. Bu çalışmada, sosyal sermaye düzeyi
Zonguldak ili örneğinde belirlenmeye çalışılmıştır. Bu amaçla, Zonguldak il
merkezinde bir örnek kütleye alan araştırması uygulanmıştır. Alan
araştırmasında kullanılan anket, literatürde sosyal sermayeyi belirlemede
kullanılan göstergelerden yararlanılarak 5’li likert ölçeği formatında
hazırlanmıştır. Bu göstergeler güven endeksi, network endeksi ile karşılıklı
yardımlaşma ve ortak işbirliği endeksi olarak belirlenmiştir. Alan araştırması
sonuçlarına göre, Zonguldak’ta sosyal sermaye düzeyinin genel olarak düşük
düzeyde olduğu, bunun da bölgesel kalkınma düzeyini olumsuz etkilediği
söylenebilir. İlin kalkınmışlık düzeyini artırmak için, sosyal ve beşeri
sermayeyi geliştirici politikaların uygulamaya geçirilmesi gerekmektedir.
The Anonymous Subject of Life—Some Philosophical, Psychological, and Religious Considerations
Authors: Johnson David W.
Published: October 2019

One of the hallmarks of the Japanese psychiatrist and philosopher Kimura Bin’s (b. 1931) philosophical approach is the conversion of ordinary words into philosophical concepts. Here we focus on the way he appropriates the Japanese words onozukara and mizukara, ordinary terms associated, respectively, with things that occur naturally, spontaneously, or by themselves, and those that come from oneself. This re-reading of these terms as philosophical concepts furnishes an interpretive frame that brings together and makes sense of large and important concepts in philosophy and psychology such as self and nature, perception and sensation, collective subjectivity and individual subject, schizophrenia and self-realization. His appropriation of these two Japanese terms also uncovers a general and impersonal form of subjectivity that underlies our experience of ourselves as individuated subjects and stands at the center of his philosophical and psychological investigations into these phenomena.
Metaphorical Bridges
Authors: Benjamins Jacob
Published: October 2019

This study considers Paul Ricoeur’s theory of discourses within the context of a phenomenology of religion. I focus on the eighth study of La métaphore vive, wherein Ricoeur explores the possibility of interanimation between speculative and poetic discourses. While Ricoeur is willing to consider the interactions between religious and philosophical discourse in a number of essays, he does not develop the further possibility of the interanimation between religious and speculative thought. I take up this unexplored possibility by suggesting that metaphors are capable of slipping between discourses and animating speculative and religious discourses. Specifically, I use Jean-Louis Chrétien’s metaphor of “wounding” as a case study wherein the phenomenal form of paradox defines one meaning of wounding, while another meaning is connected to a poetic expression that refers to our belonging in the world. Together, the two meanings of the metaphor enliven Chrétien’s phenomenology of religion.
Why the Testimonium Taciteum Is Authentic: A Response to Carrier
Authors: Blom Willem J. C.
Published: October 2019

The reference to Christ in Tacitus’ Annales is one of the earliest references to Jesus by a non-Christian author. Although this so-called “Testimonium Taciteum” is generally accepted as authentic, arguments against the authenticity of the passage given by Richard Carrier have not yet received a thorough response. In this article, I will argue that the arguments against authenticity of the Testimonium Taciteum do not rest on solid ground, nor does the alternative interpretation of the passage by Carrier. On the other hand, it is probable that Tacitus referred in his passage to the persecution of Christians, although that persecution may have been less connected with the fire of Rome than is commonly suggested. There are also four arguments that favour the authenticity of the Testimonium.
Evagrius of Pontus on Exodus and the Virtues
Authors: White Devin L.
Published: October 2019

In On Prayer 1-4, Evagrius of Pontus reads the incense described in Exodus 30:34-37 as an allegorical type of the four cardinal virtues. This essay explains the logic of Evagrius’s interpretation, situating his argument in a longstanding philosophical debate about the interrelationship of the virtues. By reading the incense as virtue, Evagrius joins both Gregory of Nazianzus and Gregory of Nyssa in interpreting Exodus as a source for virtue theory, as well as several ancient philosophers who explained the virtues and their interrelation by comparing them to physical substances combined in a mixture. Central to Evagrius’s argument is the compound ancient philosophers called a “juxtaposition” (σύνθεσις), the use of which term shows Evagrius’s knowledge of a well-attested hexaplaric variant in Exod 30:35. In sum, authorized by his text of Exodus, Evagrius suggests the virtues relate to each other in the same fashion that the ingredients of a σύνθεσις relate to each other.
Rindenzettel und Schriftverkehr
Authors: Ott Michael R.
Published: October 2019

