bluuebunny/crossref_metadata_2025_split huggingface dataset:
A health care labyrinth: perspectives of caregivers on the journey to accessing timely cancer diagnosis and treatment for children in India
Authors: Faruqui Neha , Joshi Rohina , Martiniuk Alexandra , Lowe Jennifer , Arora Ramandeep , Anis Huma , Kalra Manas , Bakhshi Sameer , Mishra Ananya , Santa Ayyagari , Sinha Sudha , Siddaiahgari Sirisharani , Seth Rachna , Bernays Sarah 
Published: December 2019

AbstractBackgroundCure rates for children with cancer in India lag behind that of high-income countries. Various disease, treatment and socio-economic related factors contribute to this gap including barriers in timely access of diagnostic and therapeutic care. This study investigated barriers to accessing care from symptom onset to beginning of treatment, from perspectives of caregivers of children with cancer in India.MethodsSemi-structured in-depth interviews were conducted with caregivers of children (< 18 years) diagnosed with cancer in seven tertiary care hospitals across New Delhi and Hyderabad. Purposive sampling to saturation was used to ensure adequate representation of the child’s gender, age, cancer type, geographical location and socioeconomic status. Interviews were audio recorded after obtaining informed consent. Thematic content analysis was conducted and organised using NVivo 11.ResultsThirty-nine caregivers were interviewed, where three key themes emerged from the narratives: time intervals to definitive diagnosis and treatment, the importance of social supportive care and the overall accumulative impacts of the journey. There were two phases encapsulating the experiences of the family: referral pathways taken to reach the hospital and after reaching the hospital. Most caregivers, especially those from distant geographical areas had variable and inconsistent referral pathways partly due to poor availability of specialist doctors and diagnostic facilities outside major cities, influence from family or friends, and long travel times. Upon reaching the hospital, families mostly from public hospitals faced challenges navigating the hospital facilities, finding accommodation, and comprehending the diagnosis and treatment pathway. Throughout both phases, financial constraint was a recurring issue amongst low-income families. The caregiver’s knowledge and awareness of the disease and health system, religious and social factors were also common barriers.ConclusionThis qualitative study highlights and explores some of the barriers to childhood cancer care in India. Our findings show that referral pathways are intrinsically linked to the treatment experience and there should be better recognition of the financial and emotional challenges faced by the family that occur prior to definitive diagnosis and treatment. This information would help inform various stakeholders and contribute to improved interventions addressing these barriers.
Indwelling pleural catheters for malignancy-associated pleural effusion: report on a single centre’s ten years of experience
Authors: Frost Nikolaj , Brünger Martin , Ruwwe-Glösenkamp Christoph , Raspe Matthias , Tessmer Antje , Temmesfeld-Wollbrück Bettina , Schürmann Dirk , Suttorp Norbert , Witzenrath Martin 
Published: December 2019

AbstractIntroductionRecurrent pleural effusion is a common cause of dyspnoea, cough and chest pain during the course of malignant diseases. Chemical pleurodesis had been the only definitive treatment option until two decades ago. Indwelling pleural catheters (IPC) emerged as an alternative, not only assuring immediate symptom relief but also potentially leading to pleurodesis in the absence of sclerosing agents.MethodsIn this single-centre retrospective observational study patient characteristics, procedural variables and outcome in a large population of patients with IPC in malignancy were evaluated and prognostic factors for pleurodesis were identified.ResultsFrom 2006 to 2016, 395 patients received 448 IPC, of whom 121 (30.6%) had ovarian, 91 (23.0%) lung and 45 (11.4%) breast cancer. The median length of IPC remaining in place was 1.2 months (IQR, 0.5–2.6), the median survival time after insertion 2.0 months (IQR, 0.6–6.4). An adequate symptom relief was achieved in 94.9% of all patients, with no need for subsequent interventions until last visit or death. In patients surviving ≥30 days after IPC insertion, pleurodesis was observed in 44.5% and was more common in patients < 60 years (HR, 1.72; 95% CI, 1.05–2.78;p = 0.03). The use of an additional talc slurry via the IPC was highly predictive for pleurodesis (HR 6.68; 95% CI, 1.44–31.08;p = 0.02). Complications occurred in 13.4% of all procedures (n = 60), 41.8% concerning infections (local infections at the tunnel/exit site (n = 14) and empyema (n = 11)), and 98.3% being low or mild grade (n = 59). Complication rates were higher in men than women (18.6 vs. 12.4%,p = 0.023).ConclusionHigh efficacy in symptom relief and a favourable safety profile confirm IPC as suitable first line option in most malignant pleural effusions. The study presents the largest dataset on IPC in gynaecologic cancer to date. Gender-specific differences in complication rates warrant further study.
Dual consent? Donors’ and recipients’ views about involvement in decision-making on the use of embryos created by gamete donation in research
Authors: Baía I. , de Freitas C. , Samorinha C. , Provoost V. , Silva S. 
Published: December 2019

