bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel oxygen saturation imaging endoscopy to assess anastomotic integrity in a porcine ischemia model
Authors: Hasegawa Hiro , Takeshita Nobuyoshi , Ito Masaaki 
Published: October 2020

Abstract
Background
Establishing anastomotic integrity is crucial for avoiding anastomotic complications in colorectal surgery. This study aimed to evaluate the safety and feasibility of assessing anastomotic integrity using novel oxygen saturation imaging endoscopy in a porcine ischemia model.

Methods
In three pigs, a new endoscope system was used to check the mechanical completeness of the anastomosis and capture the tissue oxygen saturation (StO2) images. This technology can derive the StO2 images from the differences in the absorption coefficient in the visible light region between oxy- and deoxy-hemoglobin. Bowel perfusion at the proximal rectum was assessed before and after the anastomosis, and 1 min and 30 min after the ligation of the cranial rectal artery (CRA).

Results
The completeness of the anastomoses was confirmed by the absence of air leakage. Intraluminal oxygen saturation imaging was successfully performed in all animals. There was no significant difference in the StO2 level before and after the anastomosis (52.6 ± 2.0 vs. 52.0 ± 2.6; p = 0.76, respectively). The StO2 level of the intestine on the oral side of the anastomosis one minute after the CRA ligation was significantly lower than immediately after the anastomosis (15.9 ± 6.0 vs. 52.0 ± 2.6; p = 0.006, respectively). There was no significant difference in the StO2 level between 1 min after and 30 min after the CRA ligation (15.9 ± 6.0 vs. 12.1 ± 5.3; p = 0.41, respectively).

Conclusion
Novel oxygen saturation imaging endoscopy was safe and feasible to assess the anastomotic integrity in the experimental model.
The efficacy of specialised rehabilitation using the Op-reha Guide for cancer patients in palliative care units: protocol of a multicentre, randomised controlled trial (JORTC-RHB02)
Authors: Nishiyama Nanako , Matsuda Yoshinobu , Fujiwara Noriko , Ariyoshi Keisuke , Oyamada Shunsuke , Narita Keiichi , Ishii Ryouhei , Iwase Satoru 
Published: October 2020

Abstract
Background
Although rehabilitation is recommended for terminal cancer patients, the specific components and methods of such programs are poorly documented. No studies to date have examined the effectiveness of rehabilitation for terminal cancer patients. This study aims to evaluate the efficacy of a new intervention for rehabilitation therapists, using the Op-reha Guide (Guide to Optimal and Patient-Centred Rehabilitation Practice for Patients in Palliative Care Units [PCUs]) in rehabilitation practice. This guide consists of recommended actions and attitudes for rehabilitation therapists and aims to optimise therapists’ actions according to the patient’s needs and condition. It shares goals with terminal cancer patients to maintain their activities of daily living (ADL).

Methods
This study uses a multicentre, prospective, randomised controlled trial (RCT) design with two parallel groups in PCUs where specialised rehabilitation will be routinely performed for terminal cancer patients by rehabilitation therapists. Participants will be randomised (1:1) to intervention (the Op-reha Guide) and control groups (usual rehabilitation). We will then conduct an observational study in PCUs that do not perform specialised rehabilitation for terminal cancer patients; this will be considered the usual care group, and the efficacy of usual rehabilitation will be quantitatively evaluated. Inclusion criteria are hospitalisation in PCU, European Cooperative Oncology Group Performance Status of 2 or 3, and clinical estimation of life expectancy of 3 weeks or more. Patients with severe symptom burden will be excluded. We hypothesise that the Op-reha Guide will be more effective in maintaining the ADL of terminal cancer patients hospitalised in PCUs than usual rehabilitation. The primary endpoint is defined as the change in (total) modified Barthel Index from baseline to Day 22. Quality of life will be a secondary endpoint. In total, 135 patients will be recruited from 16 Japanese sites between July 2019 and December 2021.

Discussion
This will be the first trial to evaluate the efficacy of specialised rehabilitation for terminal cancer patients hospitalised in PCUs, and will contribute to the evidence on the efficacy of implementing rehabilitation for terminal cancer patients.

