bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing and fabricating a novel medical insole with universal fluid layer with auto-customizability
Authors: Shakouri Ehsan , Mossayebi Alireza , Manafi Babak
Published: May 2020

Medical insoles play a significant role in pressure reduction, proper stress–strain distribution, and correcting some deformities in the foot. The aim of the present research is to design and fabricate new medical insoles with universal fluid layer. After fabricating two types of insoles including flat silicone insole with shore 17 and flat silicone insole with universal fluid layer (medical silicone with shore 17 and silicone gel with shore 0), PEDAR test using one person in two standing and walking positions in three conditions comprised without the use of medical insole, using of flat medical silicone insole, and flat silicone insole with universal fluid layer was performed. These insoles were also modeled and solved in Abacus software according to the results obtained from mechanical properties testing of silicone and PEDAR test. The results of the finite element analysis showed that absorption of stress and strain in the static state by the silicone insoles with universal fluid layer was 63% and 63%, and in the dynamic state was 84% and 89% more than those obtained by the flat silicone insoles, respectively. The experimental results of the PEDAR system also showed that in the standing state, the silicone insoles with universal fluid layer and the flat silicone insoles had 58% and 30% pressure reduction, respectively, in comparison with without insole condition. Also, in the gait state, the silicone insoles with fluid layer and the flat silicone insole showed 37% and 9% pressure reduction, respectively, in comparison with without insole condition. Eventually, it was found out that the silicone insoles with fluid layer reduce plantar pressure well in comparison to the flat silicone insoles.
Validation of MicroRNA-188-5p Inhibition Power on Tumor Cell Proliferation in Papillary Thyroid Carcinoma
Authors: Zhou Ping , Irving Andrew , Wu Huifang , Luo Juan , Aguirre Johana , Costa Mariana , Khamsuree Monny , Gerads Natascha , Liu Weibang
Published: May 2020

Given the crucial role of microRNAs in the cellular proliferation of various types of cancers, we aimed to analyze the expression and function of a cellular proliferation-associated miR-188-5p in papillary thyroid carcinoma (PTC). Here we demonstrate that miR-188-5p is downregulated in PTC tumor tissues compared with the associated noncancerous tissues. We also validate that the miR-188-5p overexpression suppressed the PTC cancer cell proliferation. In addition, fibroblast growth factor 5 (FGF5) is observed to be downregulated in the PTC tumor tissues compared with the associated noncancerous tissues. Subsequently, FGF5 is identified as the direct functional target of miR-188-5p. Moreover, the silencing of FGF5 was found to inhibit PTC cell proliferation, which is the same pattern as miR-188-5p overexpression. These results suggest that miR-188-5p-associated silencing of FGF5 inhibits tumor cell proliferation in PTC. It also highlights the importance of further evaluating miR-188-5p as a potential biomarker and therapy target in PTC.
RNA Sequencing of Human Peripheral Nerve in Response to Injury: Distinctive Analysis of the Nerve Repair Pathways
Authors: Welleford Andrew S. , Quintero Jorge E. , Seblani Nader El , Blalock Eric , Gunewardena Sumedha , Shapiro Steven M. , Riordan Sean M. , Huettl Peter , Guduru Zain , Stanford John A. , van Horne Craig G. , Gerhardt Greg A.
Published: May 2020

The development of regenerative therapies for central nervous system diseases can likely benefit from an understanding of the peripheral nervous system repair process, particularly in identifying potential gene pathways involved in human nerve repair. This study employed RNA sequencing (RNA-seq) technology to analyze the whole transcriptome profile of the human peripheral nerve in response to an injury. The distal sural nerve was exposed, completely transected, and a 1 to 2 cm section of nerve fascicles was collected for RNA-seq from six participants with Parkinson’s disease, ranging in age between 53 and 70 yr. Two weeks after the initial injury, another section of the nerve fascicles of the distal and pre-degenerated stump of the nerve was dissected and processed for RNA-seq studies. An initial analysis between the pre-lesion status and the postinjury gene expression revealed 3,641 genes that were significantly differentially expressed. In addition, the results support a clear transdifferentiation process that occurred by the end of the 2-wk postinjury. Gene ontology (GO) and hierarchical clustering were used to identify the major signaling pathways affected by the injury. In contrast to previous nonclinical studies, important changes were observed in molecular pathways related to antiapoptotic signaling, neurotrophic factor processes, cell motility, and immune cell chemotactic signaling. The results of our current study provide new insights regarding the essential interactions of different molecular pathways that drive neuronal repair and axonal regeneration in humans.
A six-step brief intervention to reduce distress and increase treatment readiness in problem gamblers
Authors: Oakes Jane E , Manning Victoria , Rodda Simone N , Lubman Dan I
Published: May 2020

Objective:

The majority of people with gambling problems contact helplines when they are in crisis, hampering their capacity to explore suitable treatment options. To date, there has been limited research identifying the best way to support individuals to reduce distress and maximise further treatment-seeking. In this paper, we describe the development and piloting of the resulting six-step brief intervention.