Abstract
Background
Reasonable disagreement about the role awarded to gamete donors in decision-making on the use of embryos created by gamete donation (EGDs) for research purposes emphasises the importance of considering the implementation of participatory, adaptive, and trustworthy policies and guidelines for consent procedures. However, the perspectives of gamete donors and recipients about decision-making regarding research with EGDs are still under-researched, which precludes the development of policies and guidelines informed by evidence. This study seeks to explore the views of donors and recipients about who should take part in consent processes for the use of EGDs in research.

Methods
From July 2017 to June 2018, 72 gamete donors and 175 recipients completed a self-report structured questionnaire at the Portuguese Public Bank of Gametes (response rate: 76%). Agreement with dual consent was defined as the belief that the use of EGDs in research should be consented by both donors and recipients.

Results
The majority of participants (74.6% of donors and 65.7% of recipients) were willing to donate embryos for research. Almost half of the donors (48.6%) and half of the recipients (46.9%) considered that a dual consent procedure is desirable. This view was more frequent among employed recipients (49.7%) than among non-employed (21.4%). Donors were less likely to believe that only recipients should be involved in giving consent for the use of EGDs in research (25.0% vs. 41.7% among recipients) and were more frequently favourable to the idea of exclusive donors’ consent (26.4% vs. 11.4% among recipients).

Conclusions
Divergent views on dual consent among donors and recipients indicate the need to develop evidence-based and ethically sustainable policies and guidelines to protect well-being, autonomy and reproductive rights of both stakeholder groups. More empirical research and further theoretical normative analyses are needed to inform people-centred policy and guidelines for shared decision-making concerning the use of EGDs for research.
DPF is a cell-density sensing factor, with cell-autonomous and non-autonomous functions during Dictyostelium growth and development
Authors: Meena Netra Pal , Jaiswal Pundrik , Chang Fu-Sheng , Brzostowski Joseph , Kimmel Alan R. 
Published: December 2019

AbstractBackgroundCellular functions can be regulated by cell-cell interactions that are influenced by extra-cellular, density-dependent signaling factors.Dictyosteliumgrow as individual cells in nutrient-rich sources, but, as nutrients become depleted, they initiate a multi-cell developmental program that is dependent upon a cell-density threshold. We hypothesized that novel secreted proteins may serve as density-sensing factors to promote multi-cell developmental fate decisions at a specific cell-density threshold, and useDictyosteliumin the identification of such a factor.ResultsWe show that multi-cell developmental aggregation inDictyosteliumis lost upon minimal (2-fold) reduction in local cell density. Remarkably, developmental aggregation response at non-permissive cell densities is rescued by addition of conditioned media from high-density, developmentally competent cells. Using rescued aggregation of low-density cells as an assay, we purified a single, 150-kDa extra-cellular protein with density aggregation activity. MS/MS peptide sequence analysis identified the gene sequence, and cells that overexpress the full-length protein accumulate higher levels of a development promoting factor (DPF) activity than parental cells, allowing cells to aggregate at lower cell densities; cells deficient for thisDPFgene lack density-dependent developmental aggregation activity and require higher cell density for cell aggregation compared to WT. Density aggregation activity co-purifies with tagged versions of DPF and tag-affinity-purified DPF possesses density aggregation activity. In mixed development with WT, cells that overexpress DPF preferentially localize at centers for multi-cell aggregation and define cell-fate choice during cytodifferentiation. Finally, we show that DPF is synthesized as a larger precursor, single-pass transmembrane protein, with the p150 fragment released by proteolytic cleavage and ectodomain shedding. The TM/cytoplasmic domain of DPF possesses cell-autonomous activity for cell-substratum adhesion and for cellular growth.ConclusionsWe have purified a novel secreted protein, DPF, that acts as a density-sensing factor for development and functions to define local collective thresholds forDictyosteliumdevelopment and to facilitate cell-cell communication and multi-cell formation. Regions of high DPF expression are enriched at centers for cell-cell signal-response, multi-cell formation, and cell-fate determination. Additionally, DPF has separate cell-autonomous functions for regulation of cellular adhesion and growth.
Clinicopathologic features of remnant gastric cancer after curative distal gastrectomy according to previous reconstruction method: a retrospective cohort study
Authors: Park Yong-Eun , Kim Sang-Woon 
Published: December 2019