Trial registration
UMIN-CTR, UMIN000037298 R000042525 (date of registration 7 July 2019).
NMR and LCMS analytical platforms exhibited the nephroprotective effect of Clinacanthus nutans in cisplatin-induced nephrotoxicity in the in vitro condition
Authors: Mahmod Ilya Iryani , Ismail Intan Safinar , Alitheen Noorjahan Banu , Normi Yahaya M. , Abas Faridah , Khatib Alfi , Rudiyanto  , Latip Jalifah 
Published: October 2020

Abstract
Background
Clinacanthus nutans (C. nutans) Lind. locally known as Belalai Gajah or Sabah snake grass is a medicinal plant belonging to Acanthaceae family. In Asia, this plant is traditionally used for treating skin rashes, insects and snake bites, diabetes mellitus, fever and for diuretic effect. C. nutans has been reported to possess biological activities including anti-oxidant, anti-inflammation, anti-cancer, anti-diabetic and anti-viral activities.

Methods
Proton Nuclear Magnetic Resonance (1H NMR) and Liquid Chromatography Mass Spectroscopy (LCMS) coupled with multivariate data analysis were employed to characterize the metabolic variations of intracellular metabolites and the compositional changes of the corresponding culture media in rat renal proximal tubular cells (NRK-52E).

Results
NMR and LCMS analysis highlighted choline, creatine, phosphocholine, valine, acetic acid, phenylalanine, leucine, glutamic acid, threonine, uridine and proline as the main metabolites which differentiated the cisplatin-induced group of NRK-52E from control cells extract. The corresponding media exhibited lactic acid, glutamine, glutamic acid and glucose-1-phosphate as the varied metabolites. The altered pathways perturbed by cisplatin nephrotoxic on NRK-52E cells included changes in amino acid metabolism, lipid metabolism and glycolysis.

Conclusion
The C. nutans aqueous extract (1000 μg/mL) exhibited the most potential nephroprotective effect against cisplatin toxicity on NRK-52E cell lines at 89% of viability. The protective effect could be seen through the changes of the metabolites such as choline, alanine and valine in the C. nutans pre-treated samples with those of the cisplatin-induced group.
Genetic diversity of circumsporozoite protein in Plasmodium knowlesi isolates from Malaysian Borneo and Peninsular Malaysia
Authors: Chong Eric Tzyy Jiann , Neoh Joveen Wan Fen , Lau Tiek Ying , Lim Yvonne Ai-Lian , Chai Hwa Chia , Chua Kek Heng , Lee Ping-Chin 
Published: October 2020

Abstract
Background
Understanding the genetic diversity of candidate genes for malaria vaccines such as circumsporozoite protein (csp) may enhance the development of vaccines for treating Plasmodium knowlesi. Hence, the aim of this study is to investigate the genetic diversity of non-repeat regions of csp in P. knowlesi from Malaysian Borneo and Peninsular Malaysia.

Methods
A total of 46 csp genes were subjected to polymerase chain reaction amplification. The genes were obtained from P. knowlesi isolates collected from different divisions of Sabah, Malaysian Borneo, and Peninsular Malaysia. The targeted gene fragments were cloned into a commercial vector and sequenced, and a phylogenetic tree was constructed while incorporating 168 csp sequences retrieved from the GenBank database. The genetic diversity and natural evolution of the csp sequences were analysed using MEGA6 and DnaSP ver. 5.10.01. A genealogical network of the csp haplotypes was generated using NETWORK ver. 4.6.1.3.

Results
The phylogenetic analysis revealed indistinguishable clusters of P. knowlesi isolates across different geographic regions, including Malaysian Borneo and Peninsular Malaysia. Nucleotide analysis showed that the csp non-repeat regions of zoonotic P. knowlesi isolates obtained in this study underwent purifying selection with population expansion, which was supported by extensive haplotype sharing observed between humans and macaques. Novel variations were observed in the C-terminal non-repeat region of csp.

Conclusions
The csp non-repeat regions are relatively conserved and there is no distinct cluster of P. knowlesi isolates from Malaysian Borneo and Peninsular Malaysia. Distinctive variation data obtained in the C-terminal non-repeat region of csp could be beneficial for the design and development of vaccines to treat P. knowlesi.
Changes in the frequencies of Plasmodium falciparum dhps and dhfr drug-resistant mutations in children from Western Kenya from 2005 to 2018: the rise of Pfdhps S436H
Authors: Pacheco M. Andreína , Schneider Kristan A. , Cheng Qiuying , Munde Elly O. , Ndege Caroline , Onyango Clinton , Raballah Evans , Anyona Samuel B. , Ouma Collins , Perkins Douglas J. , Escalante Ananias A. 
Published: October 2020

Abstract
Background
Sulfadoxine-pyrimethamine (SP) is the only anti-malarial drug formulation approved for intermittent preventive treatment in pregnancy (IPTp). However, mutations in the Plasmodium falciparum dhfr (Pfdhfr) and dhps (Pfdhps) genes confer resistance to pyrimethamine and sulfadoxine, respectively. Here, the frequencies of SP resistance-associated mutations from 2005 to 2018 were compared in samples from Kenyan children with malaria residing in a holoendemic transmission region.