Method:

A six-step brief intervention was developed based on a literature review of existing interventions for crisis management, semi-structured interviews with 19 participants comprising gambling and crisis support counsellors and consumers, as well as experts in the addiction field.

Results:

The resulting six-step brief-intervention focusses on (1) acknowledging and measuring distress; (2) normalising and reducing distress; (3) optimising motivation for change; (4) providing a sense of hope; (5) re-measuring distress and, if reduced; (6) exploring options for treatment and support.

Conclusion:

Whilst developed primarily for helpline counsellors, the intervention has potential application for health practitioners working across telephone, online and face-to-face services. Further research is required to determine its effectiveness in improving treatment engagement amongst people with gambling problems.
Predicting Police Officer Seat Belt Use: Evidence-Based Solutions to Improve Officer Driving Safety
Authors: Wolfe Scott , Lawson Spencer G. , Rojek Jeff , Alpert Geoffrey
Published: May 2020

One of the hidden dangers of police work is self-imposed—the failure to wear seat belts. Unfortunately, little evidence exists concerning the factors that account for why officers do not wear their seat belts. This study used a sample of 450 police officers to develop and test a framework for understanding the predictors of seat belt use. We found several factors that were associated with the frequency of officer seat belt use: the perceived likelihood of supervisors enforcing seat belt and other driving policies, organizational justice, having a departmental colleague previously struck by a vehicle, law enforcement experience, risky driving attitudes, number of prior on-duty collisions, being a patrol officer versus supervisor, and perceived risk of being involved in a vehicle collision. We discuss the practical implications of these findings as they apply to efforts aimed at improving officer driving safety and subsequent reduction in related injuries and deaths.
Rapid response to systemic steroid in macular alexandrite laser exposure: Multimodal imaging
Authors: Balikoglu-Yilmaz Melike , Kaya Mahmut , Erbezci Murat , Kaynak Suleyman
Published: May 2020

Purpose

To report the management of accidental macular photocoagulation during a 750-nm Alexandrite laser hair removal procedure.

Methods

Single case report with images.

Results

A 23-year-old girl presented with an immediate visual field defect in her right eye after direct inadvertent exposure to a single discharge from a 750-nm Alexandrite laser used for laser hair removal. Baseline Snellen visual acuity was 20/20 in the involved right eye but the patient reported a subjective visual field defect. She was treated with oral methylprednisolone that was started at a dose of 1 mg/kg/day and then gradually reduced. Six months after the initial exposure, the final visual acuity was 20/20 and there was a significant improvement in the macular lesion. However, the subjective visual field defect continued. She underwent multimodal retinal imaging with optical coherence tomography, fundus fluorescence angiography, and optical coherence tomography angiography in addition to a visual field test and microperimety.

Conclusion

The present case documents a gradual visual and anatomical improvement following macular photic damage after accidental occupational exposure to a 750-nm Alexandrite laser. The treatment should be arranged according to the localization of the laser damage. Optical coherence tomography angiography also has the potential to help noninvasively detect choriocapillaris damage.
Comparison of dynamic arterial and venous pressure between metal needles and plastic cannulas in incident hemodialysis patients with arteriovenous graft
Authors: Choi Sun Ryoung , Park Pyoungju , Han Sohee , Kim Cheolsu , Joo Narae , Kim Jwa Kyung , Song Young Rim , Kim Hyung Jik , Kim Sung Gyun , Lee Hyung Seok
Published: May 2020

Background and objects:

We hypothesized that plastic cannulae with 17-gauge inner needle compared to 16-gauge metal needles can have stable dynamic venous and arterial pressure maintaining prescribed blood flow safely during a hemodialysis treatment.

Design, setting, participants, and measurements:

A single-center, prospective, randomized, open-label clinical trial was conducted involving 16 incident hemodialysis patients who had arteriovenous graft placed as their first arteriovenous access. Subjects were randomized to metal needle group (n = 8) versus plastic cannula group (n = 8). We measured serial dynamic pre-pump arterial and venous pressure under five different blood pump flow rates (150, 200, 250, 300, and 350 mL/min).

Results:

The mean age of patients was 67.6 ± 8.5 (range: 51–81) years, and six patients (37.5%) were male. Patients with plastic cannula showed less negative arterial pre-pump pressures and lower venous pressures than those with metal needles at all prescribed blood flow rates, and the difference was statistically significant (P < 0.001).

Conclusion:

The plastic cannula had more stable arterial and venous pressures at prescribed blood pump flow rates than those pressures of the metal needle in incident patients with arteriovenous graft during hemodialysis.
Academics at play: Why the “publication game” is more than a metaphor
Authors: Butler Nick , Spoelstra Sverre
Published: May 2020

It is increasingly common to describe academic research as a “publication game,” a metaphor that connotes instrumental strategies for publishing in highly rated journals. However, we suggest that the use of this metaphor is problematic. In particular, the metaphor allows scholars to make a convenient, but ultimately misleading, distinction between figurative game-playing on one hand (i.e. pursuing external career goals through instrumental publishing) and proper research on the other hand (i.e. producing intrinsically meaningful research). In other words, the “publication game” implies that while academic researchers may behave just like players, they are not really playing a game. Drawing on semi-structured interviews, we show that this metaphor prevents us, ironically, from fully grasping the lusory attitude, or play-mentality, that characterizes academic work among critical management researchers. Ultimately, we seek to stimulate reflection about how our choice of metaphor can have performative effects in the university and influence our behavior in unforeseen and potentially undesirable ways.
Social media-enhanced learning in a small island developing states (SIDS) setting
Authors: Vaghjee Gounshali
Published: May 2020