This is an essay about media and communication, especially about the post and its effects on collective poetical production in the seventeenth century. Sigmund von Birken and the “Pegnitz Order of Flowers” take centre stage. As their members were widely scattered, literary societies relied on written communication and postal services. In their texts, Sigmund von Birken and others devised pastoral worlds in which these members may meet virtually and write simultaneously (in particular on trees). These pastoral worlds, the present author argues, fashion a utopian space in which the restrictions of postal communication are suspended.
Political Thinking on Kingship in Democratic Athens
Authors: Mitchell Lynette
Published: October 2019

Democratic Athens seems to have been the first place in the Greek world where there developed systematically a positive theorising of kingship. Initially this might seem surprising, since the Athenians had a strong tradition of rejecting one-man-rule. The study of kingship among the political thinkers of the fifth and fourth century has not received much scholarly attention until recent years, and particularly not the striking fact that it was democratic Athens, or at least writers directing themselves to an Athenian democratic audience, that produced a positive theorising of kingship. The aim of this essay, then, is not only to show how the political language around kingship became a way of forming definitions of what democracy was and was not, but also (more significantly), among some fourth-century intellectuals, of shaping new ideas about what it could be.
Francisco Suárez and the Complexities of Modernity
Authors: Senent-De Frutos Juan Antonio
Published: October 2019

I present here a key to reading the work of Jesuit thinker Francisco Suárez in the context of the plurality and complexity of modernity. I show the main configuration that defines modernity in its hegemonic version, as well as its limitations. From there, I propose how Suárez’s work can be understood from the perspective of its own Ignatian and Jesuit spiritual framework and in relation to the development of modernity. Although a dominant version of modernity has historically prevailed, modernity cannot be understood as a uniform process but one that has been articulated and expressed in different civilizing missions since the Renaissance. One modern way of responding to the socio-cultural challenges of the Renaissance was articulated by the Society of Jesus. I believe that in light of what I term an “Ignatian modernity,” we can better understand Suárez’s intellectual mission, its historical virtuality, and the possibilities marginalized by hegemonic modernity.
A Variable-Correlation Model to Characterize Asymmetric Dependence for Postprocessing Short-Term Precipitation Forecasts
Authors: Li Wentao , Wang Quan J. , Duan Qingyun
Published: October 2019

Statistical postprocessing methods can be used to correct bias and dispersion error in raw ensemble forecasts from numerical weather prediction models. Existing postprocessing models generally perform well when they are assessed on all events, but their performance for extreme events still needs to be investigated. Commonly used joint probability postprocessing models are based on the correlation between forecasts and observations. Because the correlation may be lower for extreme events as a result of larger forecast uncertainty, the dependence between forecasts and observations can be asymmetric with respect to the magnitude of the precipitation. However, the constant correlation coefficient in the traditional joint probability model lacks the flexibility to model asymmetric dependence. In this study, we formulated a new postprocessing model with a decreasing correlation coefficient to characterize asymmetric dependence. We carried out experiments using Global Ensemble Forecast System reforecasts for daily precipitation in the Huai River basin in China. The results show that, although it performs well in terms of continuous ranked probability score or reliability for all events, the traditional joint probability model suffers from overestimation for extreme events defined by the largest 2.5% or 5% of raw forecasts. On the contrary, the proposed variable-correlation model is able to alleviate the overestimation and achieves better reliability for extreme events than the traditional model. The proposed variable-correlation model can be seen as a flexible extension of the traditional joint probability model to improve the performance for extreme events.
SDA: a semi-parametric differential abundance analysis method for metabolomics and proteomics data
Authors: Li Yuntong , Fan Teresa W.M. , Lane Andrew N. , Kang Woo-Young , Arnold Susanne M. , Stromberg Arnold J. , Wang Chi , Chen Li
Published: October 2019

Background

Identifying differentially abundant features between different experimental groups is a common goal for many metabolomics and proteomics studies. However, analyzing data from mass spectrometry (MS) is difficult because the data may not be normally distributed and there is often a large fraction of zero values. Although several statistical methods have been proposed, they either require the data normality assumption or are inefficient.