Methods
Partial sequences of the Pfdhfr and Pfdhps genes were amplified and sequenced from samples collected in 2005 (n = 81), 2010 (n = 95), 2017 (n = 43), and 2018 (n = 55). The frequency of known mutations conferring resistance to pyrimethamine and sulfadoxine were estimated and compared. Since artemisinin-based combination therapy (ACT) is the current first-line treatment for malaria, the presence of mutations in the propeller domain of P. falciparum kelch13 gene (Pfk13) linked to ACT-delayed parasite clearance was studied in the 2017/18 samples.

Results
Among other changes, the point mutation of Pfdhps S436H increased in frequency from undetectable in 2005 to 28% in 2017/18. Triple Pfdhfr mutant allele (CIRNI) increased in frequency from 84% in 2005 to 95% in 2017/18, while the frequency of Pfdhfr double mutant alleles declined (allele CICNI from 29% in 2005 to 6% in 2017/18, and CNRNI from 9% in 2005 to undetectable in 2010 and 2017/18). Thus, a multilocus Pfdhfr/Pfdhps genotype with six mutations (HGEAA/CIRNI), including Pfdhps S436H, increased in frequency from 2010 to 2017/18. Although none of the mutations associated with ACT-delayed parasite clearance was observed, the Pfk13 mutation A578S, the most widespread Pfk13 SNP found in Africa, was detected in low frequency (2.04%).

Conclusions
There were changes in SP resistance mutant allele frequencies, including an increase in the Pfdhps S436H. Although these patterns seem consistent with directional selection due to drug pressure, there is a lack of information to determine the actual cause of such changes. These results suggest incorporating molecular surveillance of Pfdhfr/Pfdhps mutations in the context of SP efficacy studies for intermittent preventive treatment in pregnancy (IPTp).
Isolation of exosomes from whole blood by a new microfluidic device: proof of concept application in the diagnosis and monitoring of pancreatic cancer
Authors: Sancho-Albero María , Sebastián Víctor , Sesé Javier , Pazo-Cid Roberto , Mendoza Gracia , Arruebo Manuel , Martín-Duque Pilar , Santamaría Jesús 
Published: October 2020

Abstract
Background
Exosomes are endocytic-extracellular vesicles with a diameter around 100 nm that play an essential role on the communication between cells. In fact, they have been proposed as candidates for the diagnosis and the monitoring of different pathologies (such as Parkinson, Alzheimer, diabetes, cardiac damage, infection diseases or cancer).

Results
In this study, magnetic nanoparticles (Fe3O4NPs) were successfully functionalized with an exosome-binding antibody (anti-CD9) to mediate the magnetic capture in a microdevice. This was carried out under flow in a 1.6 mm (outer diameter) microchannel whose wall was in contact with a set of NdFeB permanent magnets, giving a high magnetic field across the channel diameter that allowed exosome separation with a high yield. To show the usefulness of the method, the direct capture of exosomes from whole blood of patients with pancreatic cancer (PC) was performed, as a proof of concept. The captured exosomes were then subjected to analysis of CA19-9, a protein often used to monitor PC patients.

Conclusions
Here, we describe a new microfluidic device and the procedure for the isolation of exosomes from whole blood, without any need of previous isolation steps, thereby facilitating translation to the clinic. The results show that, for the cases analyzed, the evaluation of CA19-9 in exosomes was highly sensitive, compared to serum samples.
Understanding the crisis in harm reduction funding in Central and Eastern Europe
Authors: Miovský Michal , Miklíková Silvia , Mravčík Viktor , Grund Jean-Paul , Černíková Tereza 
Published: October 2020

Abstract
Background
The harm reduction (HR) approach to injecting drug use was rapidly adopted in Central Europe following the fall of the Iron Curtain. The associated social and economic transformation had significant consequences for drug policies in the region. A large number of emerging services have been dependent on funding from a wide range of national and/or local funding programmes, which continue to be unstable, and closely associated with political decisions and insufficient institution building.
A sharp distinction is made between health and social services, often without regard to client input. The main objective of the paper is to identify the causes of the funding problems currently faced by HR services in the context of their history of institution building which represents a major threat to the future of HR services in the region.