Abstract
Background
Survival rate of patients treated for gastric cancer has increased due to early detection and improvements of surgical technique and chemotherapy. Increase in survival rate has led to an increase in the risk for remnant gastric cancer (RGC). The purpose of this study was to investigate clinicopathologic features of RGC according to previous reconstruction method and factors affecting the interval from previous curative distal gastrectomy for gastric cancer to RGC occurrence.

Methods
Medical records of patients diagnosed with RGC at Yeungnam University Medical Center from January 2000 to December 2017 who had a history of distal gastrectomy with D2 LN dissection due to gastric cancer were reviewed retrospectively.

Results
Forty-eight patients were enrolled in this study. The mean interval of 48 RGC patients was 105.6 months (8.8 years). RGC after Billroth II reconstruction recurred more often at anastomosis site than RGC after Billroth I reconstruction (p = 0.001). The mean interval of RGC after Billroth I reconstruction was 67 months, shorter than 119 months of RGC after Billroth II reconstruction (p = 0.003). On the contrary, interval showed no difference according to stage of previous gastric cancer, remnant gastric cancer, or sex (p = 0.810, 0.145, and 0.372, respectively).

Conclusions
RGC after Billroth I reconstruction tends to arise earlier at non-anastomosis site than RGC after Billroth II. Therefore, we should examine non-anastomosis site carefully from the beginning of surveillance after gastric cancer surgery with Billroth I reconstruction for better outcome.
Association of pre-surgery to pre-radiotherapy lymphocyte counts ratio with disease-free survival in rectal cancer patients receiving neoadjuvant concurrent chemoradiotherapy
Authors: Xu Hongen , You Guangxian , Zhang Minjun , Song Tao , Zhang Haibo , Yang Jia , Jia Yongshi , Tang Jianming , Liang Xiaodong 
Published: December 2019

Abstract
Background
Colorectal cancer is the fourth most common cancer globally and neoadjuvant concurrent chemoradiotherapy (nCRT) and surgery are the standard treatments for locally advanced colorectal carcinoma. This study investigated the association between dynamic changes in absolute lymphocyte counts (ALCs) and disease-free survival (DFS) in rectal cancer patients receiving nCRT and identified factors associated with these changes.

Methods
We retrospectively examined 34 patients with locally advanced rectal cancer who received nCRT followed by surgery and adjuvant chemotherapy. The association between ALCs and DFS and that between ALCs and downstaging were analyzed and potential clinical- and treatment-related factors related to dynamic changes in ALCs were subsequently evaluated. The patient eligibility criteria were as follows: pathologically confirmed rectal adenocarcinoma, clinical stages II–III, ≥ 18 years of age, and so on. Pre-RTL was defined as ALCs obtained before the initiation of nCRT and pre-SL was defined as ALCs obtained before surgery. We measured pre-SL to pre-RTL ratio (pre-SLR), DFS, and ALCs.

Results
The median ALC declined significantly during nCRT. A lower pre-SLR was associated with poorer DFS with statistical significance in Kaplan–Meier (p = 0.007), univariate regression (hazard ratio [HR] = 6.287, 95% confidence interval [CI] 1.374–28.781, p = 0.018), and multivariable regression (HR = 7.347, 95% CI 1.595–33.850, p = 0.011) analyses. Neither patient characteristics nor treatment-related factors were related to downstaging. The pelvic bone marrow (PBM) volume receiving at least 30 Gy (V30) was significantly associated with pre-SLR in the univariate (HR = 5.760, 95% CI 1.317–25.187, p = 0.020) and multivariable (HR = 5.760, 95% CI 1.317–25.187, p = 0.020) regression analyses.

Limitations
Our study had several limitations. The sample size was small and the study was performed in a selected population, which may limit the generalization of the findings.