Results

We propose a new semi-parametric differential abundance analysis (SDA) method for metabolomics and proteomics data from MS. The method considers a two-part model, a logistic regression for the zero proportion and a semi-parametric log-linear model for the possibly non-normally distributed non-zero values, to characterize data from each feature. A kernel-smoothed likelihood method is developed to estimate model coefficients and a likelihood ratio test is constructed for differential abundant analysis. The method has been implemented into an R package, SDAMS, which is available at https://www.bioconductor.org/packages/release/bioc/html/SDAMS.html.

Conclusion

By introducing the two-part semi-parametric model, SDA is able to handle both non-normally distributed data and large fraction of zero values in a MS dataset. It also allows for adjustment of covariates. Simulations and real data analyses demonstrate that SDA outperforms existing methods.
Genome-wide identification, expression profiles and regulatory network of MAPK cascade gene family in barley
Authors: Cui Licao , Yang Guang , Yan Jiali , Pan Yan , Nie Xiaojun
Published: October 2019

Background

Mitogen-activated protein kinase (MAPK) cascade is a conserved and universal signal transduction module in organisms. Although it has been well characterized in many plants, no systematic analysis has been conducted in barley.

Results

Here, we identified 20 MAPKs, 6 MAPKKs and 156 MAPKKKs in barley through a genome-wide search against the updated reference genome. Then, phylogenetic relationship, gene structure and conserved protein motifs organization of them were systematically analyzed and results supported the predictions. Gene duplication analysis revealed that segmental and tandem duplication events contributed to the expansion of barley MAPK cascade genes and the duplicated gene pairs were found to undergone strong purifying selection. Expression profiles of them were further investigated in different organs and under diverse abiotic stresses using the available 173 RNA-seq datasets, and then the tissue-specific and stress-responsive candidates were found. Finally, co-expression regulatory network of MAPK cascade genes was constructed by WGCNA tool, resulting in a complicated network composed of a total of 72 branches containing 46 HvMAPK cascade genes and 46 miRNAs.

Conclusion

This study provides the targets for further functional study and also contribute to better understand the MAPK cascade regulatory network in barley and beyond.
Genome-wide identification of small heat-shock protein (HSP20) gene family in grape and expression profile during berry development
Authors: Ji Xiao-Ru , Yu Yi-He , Ni Pei-Yi , Zhang Guo-Hai , Guo Da-Long
Published: October 2019

Background

Studies have shown that HSP20 (heat-shock protein 20) genes play important roles in regulating plant growth, development, and stress response. However, the grape HSP20 gene family has not been well studied.

Results

A total of 48 VvHSP20 genes were identified from the grape genome, which were divided into 11 subfamilies (CI, CII, CIII, CV, CVI, CVII, MI, MII, ER, CP and PX/Po) based on a phylogenetic analysis and subcellular localization. Further structural analysis showed that most of the VvHSP20 genes (93.8%) had no intron or only one intron, while genes that clustered together based on a phylogenetic tree had similar motifs and evolutionarily conserved structures. The HSP20s share a conservedα-crystalline domain (ACD) and the different components of the ACD domain suggest the functional diversity of VvHSP20s. In addition, the 48 VvHSP20 genes were distributed on 12 grape chromosomes and the majority of VvHSP20 genes were located at the proximal or distal ends of chromosomes. Chromosome mapping indicated that four groups of VvHSP20 genes were identified as tandem duplication genes. Phytohormone responsive, abiotic and biotic stress-responsive, and plant development-related cis-elements were identified from the cis-regulatory elements analysis of VvHSP20s. The expression profiles of VvHSP20s genes (VvHSP20–1, 11, 14, 17, 18, 19, 20, 24, 25, 28, 31, 39, 42, and 43) were largely similar between RNA-Seq and qRT-PCR analysis after hydrogen peroxide (H2O2) treatment. The results showed that most VvHSP20s were down-regulated by H2O2 treatment during fruit development. VvHSP20s genes were indeed found to be involved in the grape berry development and differences in their transcriptional levels may be the result of functional differentiation during evolution.

Conclusions

Our results provide valuable information on the evolutionary relationship of genes in the VvHSP20 family, which is useful for future studies on the functional characteristics of VvHSP20 genes in grape.
Evaluation of the surveillance system for invasive meningococcal disease (IMD) in the Netherlands, 2004–2016
Authors: Brandwagt Diederik A. H. , van der Ende Arie , Ruijs Wilhelmina L. M. , de Melker Hester E. , Knol Mirjam J.
Published: October 2019

Background

Enhanced surveillance for confirmed cases of invasive meningococcal disease (IMD) was introduced in the Netherlands in 2003, in which reference laboratory data (NRLBM) are linked with notification data (OSIRIS). The quality of surveillance information is important for public health decision making. Our objective was to describe the system and evaluate it for data completeness and timeliness.