The rapid and ongoing advances in technology are leading to significant transformations in the world, making it even more connected. The educational sector is also responding by developing new models to face and adopt these changes. Learners are exposed to new media technologies which have set the scene for more collaboration, participation and engagement in the learning environment. As research points towards an eagerness for the acceptance of social media in developing countries, there is a need to further explore its implication for education. In an era of globalization which creates more association among universities from developed nations and small island developing states (SIDS), the significance of investigating learners’ social media engagement level is even greater. This article documents the development of a Learner Social Media Engagement Level model for higher education institutions in SIDS based on a research in Mauritius. The analysis results in the identification of five main levels of participation, namely Curator, Consumer, Communicator, Collaborator and Producer. The article concludes with the social profile of each category of learner and highlights how the small state experience could be significant for a wider international community.
Mood work and political spaces: A consideration of the relationship between affect and political collectivity in grassroots urban activism
Authors: Mukherjee Jacob
Published: May 2020

This essay, based on a ‘militant ethnography’ of the small radical grassroots activist group Our London,1 outlines the importance of mood in developing political collectivity in oppositional politics. Applying Gilbert’s notion of affect as key to sociality, Highmore’s discussion of mood and mood work and Dean’s concept of affective infrastructure, I develop an account of Our London’s activities, and in particular its organisation of public events, that argues for the production of mood in political spaces as key to mobilising political collectivity. The significance of this work is in showing how oppositional political practices, as opposed to mere rhetoric or discourse, can develop forms of political collectivity and action; this is also a study of how forms of class politics can be performed and practised despite the difficulty of articulating such politics discursively – or even conceptualising society in class terms – in the context of a fragmented, neoliberal, post-Fordist city like London.
Doing data together – affective relations and mobile ethnography in home visits
Authors: Lydahl Doris , Holmberg Suvi , Günther Kirsi , Ranta Johanna
Published: May 2020

This article is concerned with the doing and production of data. We ask how data are made in intimate spaces such as the home in collaboration with the different parties involved in home-based care and services. The article builds on ethnographic field notes from 73 home visits, in the context of home-based mental health, substance abuse and social care for adults in Finland and Sweden. Drawing on affect theory, the article aims to foreground aspects of the production of data and research that are often edited out of the research process. In so doing, we argue that the production of data would not be possible without the active and affective collaboration of all parties involved in home visits. Thus, the article scrutinizes in detail the efforts made by different parties, such as researchers, clients and workers to do and produce data. While we study an atypical setting of institutional interaction, we contend that affects and affective relations gain particular importance in the home.
Perceived Managerial Competence of First-Line Nurse Managers: A Comparative Analysis Among Public Hospitals
Authors: Gunawan Joko , Aungsuroch Yupin , Fisher Mary L. , McDaniel Anna M. , Marzilli Colleen
Published: May 2020

Knowing the perceptions of first-line nurse managers (FLNMs) regarding their managerial competence is an important step to resolve disparities between their perceived competence and the competencies required for them to effectively function in their roles. Yet, evidence examining managerial competence of FLNMs among public hospitals in Indonesia is sparse. To fill this gap, we conducted a cross-sectional study aimed to identify managerial competence of FLNMs according to hospital type and ownership. This study was conducted from January to May 2018 and included a convenience sample of 233 FLNMs selected from 13 public hospitals. We used the Indonesian-First-Line Nurse Managers Managerial Competence Scale (I-FLNMMCS) to measure managerial competence. Descriptive statistics, Kruskal–Wallis, and Dunn’s Pairwise were used for data analysis. Findings showed a significant difference in managerial competence according to the hospital type ( p < .05). The FLNMs with a Diploma III, those relatively older, in their position for 7 or more years, and with managerial training in Type A hospitals (larger hospitals) had the highest managerial competence. The FLNMs with a bachelor’s degree, those relatively younger, with less training, and those in their position for 3 to 4 years in Type B and C hospitals (smaller hospitals) had less managerial competence. A significant difference was also found in managerial competence according to hospital ownership ( p <.05). Public hospitals owned by the Ministry of Health of Indonesia had the highest competence among the others. This study is useful for guiding future policy work for human resource development in public hospitals.
Localisation Across the Humanitarian-Development-Peace Nexus
Authors: Barakat Sultan , Milton Sansom
Published: May 2020