Conclusions
Radiotherapy had a profound impact on the change in ALCs. A lower pre-SLR was significantly associated with poorer DFS in rectal cancer patients receiving nCRT. The V30 of PBM was a predictor of pre-SLR.
Individualized home-based exercise and nutrition interventions improve frailty in older adults: a randomized controlled trial
Authors: Hsieh Tsung-Jen , Su Shin-Chang , Chen Chun-Wei , Kang Yaw-Wen , Hu Ming-Hsia , Hsu Li-Lin , Wu Szu-Yun , Chen Likwang , Chang Hsing-Yi , Chuang Shao-Yuan , Pan Wen-Harn , Hsu Chih-Cheng 
Published: December 2019

Abstract
Background
Frail older adults are predisposed to multiple comorbidities and adverse events. Recent interventional studies have shown that frailty can be improved and managed. In this study, effective individualized home-based exercise and nutrition interventions were developed for reducing frailty in older adults.

Methods
This study was a four-arm, single-blind, randomized controlled trial conducted between October 2015 and June 2017 at Miaoli General Hospital in Taiwan. Overall, 319 pre-frail or frail older adults were randomly assigned into one of the four study groups (control, exercise, nutrition, and exercise plus nutrition [combination]) and followed up during a 3-month intervention period and 3-month self-maintenance period. Improvement in frailty scores was the primary outcome. Secondary outcomes included improvements in physical performance and mental health. The measurements were performed at baseline, 1 month, 3 months, and 6 months.

Results
At the 6-month measurement, the exercise (difference in frailty score change from baseline: − 0.23; 95% confidence interval [CI]: − 0.41, − 0.05; p = 0.012), nutrition (− 0.28; 95% CI: − 0.46, − 0.11; p = 0.002), and combination (− 0.34; 95% CI: − 0.52, − 0.16; p <  0.001) groups exhibited significantly greater improvements in the frailty scores than the control group. Significant improvements were also observed in several physical performance parameters in the exercise, nutrition, and combination groups, as well as in the 12-Item Short Form Health Survey mental component summary score for the nutrition group.

Conclusions
The designated home-based exercise and nutrition interventions can help pre-frail or frail older adults to improve their frailty score and physical performance.

Trial registration
Retrospectively registered at ClinicalTrials.gov (identifier: NCT03477097); registration date: March 26, 2018.
Apelin-13/APJ system attenuates early brain injury via suppression of endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation and oxidative stress in a AMPK-dependent manner after subarachnoid hemorrhage in rats
Authors: Xu Weilin , Li Tao , Gao Liansheng , Zheng Jingwei , Yan Jun , Zhang Jianmin , Shao Anwen 
Published: December 2019

Abstract
Background
Neuroinflammation and oxidative stress play important roles in early brain injury following subarachnoid hemorrhage (SAH). This study is the first to show that activation of apelin receptor (APJ) by apelin-13 could reduce endoplasmic reticulum (ER)-stress-associated inflammation and oxidative stress after SAH.

Methods
Apelin-13, apelin siRNA, APJ siRNA, and adenosine monophosphate-activated protein kinase (AMPK) inhibitor-dorsomorphin were used to investigate if the activation of APJ could provide neuroprotective effects after SAH. Brain water content, neurological functions, blood-brain barrier (BBB) integrity, and inflammatory molecules were evaluated at 24 h after SAH. Western blotting and immunofluorescence staining were applied to assess the expression of target proteins.

Results
The results showed that endogenous apelin, APJ, and p-AMPK levels were significantly increased and peaked in the brain 24 h after SAH. In addition, administration of exogenous apelin-13 significantly alleviated neurological functions, attenuated brain edema, preserved BBB integrity, and also improved long-term spatial learning and memory abilities after SAH. The underlying mechanism of the neuroprotective effects of apelin-13 is that it suppresses microglia activation, prevents ER stress from overactivation, and reduces the levels of thioredoxin-interacting protein (TXNIP), NOD-like receptor pyrin domain-containing 3 protein (NLRP3), Bip, cleaved caspase-1, IL-1β, TNFα, myeloperoxidase (MPO), and reactive oxygen species (ROS). Furthermore, the use of APJ siRNA and dorsomorphin abolished the neuroprotective effects of apelin-13 on neuroinflammation and oxidative stress.