Methods

Cases reported in the surveillance system from 2004 to 2016 were included. For the notification data, we used information on serogroup, vaccination status, mortality, and country of infection as indicators for record completeness. Notification times to regional and national level were calculated using the reported dates available in the notification database.

Results

A total of 2123 cases were reported in the years 2004–2016, of which 1.968 (93%) were reported by the reference laboratory and 1.995 (94%) in the notification system. Of all cases, 1.840 cases (87%) were reported in both systems and could be linked. The serogroup was known in 86% of the notified cases, and was significantly higher (94%) in the years 2013–2016. Information on vaccination status, mortality and country of infection was available in 88, 99 and 97% of notified cases, respectively. Regional notification of cases occurred within one working day for 86% of cases and 98% were notified nationally within three days.

Conclusions

A well performing IMD surveillance system was demonstrated and serogroup completeness has improved over the years. Underlining the need for reporting to both the clinical and laboratory surveillance system remains important to further improve the overall performance in supporting public health response and vaccination policy.
Factors associated with successful vaginal birth after a cesarean section: a systematic review and meta-analysis
Authors: Wu Yanxin , Kataria Yachana , Wang Zilian , Ming Wai-Kit , Ellervik Christina
Published: October 2019

Background

Evidence for the relationship between maternal and perinatal factors and the success of vaginal birth after cesarean section (VBAC) is conflicting. We aimed to systematically analyze published data on maternal and fetal factors for successful VBAC.

Methods

A comprehensive search of Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature, from each database’s inception to March 16, 2018. Observational studies, identifying women with a trial of labor after one previous low-transverse cesarean section were included. Two reviewers independently abstracted the data. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale.

Results

We included 94 eligible observational studies (239,006 pregnant women with 163,502 VBAC). Factors were associated with successful VBAC with the following odds ratios (OR;95%CI): age (0.92;0.86–0.98), obesity (0.50;0.39–0.64), diabetes (0.50;0.42–0.60), hypertensive disorders complicating pregnancy (HDCP) (0.54;0.44–0.67), Bishop score (3.77;2.17–6.53), labor induction (0.58;0.50–0.67), macrosomia (0.56;0.50–0.64), white race (1.39;1.26–1.54), previous vaginal birth before cesarean section (3.14;2.62–3.77), previous VBAC (4.71;4.33–5.12), the indications for the previous cesarean section (cephalopelvic disproportion (0.54;0.36–0.80), dystocia or failure to progress (0.54;0.41–0.70), failed induction (0.56;0.37–0.85), and fetal malpresentation (1.66;1.38–2.01)). Adjusted ORs were similar.

Conclusions

Diabetes, HDCP, Bishop score, labor induction, macrosomia, age, obesity, previous vaginal birth, and the indications for the previous CS should be considered as the factors affecting the success of VBAC.
Case report of oxalate nephropathy in a patient with pancreatic metastases from renal carcinoma
Authors: Purshouse Karin , Chamberlain Sarah , Soares Maria , Tuthill Mark , Protheroe Andrew , Mole David R.
Published: October 2019

Background

Patients with metastatic renal carcinoma frequently have pre-existing renal impairment and not infrequently develop worsening renal function as a complication of their treatment. The presence of pancreatic metastases in patients with metastatic renal carcinoma, often confers a more favourable prognosis and as a consequence this patient group may be exposed to such treatments for more prolonged periods of time. However, the development of renal failure may also be a consequence of the cancer itself rather than its treatment.

Case presentation

We present an 84-year-old patient receiving the tyrosine kinase inhibitor (TKI) pazopanib for metastatic renal carcinoma who developed oxalate nephropathy as a consequence of pancreatic exocrine insufficiency resulting from pancreatic metastases.

Conclusions

This case demonstrates the importance of investigating unexpected toxicities and highlights the potential consequences of pancreatic insufficiency and its sequelae in patients with pancreatic metastases.
Development of interventions for an intelligent and individualized mobile health care system to promote healthy diet and physical activity: using an intervention mapping framework
Authors: Chen Yuling , Wu Fangqin , Wu Ying , Li Jia , Yue Peng , Deng Ying , Lamb Karen V. , Fong Simon , Liu Yisi , Zhang Yan
Published: October 2019

Background

The mortality of coronary heart disease can be largely reduced by modifying unhealthy lifestyles. However, the long-term effectiveness of interventions for modifying unhealthy diet and physical inactivity of patients with coronary heart disease remain unsatisfactory worldwide. This study aims to systematically design a set of theory-based and evidence-based, individualized, and intelligent interventions for promoting the adoption and maintenance of a healthy diet and physical activity level in patients with coronary heart disease.