Whilst the relation between local and global levels has been a long-standing concern of humanitarian, development, and peace efforts, in recent years the term “localisation” has become a major issue in the humanitarian sector whilst peacebuilding scholarship has taken a “local turn.” This article analyses the concept of localisation across the three parts of the triple nexus—humanitarian, development, and peace. It traces the long-standing concern with the local in each of these domains, considering similarities and differences in their engagement with the local and counter-veiling trends towards universalisation, before proceeding to frame four challenges common to localisation across all forms of conflict response: defining the local, valuing local capacity, maintaining political will, and multi-scalar conflict response.
A Scenario-Based Methodology for Analyzing the Ethical, Legal, and Social Issues in Genomic Data Sharing
Authors: McWhirter Rebekah , Eckstein Lisa , Chalmers Don , Critchley Christine , Nielsen Jane , Otlowski Margaret , Nicol Dianne
Published: May 2020

Sharing of genomic and associated data is essential to clinical practice and biomedical research, and is increasingly encouraged by journals and funding bodies. Grappling with the range of legal and ethical issues raised by genomic data sharing presents a significant challenge, given the diversity of practices: from defined sharing of individual patient data, to broad-scale public sharing of research data, to uploading of direct-to-consumer test data by community members. Most commentary to date has discussed these issues in broad terms, but the debate can only progress if we engage with more granularity, grounded in jurisdictional and contextual specifics. We developed an empirical approach, creating a set of prototypical scenarios that capture the diversity of current genomic data sharing practices, which allows legal and ethical analysis of key issues at a granular level. The specificity of this approach provides a strong foundation for developing useful and relevant regulatory recommendations.
Garcinol Alone and in Combination With Cisplatin Affect Cellular Behavior and PI3K/AKT Protein Phosphorylation in Human Ovarian Cancer Cells
Authors: Zhang Jie , Fang Huan , Zhang Jinguo , Guan Wencai , Xu Guoxiong
Published: May 2020

Garcinol is a plant-derived compound that has some physiological benefits to human cells. However, the effect of garcinol on ovarian cancer (OC) cell proliferation and apoptosis is unknown. The current study aimed to examine the effects of garcinol alone and in combination with cisplatin (DDP) on cellular behavior and to explore the expression pattern of PI3K/AKT and nuclear factor-κB (NF-κB) in human OC cells. We found that OVCAR-3 cell viability was decreased after garcinol treatment. Garcinol alone and in combination with DDP significantly inhibited cell proliferation and had a synergistic effect evaluated by CompuSyn software. The cell cycle analysis showed the S phase arrest by garcinol. Furthermore, garcinol alone and in combination with DDP promoted cell apoptosis. The garcinol-induced apoptosis was further confirmed by the detection of cleavage forms of PARP and caspase 3. An increase in proapoptotic factor Bax expression was also found in garcinol-treated cells. Moreover, garcinol significantly decreased the phosphorylation of PI3K and AKT proteins and downregulated the expression of NF-κB. Thus, our data demonstrated that garcinol has the potential to be used as an anticancer agent and may synergize the effect of DDP. These actions are most likely through the regulation of the PI3K/AKT and NF-κB pathways.
Radiation Exposure–Induced Changes in the Immune Cells and Immune Factors of Mice With or Without Primary Lung Tumor
Authors: Pan Shuxian , Wang Jingjie , Wu Anqing , Guo Ziyang , Wang Ziyang , Zheng Lijun , Dai Yingchu , Zhu Lin , Nie Jing , Hei Tom K. , Zhou Guangming , Li Youchen , Li Bingyan , Hu Wentao
Published: May 2020

Recent studies have demonstrated that radiation activates in situ antitumor immunity and consequently induced a synergistic effect of radiotherapy and immunotherapy. However, studies related to radiation-induced changes in immune system of tumor-bearing mice are limited, which are of great significance to improve the efficacy of radioimmunotherapy. In this study, we first established a primary lung tumor mouse model using urethane. Then part of the right lung of the mouse was exposed to X-ray irradiation with a computed tomography–guided small animal irradiator and the changes of immune cells in both peripheral blood and spleen were determined by flow cytometry. Besides, the levels of both cytokines and immunoglobulins in mouse serum were detected by a protein chip. We found that B lymphocytes increased while CD8+T lymphocytes reduced significantly. Interleukin-3 (IL-3), IL-6, regulated upon activation, normally T-expressed, and presumably secreted factor (RANTES), and vascular endothelial growth factor (VEGF) were found to be decreased after tumor formation, and the similar results have also been observed with kappa, IgG3, IgE, IgM, and IgG2a. After irradiation, lower concentrations of IgD, kappa, and IgM were found in the serum. Our findings indicate that localized tumor irradiation caused some obvious changes like inhibiting the ability of innate immunity, and these changes may be useful in predicting prognosis.
Quantifying Biophoton Emissions From Human Cells Directly Exposed to Low-Dose Gamma Radiation
Authors: Cohen Jason , Vo Nguyen T. K. , Chettle David R. , McNeill Fiona E. , Seymour Colin B. , Mothersill Carmel E.
Published: May 2020