Methods
Qualitative content analysis of documents was conducted in the development of two case studies of the Czech and Slovak Republics. The body of documentation under study comprised policy documents, including National Drug Strategies, Action Plans, ministerial documents, and official budgets and financial schedules, as well as documents from the grey literature and expert opinions.

Results
The insufficient investments in finalising the process of the institution building of HR services have resulted in a direct threat to their sustainability. An unbalanced inclination to the institutionalisation of HR within the domain of social services has led to a misperception of their integrity, as well as to their funding and long-term sustainability being endangered. In addition, this tendency has had a negative impact on the process of the institutionalisation of HR within the system of healthcare.

Conclusion
The case study revealed a lack of systemic grounding of HR services as interdisciplinary health-social services. The aftermath of the financial crisis in 2008 fully revealed the limitations of the funding system established ad hoc in the 1990s, which remains present until today, together with all its weak points. The entire situation is responsible for the dangerous erosion of the interpretation of the concept of harm reduction, which is supported by various stereotypes and false, or ideological, interpretations of the concept.
A risk stratification model based on four novel biomarkers predicts prognosis for patients with renal cell carcinoma
Authors: Kubota Shigehisa , Yoshida Tetsuya , Kageyama Susumu , Isono Takahiro , Yuasa Takeshi , Yonese Junji , Kushima Ryoji , Kawauchi Akihiro , Chano Tokuhiro 
Published: October 2020

Abstract
Background

Accurate prediction of the prognosis of RCC using a single biomarker is challenging due to the genetic heterogeneity of the disease. However, it is essential to develop an accurate system to allow better patient selection for optimal treatment strategies. ARL4C, ECT2, SOD2, and STEAP3 are novel molecular biomarkers identified in earlier studies as survival-related genes by comprehensive analyses of 43 primary RCC tissues and RCC cell lines.

Methods

To develop a prognostic model based on these multiple biomarkers, the expression of four biomarkers ARL4C, ECT2, SOD2, and STEAP3 in primary RCC tissue were semi-quantitatively investigated by immunohistochemical analysis in an independent cohort of 97 patients who underwent nephrectomy, and the clinical significance of these biomarkers were analyzed by survival analysis using Kaplan-Meier curves. The prognostic model was constructed by calculation of the contribution score to prognosis of each biomarker on Cox regression analysis, and its prognostic performance was validated.

Results

Patients whose tumors had high expression of the individual biomarkers had shorter cancer-specific survival (CSS) from the time of primary nephrectomy. The prognostic model based on four biomarkers segregated the patients into a high- and low-risk scored group according to defined cut-off value. This approach was more robust in predicting CSS compared to each single biomarker alone in the total of 97 patients with RCC. Especially in the 36 metastatic RCC patients, our prognostic model could more accurately predict early events within 2 years of diagnosis of metastasis. In addition, high risk-scored patients with particular strong SOD2 expression had a much worse prognosis in 25 patients with metastatic RCC who were treated with molecular targeting agents.

Conclusions

Our findings indicate that a prognostic model based on four novel biomarkers provides valuable data for prediction of clinical prognosis and useful information for considering the follow-up conditions and therapeutic strategies for patients with primary and metastatic RCC.
Sphingosine-1-phosphate receptor subtype 1 activation in the central nervous system contributes to morphine withdrawal in rodents
Authors: Doyle Timothy M. , Hutchinson Mark R. , Braden Kathryn , Janes Kali , Staikopoulos Vicky , Chen Zhoumou , Neumann William L. , Spiegel Sarah , Salvemini Daniela 
Published: October 2020