Methods

The interventions will be delivered by a mobile health care system called Individualized, Intelligent and Integrated Cardiovascular Application for Risk Elimination. Three steps of the intervention mapping framework were used to systematically develop the interventions. Step 1: needs assessment, which was carried out by a literature review, in-depth interviews and focus group discussions. Step 2: development of objective matrix for diet and physical activity changes, based on the intersection of objectives and determinants from the Contemplation-Action-Maintenance behavior change model. Step 3: formulation of evidence-based methods and strategies, and practical applications, through a systematic review of existing literature, research team discussions, and consultation with multidisciplinary expert panels.

Results

Three needs relevant to content of the intervention, one need relevant to presentation modes of the intervention, and four needs relevant to functional features of the application were identified. The objective matrix includes three performance objectives, and 24 proximal performance objectives. The evidence-based and theory-based interventions include 31 strategies, 61 evidence-based methods, and 393 practical applications.

Conclusions

This article describes the development of theory-based and evidence-based interventions of the mobile health care system for promoting the adoption and maintenance of a healthy diet and physical activity level in a structured format. The results will provide a theoretical and methodological basis to explore the application of intervention mapping in developing effective behavioral mobile health interventions for patients with coronary heart disease.

Trial registration

Chinese Clinical Trial Registry: ChiCTR-INR-16010242. Registered 24 December 2016. http://www.chictr.org.cn/index.aspx
Utilizing a user-centered approach to develop and assess pharmacogenomic clinical decision support for thiopurine methyltransferase
Authors: Nguyen Khoa A. , Patel Himalaya , Haggstrom David A. , Zillich Alan J. , Imperiale Thomas F. , Russ Alissa L.
Published: October 2019

Background

A pharmacogenomic clinical decision support tool (PGx-CDS) for thiopurine medications can help physicians incorporate pharmacogenomic results into prescribing decisions by providing up-to-date, real-time decision support. However, the PGx-CDS user interface may introduce errors and promote alert fatigue. The objective of this study was to develop and evaluate a prototype of a PGx-CDS user interface for thiopurine medications with user-centered design methods.

Methods

This study had two phases: In phase I, we conducted qualitative interviews to assess providers’ information needs. Interview transcripts were analyzed through a combination of inductive and deductive qualitative analysis to develop design requirements for a PGx-CDS user interface. Using these requirements, we developed a user interface prototype and evaluated its usability (phase II).

Results

In total, 14 providers participated: 10 were interviewed in phase I, and seven providers completed usability testing in phase II (3 providers participated in both phases). Most (90%) participants were interested in PGx-CDS systems to help improve medication efficacy and patient safety. Interviews yielded 11 themes sorted into two main categories: 1) health care providers’ views on PGx-CDS and 2) important design features for PGx-CDS. We organized these findings into guidance for PGx-CDS content and display. Usability testing of the PGx-CDS prototype showed high provider satisfaction.

Conclusion

This is one of the first studies to utilize a user-centered design approach to develop and assess a PGx-CDS interface prototype for Thiopurine Methyltransferase (TPMT). This study provides guidance for the development of a PGx-CDS, and particularly for biomarkers such as TPMT.
Economic barriers, evidentiary gaps, and ethical conundrums: a qualitative study of physicians’ challenges recommending HPV vaccination to older gay, bisexual, and other men who have sex with men
Authors: Grace Daniel , Gaspar Mark , Rosenes Ron , Grewal Ramandip , Burchell Ann N. , Grennan Troy , Salit Irving E.
Published: October 2019

Background

The human papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide. Gay, bisexual, and other men who have sex with men (GBM), and GBM living with HIV in particular, are disproportionately impacted by HPV-associated cancers. The HPV vaccine, given early enough in life, may markedly reduce the likelihood of such cancers. In Canada, most provincial insurance programs only cover HPV vaccination for GBM up to the age of 26. Our objective was to understand physicians’ everyday experiences and challenges in recommending HPV vaccination to older GBM patients.