Biophoton emission leading to bystander effects (BEs) was shown in beta-irradiated cells; however, technical challenges precluded the analysis of the biophoton role in gamma-induced BEs. The present work was to design an experimental approach to determine if, what type, and how many biophotons could be produced in gamma-irradiated cells. Photon emission was measured in HCT116 p53+/+ cells irradiated with a total dose of 22 mGy from a cesium-137 source at a dose rate of 45 mGy/min. A single-photon detection unit was used and shielded with lead to reduce counts from stray gammas reaching the detector. Higher quantities of photon emissions were observed when the cells in a tissue culture vessel were present and being irradiated compared to a cell-free vessel. Photon emissions were captured at either 340 nm (in the ultraviolet A [UVA] range) or 610 nm. At the same cell density, radiation exposure time, and radiation dose, HCT116 p53+/+ cells emitted 2.5 times more UVA biophotons than 610-nm biophotons. For the first time, gamma radiation was shown to induce biophoton emissions from biological cells. As cellular emissions of UVA biophotons following beta radiation lead to BEs, the involvement of cellular emissions of the same type of UVA biophotons in gamma radiation-induced BEs is highly likely.
Intra-arterial neuroprotective therapy as an adjunct to endovascular intervention in acute ischemic stroke: A review of the literature and future directions
Authors: Link Thomas W , Santillan Alejandro , Patsalides Athos
Published: May 2020

Mechanical thrombectomy for acute ischemic stroke due to large vessel occlusion has been shown to significantly improve outcomes. However, despite efficient rates of recanalization (60–90%), the rates of functional independence remain suboptimal (14–58%), most likely due to pathways of cell death in the brain that have already committed despite successful reperfusion. Pharmacologic neuroprotection provides a potential means of preventing this inevitable damage through targeting excitotoxicity, reactive oxygen species, cellular apoptosis, and inflammation. Numerous clinical trials using various neuroprotective agents have failed, but the majority of these trials did not include endovascular reperfusion, and thus the drugs were not reaching the therapeutic target. Intra-arterial delivery of neuroprotective agents via the guide catheter already in place for mechanical thrombectomy could provide a way to deliver high doses directly to the affected territory while limiting systemic exposure. Agents that have shown promise via the intra-arterial route in preclinical as well as some clinical models include magnesium sulfate, verapamil, cold saline, stem cells, and various combined approaches. Targeted hypothermia, achieved with intra-carotid infusion of cold saline, may provide an effective means of achieving hypothermia of the ischemic tissue while avoiding the systemic effects that have limited its use previously. Combination therapy of targeted hypothermia and a cocktail of drugs that provide anti-excitotoxic, anti-oxidant, anti-apopototic, and anti-inflammatory effects may provide an ideal approach that deserves further study in clinical trials.
The role of MRI/TRUS fusion biopsy in the diagnosis of clinically significant prostate cancer
Authors: Benelli Andrea , Vaccaro Chiara , Guzzo Sonia , Nedbal Carlotta , Varca Virginia , Gregori Andrea
Published: May 2020

Background:

The aim of this work is to evaluate the detection rate of magnetic resonance imaging/transrectal ultrasound (MRI/TRUS) fusion-guided biopsy for clinically significant prostate cancers (Cs PCas), with particular interest in biopsy-naive patients and patients in active surveillance. MRI-targeted biopsy improves cancer detection rate (DR) in patients with prior negative biopsies; the current literature focuses on biopsy naive patients. We also evaluated the pathologic concordance between biopsies and surgical specimens.

Methods:

MRI/TRUS fusion-guided biopsies were performed between February 2016 and February 2019. Patients with previous negative biopsies, biopsy-naive or in active surveillance (AS) were included. Cs PCas were defined through Epstein’s criteria.

Results:

A total of 416 men were enrolled. The overall DRs and Cs PCa DRs were 49% and 34.3%, respectively. Cs PCas were 17.2%, 44.9% and 73.4%, respectively for PI-RADS 3, 4 or 5. Among biopsy-naive patients, 34.8% were found to have a Cs PCa, while a 43.6% tumour upgrading was achieved in men with a low risk of PCa. In patients who underwent radical prostatectomy (RP), the concordance between biopsy Gleason score (GS) (bGS) and pathological GS (pGS) was 90.8%.

Conclusion:

Our study highlights the role of MRI/TRUS fusion prostate biopsy in the detection of PCa in patients with previous negative biopsies focusing on Cs PCa diagnosis. The MRI/TRUS fusion biopsy is also emerging as a diagnostic tool in biopsy-naïve patients and deserves a fundamental role in AS protocols. A greater concordance between bGS and pGS can be achieved with targeted biopsies.
Large inoperable leiomyosarcoma of the prostate: treated by transcatheter arterial chemoembolization with drug-eluting microspheres
Authors: Wang Mao Qiang , Zhang Jin Long , Yuan Kai , Yuan Bing , Duan Feng , Yan Jie Yu , Wang Yan , Fu Jin Xin
Published: May 2020

Background:

Prostatic leiomyosarcoma (LMS) has a poor prognosis with a median overall survival (OS) of 15–18 months. For patients with metastatic disease, radical surgical resection, with or without adjuvant systemic chemotherapy and radiation therapy, unfortunately provides limited therapeutic benefit. Novel approaches for this lethal disease are urgently needed.

Objectives:

To evaluate the feasibility and efficacy of transarterial chemoembolization (TACE) with doxorubicin-eluting HepaSpheres (HS) for inoperable LMS of the prostate.