AbstractOpioid therapies for chronic pain are undermined by many adverse side effects that reduce their efficacy and lead to dependence, abuse, reduced quality of life, and even death. We have recently reported that sphingosine-1-phosphate (S1P) 1 receptor (S1PR1) antagonists block the development of morphine-induced hyperalgesia and analgesic tolerance. However, the impact of S1PR1 antagonists on other undesirable side effects of opioids, such as opioid-induced dependence, remains unknown. Here, we demonstrate that naloxone-precipitated morphine withdrawal in mice altered de novo sphingolipid metabolism in the dorsal horn of the spinal cord and increased S1P that accompanied the manifestation of several withdrawal behaviors. Blocking de novo sphingolipid metabolism with intrathecal administration of myriocin, an inhibitor of serine palmitoyltransferase, blocked naloxone-precipitated withdrawal. Noteworthy, we found that competitive (NIBR-15) and functional (FTY720) S1PR1 antagonists attenuated withdrawal behaviors in mice. Mechanistically, at the level of the spinal cord, naloxone-precipitated withdrawal was associated with increased glial activity and formation of the potent inflammatory/neuroexcitatory cytokine interleukin-1β (IL-1β); these events were attenuated by S1PR1 antagonists. These results provide the first molecular insight for the role of the S1P/S1PR1 axis during opioid withdrawal. Our data identify S1PR1 antagonists as potential therapeutics to mitigate opioid-induced dependence and support repurposing the S1PR1 functional antagonist FTY720, which is FDA-approved for multiple sclerosis, as an opioid adjunct.
Gut bacteria Akkermansia is associated with reduced risk of obesity: evidence from the American Gut Project
Authors: Zhou Qi , Zhang Yanfeng , Wang Xiaoxia , Yang Ruiyue , Zhu Xiaoquan , Zhang Ying , Chen Chen , Yuan Huiping , Yang Ze , Sun Liang 
Published: October 2020

Abstract
Background
Gut bacteria Akkermansia has been shown an anti-obesity protective effect in previous studies and may be used as promising probiotics. However, the above effect may be confounded by common factors, such as sex, age and diets, which should be verified in a generalized population.

Methods
We used datasets from the American Gut Project to strictly reassess the association and further examined the effect of aging on it. A total of 10,534 participants aged 20 to 99 years from the United States and the United Kingdom were included. The relative abundance of Akkermansia was assessed based on 16S rRNA sequencing data. Obesity (body mass index, BMI ≥ 30 kg/m2) risks were compared across Akkermansia quintiles in logistic models with adjustment for common confounders. Restricted cubic splines were used to examine dose response effects between Akkermansia, obesity and age. A sliding-windows-based algorithm was used to investigate the effect of aging on Akkermansia-obesity associations.

Results
The median abundance of Akkermansia was 0.08% (interquartile range: 0.006–0.93%), and the prevalence of obesity was 11.03%. Nonlinear association was detected between Akkermansia and obesity risk (P = 0.01). The odds ratios (95% confidence interval) for obesity across the increasing Akkermansia quintiles (referencing to the first quintile) were 1.14 (0.94–1.39), 0.94 (0.77–1.15), 0.70 (0.56–0.85) and 0.79 (0.64–0.96) after adjusting for age and sex (P for trend < 0.001). This association remained unchanged after further controlling for smoking, alcohol drinking, diet, and country. The odds ratios (95% CI) of Akkermansia were 0.19 (0.03–0.62) and 0.77 (0.64–0.91) before and over 40 years, respectively, indicating that the protective effect of Akkermansia against obesity was not stable with aging.

Conclusion
High relative abundance of Akkermansia is associated with low risk of obesity and the association declines with aging.
Data and cooperation required for Venezuela’s refugee crisis during COVID-19
Authors: Standley Claire J. , Chu Eric , Kathawala Emrose , Ventura Deisy , Sorrell Erin M. 
Published: October 2020

AbstractThe deteriorating political and economic situation in Venezuela has ramifications far beyond the Latin American country’s borders as almost five million Venezuelans fled and migrated into countries in the region due to the crisis at home. The scarcity of health services, the lack of information sharing, and the absence of reliable data in Venezuela create challenges for confronting developing health emergencies and disease outbreaks. The need for accurate data is especially dire given the current COVID-19 pandemic and evolving movement of refugees. While countries and international organizations came together to form a coordinated response to Venezuela’s political and humanitarian crisis, this geopolitical progress is threatened by the rapid spread of COVID-19, and the instinct for countries to focus inwards on domestic response priorities, rather than engage in regional cooperation. It is critical that the international community set aside geopolitical differences and cooperate to seek an accurate picture of the conditions on the ground to improve the welfare of Venezuelan migrants and to provide a more robust response to the current pandemic.