Methods

As part of the HPV Screening and Vaccine Evaluation (HPV-SAVE) Study, we conducted semi-structured interviews with 25 HIV-positive GBM patients who had received anal cancer screening and 15 service providers, including 13 physicians, who had arranged for anal cancer screening in the Canadian provinces of Ontario and British Columbia. In this analysis, we draw upon the 13 physician interviews, which were coded following Grounded Theory.

Results

Physicians strongly supported the HPV vaccine for all GBM and considered it to be important for the management of HIV-related care. However, the overall support for HPV vaccination among physicians did not translate into consistent recommendation practices. There were two overarching factors that limited the strength/frequency of physicians’ vaccine recommendation practices. First, cost/insurance coverage for some older patients impacted if and how the HPV vaccine was discussed. Second, physicians had diverse perspectives on both the prevention and therapeutic benefits of vaccinating older GBM and the reality that national guidelines are incongruent with publicly funded vaccine programs for vaccinating patients over 26 years old. These two interrelated factors have co-produced an apparent economic-evidentiary conundrum for many physicians regarding how and for whom to offer HPV vaccination.

Conclusion

Economic barriers coupled with evidentiary and guideline gaps have created clinical practice challenges for physicians and has resulted in different messages being communicated to some older GBM patients about how important HPV vaccination is for their health.
Doxorubicin-polyglycerol-nanodiamond conjugate is a cytostatic agent that evades chemoresistance and reverses cancer-induced immunosuppression in triple-negative breast cancer
Authors: Yuan Shen-Jun , Xu Yong-Hong , Wang Chao , An Hui-Chao , Xu Hua-Zhen , Li Ke , Komatsu Naoki , Zhao Li , Chen Xiao
Published: October 2019

Background

Triple negative breast cancer (TNBC) has the poorest prognosis of all breast cancer subtypes and is one of the most fatal diseases for women. Combining cytotoxic chemotherapy with immunotherapy has shown great promise for TNBC treatment. However, chemotherapy often leads to the development of chemoresistance and severe systemic toxicity compromising the immune functions that are crucial to anti-TNBC immune therapy. Tumor-induced immunosuppression also poses a great hindrance to efficacious anti-TNBC immunotherapy. Nanomedicine holds great promise to overcome these hurdles.

Results

Doxorubicin-polyglycerol-nanodiamond conjugate (Nano-DOX) was firstly found to be a cytostatic agent to the 4T1 cells and displayed a lower apparent therapeutic potency than DOX. However, the tumor-bearing animals, particularly some key immune cells thereof, showed good tolerance of Nano-DOX as opposed to the severe toxicity of DOX. Next, Nano-DOX did not induce significant upregulation of P-gp and IL-6, which were demonstrated to be key mediators of chemoresistance to DOX in the 4T1 cells. Then, Nano-DOX was shown to downregulate tumor-derived granulocyte-colony stimulating factor (G-CSF) and suppresses the induction and tissue filtration of myeloid-derived suppressor cells (MDSCs) that are the principal effectors of cancer-associated systemic immunosuppression. Nano-DOX also alleviated the phenotype of MDSCs induced by 4T1 cells. Finally, Nano-DOX induced the 4T1 cells to emit damage associated molecular patterns (DAMPs) that stimulated the tumor immune microenvironment through activating key immune effector cells involved in anti-tumor immunity, such as macrophages, dendritic cells and lymphocytes in the tumor tissue.

Conclusions

Nano-DOX is a cytostatic agent with good host tolerance which is capable of evading chemoresistance and reversing cancer-induced immunosuppression both at the systemic level and in the tumor microenvironment in TNBC. Our work presents Nano-DOX as an interesting example that a chemotherapeutic agent in nano-form may possess distinct biochemical properties from its free form, which can be exploited to join chemotherapy with immunotherapy for better treatment of cancer.
pH-triggered endosomal escape of pore-forming Listeriolysin O toxin-coated gold nanoparticles
Authors: Plaza-GA Ismael , Manzaneda-González Vanesa , Kisovec Matic , Almendro-Vedia Víctor , Muñoz-Úbeda Mónica , Anderluh Gregor , Guerrero-Martínez Andrés , Natale Paolo , López Montero Iván
Published: October 2019

Background

A major bottleneck in drug delivery is the breakdown and degradation of the delivery system through the endosomal/lysosomal network of the host cell, hampering the correct delivery of the drug of interest. In nature, the bacterial pathogenListeria monocytogeneshas developed a strategy to secrete Listeriolysin O (LLO) toxin as a tool to escape the eukaryotic lysosomal system upon infection, allowing it to grow and proliferate unharmed inside the host cell.