Conclusions
Exogenous apelin-13 binding to APJ attenuates early brain injury by reducing ER stress-mediated oxidative stress and neuroinflammation, which is at least partly mediated by the AMPK/TXNIP/NLRP3 signaling pathway.
The phosphodiesterase 10 inhibitor papaverine exerts anti-inflammatory and neuroprotective effects via the PKA signaling pathway in neuroinflammation and Parkinson’s disease mouse models
Authors: Lee Yu-Young , Park Jin-Sun , Leem Yea-Hyun , Park Jung-Eun , Kim Do-Yeon , Choi Youn-Hee , Park Eun-Mi , Kang Jihee Lee , Kim Hee-Sun 
Published: December 2019

Abstract
Background
Neuroinflammation plays a pivotal role in the pathogenesis of Parkinson’s disease (PD). Thus, the development of agents that can control neuroinflammation has been suggested as a promising therapeutic strategy for PD. In the present study, we investigated whether the phosphodiesterase (PDE) 10 inhibitor has anti-inflammatory and neuroprotective effects in neuroinflammation and PD mouse models.

Methods
Papaverine (PAP) was utilized as a selective inhibitor of PDE10. The effects of PAP on the expression of pro-inflammatory molecules were examined in lipopolysaccharide (LPS)–stimulated BV2 microglial cells by ELISA, RT-PCR, and Western blot analysis. The effects of PAP on transcription factors were analyzed by the electrophoretic mobility shift assay, the reporter gene assay, and Western blot analysis. Microglial activation and the expression of proinflammatory molecules were measured in the LPS- or MPTP-injected mouse brains by immunohistochemistry and RT-PCR analysis. The effect of PAP on dopaminergic neuronal cell death and neurotrophic factors were determined by immunohistochemistry and Western blot analysis. To assess mouse locomotor activity, rotarod and pole tests were performed in MPTP-injected mice.

Results
PAP inhibited the production of nitric oxide and proinflammatory cytokines in LPS-stimulated microglia by modulating various inflammatory signals. In addition, PAP elevated intracellular cAMP levels and CREB phosphorylation. Treatment with H89, a PKA inhibitor, reversed the anti-inflammatory effects of PAP, suggesting the critical role of PKA signaling in the anti-inflammatory effects of PAP. We verified the anti-inflammatory effects of PAP in the brains of mice with LPS-induced systemic inflammation. PAP suppressed microglial activation and proinflammatory gene expression in the brains of these mice, and these effects were reversed by H89 treatment. We further examined the effects of PAP on MPTP-injected PD model mice. MPTP-induced dopaminergic neuronal cell death and impaired locomotor activity were recovered by PAP. In addition, PAP suppressed microglial activation and proinflammatory mediators in the brains of MPTP-injected mice.

Conclusions
PAP has strong anti-inflammatory and neuroprotective effects and thus may be a potential candidate for treating neuroinflammatory disorders such as PD.
Antiviral activities of extremophilic actinomycetes extracts from Kazakhstan’s unique ecosystems against influenza viruses and paramyxoviruses
Authors: Berezin Vladimir , Abdukhakimova Diyora , Trenozhnikova Lyudmila , Bogoyavlenskiy Andrey , Turmagambetova Aizhan , Issanov Alpamys , Azizan Azliyati 
Published: December 2019

Abstract
Background
Commercially available antiviral drugs, when used in the treatment of viral infections, do not always result in success. This is an urgent problem currently that needs to be addressed because several viruses including influenza and paramyxoviruses are acquiring multi-drug resistance. A potential solution for this emerging issue is to create new antiviral drugs from available compounds of natural products. It is known that the majority of drugs have been developed using compounds derived from actinomycetes, which are naturally occurring gram-positive bacteria. The purpose of this study was to investigate the antiviral properties of extremophilic actinomycetes extracts from strains that were isolated from extreme environments in Kazakhstan.

Methods
Five strains of extremophilic actinomycetes isolated from the unique ecosystems of Kazakhstan were extracted and tested for antiviral activity against influenza viruses (strains H7N1, H5N3, H1N1 and H3N2) and paramyxoviruses (Sendai Virus and Newcastle Disease Virus). The antiviral activity of these selected extracts was tested by checking their effect on hemagglutination and neuraminidase activities of the studied viruses. Additionally, actinomycetes extracts were compared with commercially available antiviral drugs and some plant preparations that have been shown to exhibit antiviral properties.

Results
The main findings show that extracts from strains K-192, K-340, K-362, K-522 and K525 showed antiviral activities when tested using influenza viruses, Sendai Virus, and Newcastle Disease Virus. These activities were comparable to those shown by Rimantadine and Tamiflu drugs, and “Virospan” and “Flavovir” plant preparations.

Conclusions
We identified several extracts with antiviral activities against several strains of influenza viruses and paramyxoviruses. Our research findings can be applied towards characterization and development of new antiviral drugs from the active actinomycetes extracts.