Methods:

This case series included 12 patients (median age 57 years, range 32–74) with inoperable LMS of the prostate who were treated with TACE using doxorubicin-eluting HS. All patients were pathologically proved by fine-needle biopsy. Symptomatic relief, complications, OS, and local disease control based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria were evaluated.

Results:

Symptomatic relief, including control of the gross hematuria, removal of indwelling catheters, improvement of constipation and perineal pain, were obtained in 100%, 75%, 100%, and 86%, respectively after TACE, without any major complications. At the last follow-up after TACE, the percentage of the tumor necrosis and volume reduction were present with a median value of 90% and 84%, respectively. TACE after two to four sessions allowed subsequent surgical resection in five (41.7%) patients. The median follow-up time was 29 months; the survival rate at 1, 2, and 3 years was 91.7%, 83.3%, and 41.7%, respectively, and the median OS was 29 months (range 9–49 months).

Conclusions:

TACE of inoperable LMS of the prostate appears to be safe and effective in providing tumor necrosis, shrinkage, and symptom relief; that could improve the quality of life and the survival rate of these patients.
Genetic aberrations and molecular biology of cardiac sarcoma
Authors: Urbini Milena , Astolfi Annalisa , Indio Valentina , Nannini Margherita , Pizzi Carmine , Paolisso Pasquale , Tarantino Giuseppe , Pantaleo Maria Abbondanza , Saponara Maristella
Published: May 2020

Cardiac tumors are rare and complex entities. Early assessment and differentiation between non-neoplastic and neoplastic masses, be they benign or malignant, is essential for guiding diagnosis, determining prognosis, and planning therapy. Cardiac sarcomas represent the most frequent primary malignant histotype. They could have manifold presentations so that the diagnosis is often belated. Moreover, considering their rarity and the limitation due to the cardiac location itself, the optimal multimodal management of patients affected by primary cardiac sarcomas still remains highly difficult and outcome dismal. Therefore, there is an urgent need to improve these results mainly focusing on more adequate tools for prompt diagnosis and exploring new and more effective therapies. Knowledge about the molecular landscape and pathogenesis of cardiac sarcoma is even more limited due to the rarity of this disease. In this sense, the molecular characterization of heart tumors could unfold potentially novel, druggable targets. In this review, we focused on genetic aberrations and molecular biology of cardiac sarcomas, collecting the scarce information available and resuming all the molecular findings discovered in each tumor subtype, with the aim to get further insights on mechanisms involved in tumor growth and to possibly highlight specific molecular profiles that can be used as diagnostic tests and unveil new clinically actionable targets in this tricky and challenging disease.
Immune checkpoint inhibitors in advanced or metastatic mucosal melanoma: a systematic review
Authors: Li Jiarui , Kan Haoxuan , Zhao Lin , Sun Zhao , Bai Chunmei
Published: May 2020

Background:

Conventional cytotoxic chemotherapy offers minor benefit to patients with mucosal melanoma (MM). Although immune checkpoint inhibitors (ICIs) have become the preferred approach in patients with advanced or metastatic cutaneous melanoma, the evidence of their clinical use for MM is still limited. This systematic review aims to summarize the efficacy and safety of ICIs in advanced or metastatic MM.

Methods:

We searched electronic databases, conference abstracts, clinical trial registers and reference lists for relevant studies. The primary outcomes included the overall response rate (ORR), median progression-free survival (PFS), median overall survival (OS), one-year PFS rate, and one-year OS rate.

Results:

This review identified 13 studies assessing anti-CTLA-4 monotherapy, 22 studies assessing anti-PD-1 monotherapy, two studies assessing anti-CTLA-4 and anti-PD-1 combination therapy, one study assessing anti-PD-1 antibodies combined with axitinib, and three studies assessing anti-PD-1 antibodies combined with radiotherapy. For most patients who received ipilimumab monotherapy, the ORR ranged from 0% to 17%, the median PFS was less than 5 months, and the median OS was less than 10 months. For patients who received nivolumab or pembrolizumab monotherapy, most studies showed an ORR of more than 15% and a median OS of more than 11 months. The combined administration of anti-CTLA-4 and anti-PD-1 agents showed benefits over single-agent therapy with an ORR of more than 33.3%. In a phase Ib trial of toripalimab in combination with axitinib, approximately half of patients had complete or partial responses. Three retrospective studies that investigated anti-PD-1 antibodies combined with radiotherapy showed an ORR of more than 50%, which was higher than each single modality treatment.