Results

As a “proof of concept”, we present here the use of purified His-LLO H311A mutant protein and its conjugation on the surface of gold nanoparticles to promote the lysosomal escape of 40 nm-sized nanoparticles in mouse embryonic fibroblasts. Surface immobilization of LLO was achieved after specific functionalization of the nanoparticles with nitrile acetic acid, enabling the specific binding of histidine-tagged proteins.

Conclusions

Endosomal acidification leads to release of the LLO protein from the nanoparticle surface and its self-assembly into a 300 Å pore that perforates the endosomal/lysosomal membrane, enabling the escape of nanoparticles.
Feminisation of the health workforce and wage conditions of health professions: an exploratory analysis
Authors: Shannon Geordan , Minckas Nicole , Tan Des , Haghparast-Bidgoli Hassan , Batura Neha , Mannell Jenevieve
Published: October 2019

Background

The feminisation of the global health workforce presents a unique challenge for human resource policy and health sector reform which requires an explicit gender focus. Relatively little is known about changes in the gender composition of the health workforce and its impact on drivers of global health workforce dynamics such as wage conditions. In this article, we use a gender analysis to explore if the feminisation of the global health workforce leads to a deterioration of wage conditions in health.

Methods

We performed an exploratory, time series analysis of gender disaggregated WageIndicator data. We explored global gender trends, wage gaps and wage conditions over time in selected health occupations. We analysed a sample of 25 countries over 9 years between 2006 and 2014, containing data from 970,894 individuals, with 79,633 participants working in health occupations (48,282 of which reported wage data). We reported by year, country income level and health occupation grouping.

Results

The health workforce is feminising, particularly in lower- and upper-middle-income countries. This was associated with a wage gap for women of 26 to 36% less than men, which increased over time. In lower- and upper-middle-income countries, an increasing proportion of women in the health workforce was associated with an increasing gender wage gap and decreasing wage conditions. The gender wage gap was pronounced in both clinical and allied health professions and over lower-middle-, upper-middle- and high-income countries, although the largest gender wage gaps were seen in allied healthcare occupations in lower-middle-income countries.

Conclusion

These results, if a true reflection of the global health workforce, have significant implications for health policy and planning and highlight tensions between current, purely economic, framing of health workforce dynamics and the need for more extensive gender analysis. They also highlight the value of a more nuanced approach to health workforce planning that is gender sensitive, specific to countries’ levels of development, and considers specific health occupations.
Understanding and use of food labeling systems among Whites and Latinos in the United States and among Mexicans: Results from the International Food Policy Study, 2017
Authors: Nieto Claudia , Jáuregui Alejandra , Contreras-Manzano Alejandra , Arillo-Santillan Edna , Barquera Simón , White Christine M. , Hammond David , Thrasher James F.
Published: October 2019

Background

Obesity and chronic diseases could be prevented through improved diet. Most governments require at least one type of food labeling system on packaged foods to communicate nutrition information and promote healthy eating. This study evaluated adult consumer understanding and use of nutrition labeling systems in the US and Mexico, the most obese countries in the world.

Methods

Adults from online consumer panels in the US (Whites n = 2959; Latinos n = 667) and in Mexico (n = 3533) were shown five food labeling systems: 1. Nutrition Facts Table (NFT) that shows nutrients of concern per serving; 2. Guideline Daily Amounts (GDA) that shows levels of nutrients of concern; 3. Multiple Traffic-Light (MTL) that color codes each GDA nutrient (green = healthy; yellow = moderately unhealthy; red = unhealthy); 4. Health Star Rating System (HSR) that rates foods on a single dimension of healthiness; 5. Warning Label (WL) with a stop sign for nutrients present in unhealthy levels. Participants rated each label on understanding (“easy”/“very easy to understand” vs “difficult”/“very difficult to understand”), and, for NFTs and GDAs, frequency of use (“sometimes”/“often” vs “never”). Mixed logistic models regressed understanding and frequency of use on indicators of labeling systems (NFT = ref), testing for interactions by ethnicity (US Latinos, US Whites, Mexicans), while controlling for sociodemographic and obesity-related factors.

Results

Compared to the NFT, participants reported greater understanding of the WL (OR = 4.8; 95% CI = 4.4–5.3) and lower understanding of the HSR (OR = 0.34, 95% CI = 0.31–0.37) and the MTL (OR = 0.56, 95% CI = 0.52–0.61), with similar patterns across ethnic subgroups. Participants used GDAs less often than NFTs (OR = 0.48; 95%CI = 0.41–0.55), with the greatest difference among US Whites (OR = 0.10; 95%CI = 0.07–0.14).

Conclusions

Understanding and use of the GDA was similar to that of the NFT. Whites, Latinos, and Mexicans consistently reported the best understanding for WLs, a FOPL that highlights unhealthfulness of a product. Therefore, a FOPL summary indicator, such as WLs, may be more effective in both the US and Mexico for guiding consumers towards informed food choices.
Antibiotic prescriptions in Italian hospitalised children after serial point prevalence surveys (or pointless prevalence surveys): has anything actually changed over the years?
Authors: Tersigni Chiara , Montagnani Carlotta , D’Argenio Patrizia , Duse Marzia , Esposito Susanna , Hsia Yingfen , Sharland Mike , Galli Luisa
Published: October 2019

Background

Point prevalence surveys have been used in several studies to provide immediate and easily comparable information about antibiotic use and showed that about one third of hospitalised children had on ongoing antimicrobial prescription during their hospital admission. The aim of this study, as part of the Global Antimicrobial Resistance, Prescribing and Efficacy in Neonates and Children project, is to describe antimicrobial prescriptions among hospitalised children in four tertiary care hospitals in Italy to show if something has changed over the years.

Methods

Four tertiary care Italian’s hospitals joined three Point Prevalence Surveys (PPSs) in three different period of the year. All children under 18 years of age with an ongoing antimicrobial prescription, admitted on the participating wards at 8 o’clock in the morning of the selecting day were enrolled.

Results

A total of 1412 patients (475 neonates and 937 children) were admitted in the days of three PPSs. Overall, among the total admitted patients, 565 patients (40%) had an ongoing antimicrobial prescription in the days of the survey A total of 718 antibiotics were administered in the 485 admitted children and 133 in neonates. The most common indications for antibiotic therapy in children was Lower respiratory tract infections (244/718, 34%), while in neonates were prophylaxis for medical problems (35/133, 26.3%), newborn prophylaxis for newborn risk factors (29/133, 21.8%) and prophylaxis for surgical disease (15/133, 11.3%).

Conclusions

Based on our results, it appears that nothing has changed since the last PPS and that the quality improved targets, underlyined in previous studies, are always the same. Serial PPSs can be part of AMS strategies but they are not sufficient alone to produce changes in clinical practice.
Metastatic behavior and overall survival according to breast cancer subtypes in stage IV inflammatory breast cancer
Authors: van Uden D. J. P. , van Maaren M. C. , Strobbe L. J. A. , Bult P. , van der Hoeven J. J. , Siesling S. , de Wilt J. H. W. , Blanken-Peeters C. F. J. M.
Published: October 2019

Background

Distant metastatic disease is frequently observed in inflammatory breast cancer (IBC), with a poor prognosis as a consequence. The aim of this study was to analyze the association of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) based breast cancer subtypes in stage IV inflammatory breast cancer (IBC) with preferential site of distant metastases and overall survival (OS).

Methods

For patients with stage IV IBC, diagnosed in the Netherlands between 2005 and 2016, tumors were classified into four breast cancer subtypes: HR+/HER2−, HR+/HER2+, HR−/HER2+, and HR−/HER2−. Patient, tumor, and treatment characteristics and sites of metastases were compared. OS of the subtypes was compared using Kaplan-Meier curves and the log-rank test. Association between subtype and OS was assessed in multivariable models using logistic regression.

Results

In total, 744 eligible patients were included: 340 (45.7%) tumors were HR+/HER2−, 148 (19.9%) HR−/HER2+, 131 (17.6%) HR+/HER2+, and 125 (16.8%) HR−/HER2−. Bone was the most common metastatic site in all subtypes. A significant predominance of bone metastases was found in HR+/HER2− IBC (71.5%), and liver and lung metastases in the HR−/HER2+ (41.2%) and HR−/HER2− (40.8%) subtypes, respectively. In multivariable analysis, the HR−/HER2− subtype was associated with significantly worse OS as compared to the other subtypes.

Conclusion

Breast cancer subtypes in stage IV IBC are associated with distinct patterns of metastatic spread and display notable differences in OS. The use of breast cancer subtypes can guide a more patient-tailored staging directed to metastatic site and extend of disease.