Conclusions:

Immune checkpoint inhibitors, especially anti-PD-1 monoclonal antibodies alone and in combination with anti-CTLA-4 monoclonal antibodies or other modalities, are promising treatment options for advanced or metastatic MM. However, high-level evidence is still needed to support the clinical application.
Cisplatin-induced renal toxicity in elderly people
Authors: Duan ZhiYu , Cai GuangYan , Li JiJun , Chen XiangMei
Published: May 2020

Despite available prevention and treatment measures, such as hydration, diuresis, magnesium supplementation, and amifostine, renal toxicity is still one of the major dose-limiting side effects of cisplatin. The aim of this review is to discuss the issue of cisplatin-induced nephrotoxicity in the elderly. Compared with young patients, the incidences of cisplatin-induced nephrotoxicity and acute kidney injury (AKI) in elderly patients are significantly increased, and survival time may be decreased. Following cisplatin treatment of elderly patients, tubulointerstitial injuries will be significantly aggravated based on their original age, both for acute injuries due to cell necrosis and exfoliation and chronic injuries due to interstitial fibrosis, tubular atrophy, and dilatation. The high incidence of cisplatin-induced nephrotoxicity in elderly patients may be associated with renal hypoperfusion; increased comorbidities, such as chronic kidney disease (CKD), cardiovascular disease, and diabetes mellitus; increased use of combined drugs [especially non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitor and angiotensin receptor blockers (ACEI/ARB), and antibiotics]; decreased clearance of cisplatin; and high plasma ultrafilterable cisplatin. Considering hemodynamic stability and water balance, short duration and low volume hydration may be more suitable for treating elderly people. With the increasing popularity of low-dose daily/weekly regimens, we do not recommend routine diuretic treatment for elderly patients. We recommend using a less nephrotoxic platinum if large doses of cisplatin (100mg/m2) are needed.
Rationale and protocol design for the TORG1835/NEXT-SHIP study: a phase II study of carboplatin, etoposide and nintedanib for unresectable limited/extensive disease small cell lung cancer with idiopathic pulmonary fibrosis
Authors: Ikeda Satoshi , Ogura Takashi , Kato Terufumi , Kenmotsu Hirotsugu , Iwasawa Tae , Misumi Toshihiro , Yamanaka Takeharu , Okamoto Hiroaki
Published: May 2020

Background:

Interstitial pneumonia (IP) is one of the most common and poor prognostic comorbidities in patients with small cell lung cancer (SCLC). The pharmacotherapy for SCLC occasionally induces fatal acute exacerbation of comorbid IP, especially in patients with idiopathic pulmonary fibrosis (IPF). Safe and effective pharmacotherapy is of greater importance in patients with SCLC and IPF, because SCLC presents a poor prognosis without systemic treatment. Nintedanib is expected to restrain acute exacerbation and present angiogenesis-inhibiting effects.

Methods:

The TORG1835/NEXT-SHIP study is the world’s first multi-center, single-arm, phase II trial for unresectable limited or extensive disease SCLC with IPF. The patients receive carboplatin (area under the curve 5, day 1), etoposide (<75 years old: 100 mg/m2; ⩾75 years old: 80 mg/m2; days 1–3), and nintedanib (150 mg twice a day) every 3 weeks for four cycles. After completion or discontinuation of carboplatin plus etoposide, the patients continue nintedanib until the discontinuation criteria are met. The primary endpoint is the incidence of acute exacerbation of IPF at 28 days after last administration of cytotoxic anti-cancer agents. We set an expected value of 5% and a threshold value of 20%. Taking statistical points (a/b errors: 0.05/0.75) and ineligible patients into account, the sample size was set at 33. The key secondary endpoints are time to first acute exacerbation of IPF, overall response rate, progression-free survival, overall survival, and toxicities.

Discussion:

Because there is no clinical trial for unresectable SCLC with IPF, our study would provide a major impact on clinical practice.

Trial registration:

Japan Registry of Clinical Trials, jRCTs031190119, registered date: October 18, 2019 – Retrospectively registered, https://jrct.niph.go.jp/en-latest-detail/jRCTs031190119
Examining Risk-Reduction Behavior Toward Water Quality Among Restaurant Guests
Authors: Cho Meehee , Bonn Mark A. , Li Jun (Justin)
Published: May 2020

Globally, there is a growing concern about health threats from water pollution and its effects upon products used in the restaurant food preparation process. Thus, the use of contaminated water for commercial food preparation represents a high source of risk for disease-causing illnesses upon human health in both developed and developing countries. Using the Protection Motivation Theory, a convenience sampling of n = 506 Chinese residents and visitors, defined as non-Chinese residents born and socialized in cultures outside of China, who dined in restaurants within a major Chinese metropolitan area, were used to determine how guests responded to perceived threats of consuming contaminated food products used for menu items tainted by impure tap water during the food and beverage preparation process. Perceived water quality concerns were found to manifest a fear appeal that initiated two protection motivation dimensions representing threat appraisal (severity and vulnerability) and coping appraisal (response-efficacy and self-efficacy), with severity and self-efficacy receiving the highest perceptual concerns. Results documented that when restaurant guests perceived a high level of self-efficacy, they were more likely to dine out regardless of perceived risks about unsafe restaurant water quality issues. All relationships involving threat and coping appraisal, and risk-reduction behavior toward dining out were significantly different between restaurant guests representing Chinese residents and non-Chinese residents. Findings revealed that threat appraisal upon risk-reduction behavior toward dining out were positively stronger for non-Chinese residents.
CD4+/CD8+ ratio positively correlates with coronary plaque instability in unstable angina pectoris patients but fails to predict major adverse cardiovascular events
Authors: Chai Dayang , Kong Xiangquan , Lu Shu , Zhang Junjie
Published: May 2020

Background:

The association between CD4+/CD8+ ratio and coronary plaque instability in patients with unstable angina pectoris (UAP) has not been investigated. We sought to elucidate the correlation between CD4+/CD8+ ratio and plaque instability in this patient population.

Methods:

We enrolled 266 UAP patients who underwent pre-intervention optical coherence tomography (OCT) examination and percutaneous coronary intervention in our center from January 2016 to January 2018. Features of coronary plaques in the culprit arteries were classified as unstable plaque and stable plaque. Primary endpoint was occurrence of a major adverse cardiovascular event (MACE). Receiver operating characteristic (ROC) analyses were used to determine the predictive efficacy of the CD4+/CD8+ ratio for a group of unstable plaque patients, and binary logistic regression analysis was performed to evaluate potential independent predictors of plaque instability. All-cause mortality and MACE between the two groups were analyzed.

Results:

UAP patients with unstable plaque had a higher CD4/CD8 ratio compared with stable plaque patients ( p < 0.05). Results of binary logistic regression analyses showed that CD4+/CD8+ ratio ⩾1.725 and prior stroke were predictors and risk factors of plaque instability ( p < 0.05). ROC analyses showed that CD4+/CD8+ ratio ⩾1.725 was predictive of plaque instability in UAP patients. However, the Kaplan–Meier estimate for MACE and all-cause mortality showed no statistical significance.

Conclusions:

Higher CD4+/CD8+ ratio is associated with higher risk of plaque instability in our cohort of UAP patients. However, CD4+/CD8+ ratio was not an independent predictor of 1-year MACE or all-cause mortality.
The anti-angiogenic tyrosine kinase inhibitor Pazopanib kills cancer cells and disrupts endothelial networks in biomimetic three-dimensional renal tumouroids
Authors: Stamati Katerina , Redondo Patricia A , Nyga Agata , Neves Joana B , Tran Maxine GB , Emberton Mark , Cheema Umber , Loizidou Marilena
Published: May 2020

Pazopanib is a tyrosine kinase inhibitor used to treat renal cell carcinoma. Few in vitro studies investigate its effects towards cancer cells or endothelial cells in the presence of cancer. We tested the effect of Pazopanib on renal cell carcinoma cells (CAKI-2,786-O) in two-dimensional and three-dimensional tumouroids made of dense extracellular matrix, treated in normoxia and hypoxia. Finally, we engineered complex tumouroids with a stromal compartment containing fibroblasts and endothelial cells. Simple CAKI-2 tumouroids were more resistant to Pazopanib than 786-O tumouroids. Under hypoxia, while the more ‘resistant’ CAKI-2 tumouroids showed no decrease in viability, 786-O tumouroids required higher Pazopanib concentrations to induce cell death. In complex tumouroids, Pazopanib exposure led to a reduction in the overall cell viability (p < 0.0001), disruption of endothelial networks and direct killing of renal cell carcinoma cells. We report a biomimetic multicellular tumouroid for drug testing, suitable for agents whose primary target is not confined to cancer cells.
Levothyroxine prescriptions trends may indicate a downtrend in prescribing
Authors: Jonklaas Jacqueline , DeSale Sameer
Published: May 2020

Background:

There has been a trend for increased prescribing of levothyroxine (LT4) in many countries, including the United States. Several different factors have been suggested to be the cause of this practice pattern. These factors include increased size of the United States population, more diagnosis of hypothyroidism, more treatment of minimally elevated thyroid-stimulating hormone (TSH) levels, more use of LT4 in older patients, and use of LT4 for treatment of euthyroid patients with non-thyroidal conditions.

Methods:

The electronic databases of the MedStar Health system operating in the Washington, DC and Maryland areas were interrogated to determine the number of patients who were being prescribed levothyroxine during the time period 2008–2016, the number of prescriptions supplied to these individuals, the associated diagnosis, and whether the prescriptions were new or existing prescriptions. Regression analyses were also performed to determine the prescribing trends during this time period.

Results:

Although the annual number of levothyroxine prescriptions increased during this time period, the percentage of patients in the database receiving levothyroxine for hypothyroidism initially increased and then decreased over time (2.5% to 3.2% to 2.5%). The percentage of prescriptions written for patients who did not appear to carry a diagnosis of hypothyroidism steadily declined (3.5% to 1.0%). Although the percentage of patients with existing prescriptions for hypothyroidism initially increased and then were maintained at steady levels (1.4% to 2.4% to 2.2%), a smaller percentage of patients with existing prescriptions were documented over time when there was no diagnosis of hypothyroidism (1.45% to 0.89%). The percentage of patients with new prescriptions declined over time for all groups. The number of annual 90-day period prescriptions increased over the time for patients with a diagnosis of hypothyroidism, but down-trended starting over the latter part of the time period for those patients without a diagnosis of hypothyroidism.

Conclusion:

Taken together, these data suggest that there may be a stabilization, and even a down-trend in levothyroxine prescribing with the MedStar system. The decrease in levothyroxine prescribing appears to be accounted for by less use of levothyroxine without an established diagnosis of hypothyroidism, and less initiation of new prescriptions.