bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of surgical resection for gastric cancer liver metastases: a retrospective analysis
Authors: Kawahara Kenji , Makino Hironobu , Kametaka Hisashi , Hoshino Isamu , Fukada Tadaomi , Seike Kazuhiro , Kawasaki Yohei , Otsuka Masayuki 
Published: February 2020

Abstract
Background
The indications for the surgical treatment of gastric cancer liver metastases (GCLMs) remain controversial. In addition, the outcome of surgery for the treatment of liver metastases of alpha-fetoprotein-producing gastric cancer (AFP-GC) has not yet been reported. We assessed the clinicopathologic features, including AFP-GC, and the surgical results of these patients.

Methods
This retrospective study analyzed 20 patients who underwent hepatectomy for GCLM at Odawara Municipal Hospital between April 2006 and January 2016.

Results
The actuarial 1-, 3-, and 5-year overall survival (OS) rates after primary hepatectomy were 80.0%, 55.5%, and 31.7%, respectively, with a median OS of 42 months. Four patients survived for more than 5 years after their final hepatectomy procedures. A multivariate analysis showed multiple metastases in the liver, the elevated level of carbohydrate antigen 19-9 (CA19-9), and an age of less than 70 years to be independently associated with a poor prognosis in terms of OS. No significant differences were noted between the AFP-GC and AFP-negative GC groups.

Conclusion
Surgical treatment is therefore considered to be a feasible option for GCLM. The findings of the present study showed the number of metastatic liver tumors, the level of CA19-9, and the patient age to be prognostic indicators for the surgical treatment of GCLM.
Identification and clinical impact of potentially actionable somatic oncogenic mutations in solid tumor samples
Authors: Toomey Sinead , Carr Aoife , Mezynski Mateusz Janusz , Elamin Yasir , Rafee Shereen , Cremona Mattia , Morgan Clare , Madden Stephen , Abdul-Jalil Khairun I. , Gately Kathy , Farrelly Angela , Kay Elaine W. , Kennedy Susan , O’Byrne Kenneth , Grogan Liam , Breathnach Oscar , Morris Patrick G. , Eustace Alexander J. , Fay Joanna , Cummins Robert , O’Grady Anthony , Kalachand Roshni , O’Donovan Norma , Kelleher Fergal , O’Reilly Aine , Doherty Mark , Crown John , Hennessy Bryan T. 
Published: February 2020

Abstract
Background
An increasing number of anti-cancer therapeutic agents target specific mutant proteins that are expressed by many different tumor types. Successful use of these therapies is dependent on the presence or absence of somatic mutations within the patient’s tumor that can confer clinical efficacy or drug resistance.

Methods
The aim of our study was to determine the type, frequency, overlap and functional proteomic effects of potentially targetable recurrent somatic hotspot mutations in 47 cancer-related genes in multiple disease sites that could be potential therapeutic targets using currently available agents or agents in clinical development.

Results
Using MassArray technology, of the 1300 patient tumors analysed 571 (43.9%) had at least one somatic mutation. Mutations were identified in 30 different genes. KRAS (16.5%), PIK3CA (13.6%) and BRAF (3.8%) were the most frequently mutated genes. Prostate (10.8%) had the lowest number of somatic mutations identified, while no mutations were identified in sarcoma. Ocular melanoma (90.6%), endometrial (72.4%) and colorectal (66.4%) tumors had the highest number of mutations. We noted high concordance between mutations in different parts of the tumor (94%) and matched primary and metastatic samples (90%). KRAS and BRAF mutations were mutually exclusive. Mutation co-occurrence involved mainly PIK3CA and PTPN11, and PTPN11 and APC. Reverse Phase Protein Array (RPPA) analysis demonstrated that PI3K and MAPK signalling pathways were more altered in tumors with mutations compared to wild type tumors.

Conclusions
Hotspot mutational profiling is a sensitive, high-throughput approach for identifying mutations of clinical relevance to molecular based therapeutics for treatment of cancer, and could potentially be of use in identifying novel opportunities for genotype-driven clinical trials.
Acute and chronic effects of multivitamin/mineral supplementation on objective and subjective energy measures
Authors: Dodd F. L. , Kennedy D. O. , Stevenson E. J. , Veasey R. C. , Walker K. , Reed S. , Jackson P. A. , Haskell-Ramsay C. F. 
Published: February 2020

Abstract
Background
Vitamins and minerals play an essential role within many cellular processes including energy production and metabolism. Previously, supplementation with a multivitamin/mineral (MVM) for ≥28 days resulted in improvements to cognition and subjective state. We have also demonstrated shifts in metabolism during cognitively demanding tasks following MVM in females, both acutely and following 8-week supplementation. The current study aimed to assess these effects further in males and females using metabolically challenging exercise and cognitive tasks.

Methods
The current randomised, placebo-controlled, parallel groups study investigated the effects of a MVM complex in 82 healthy young (18-35y) exercisers. Subjective ratings and substrate metabolism were assessed during 30 min each of increasingly effortful incremental exercise and demanding cognitive tasks. Assessments took place on acute study days following a single dose (Day 1) of MVM, containing 3 times recommended daily allowance of water-soluble vitamins plus CoQ10, and following 4-week supplementation (Day 28).

Results
Energy expenditure (EE) was increased during cognitive tasks following MVM across Day 1 and Day 28, with greater effects in males. In males, MVM also increased carbohydrate oxidation and energy expenditure during exercise across Day 1 and Day 28. In females, mental tiredness was lower during exercise; increases in physical tiredness following 30 min of exercise were attenuated; and stress ratings following cognitive tasks were reduced following MVM. In males, MVM only lowered mental tiredness following 10 min of exercise. These effects were apparent irrespective of day, but effects on mental tiredness were greater on Day 28. Ferritin levels were also higher on Day 28 in those receiving MVM.

Conclusion
These findings extend on existing knowledge, demonstrating increased carbohydrate oxidation and increased energy expenditure in males following MVM supplementation for the first time. Importantly, they show modulation of energy expenditure and subjective tiredness following a single dose, providing further evidence for acute effects of MVM. Differential effects in men and women suggest that sex may play an important role in the effects of MVM on energy metabolism and should be considered in future research.

Trial registration
ClinicalTrials.gov, NCT03003442. Registered 22nd November 2016 – retrospectively registered
Leaving no one behind: lessons from implementation of policies for universal HIV treatment to universal health coverage
Authors: Assefa Yibeltal , Hill Peter S. , Van Damme Wim , Dean Judith , Gilks Charles F. 
Published: February 2020

Abstract
Background
The third Sustainable Development Goal (SDG − 3) aims to ensure healthy lives and promote well-being for all at all ages. SDG-3 has a specific target on universal health coverage (UHC), which emphasizes the importance of all people and communities having access to quality health services without risking financial hardship. The objective of this study is to review progress towards UHC using antiretroviral treatment (ART) as a case study.

Methods
We used a mixed-methods design including qualitative and quantitative approaches. We reviewed and synthesised the evidence on the evolution of the WHO HIV treatment guidelines between 2002 and 2019. We calculated ART coverage over time by gender, age group, and location. We also estimated ART coverage differences and ratios.

Findings
ART guidelines have evolved from “treating the sickest” to “treating all”. ART coverage increased globally from under 7% in 2005 to 62% in 2018. There have been successes in increasing ART coverage in all populations and locations. However, progress varies by population and location in many regions. There is inequity in ART coverage: women (68%) versus men (55%), and adults (62%) versus children (54%). This inequity has widened over time, and with expanded ART eligibility criteria. On the other hand, data from at least one high-burden country (Ethiopia) shows that inequity among regions has narrowed over time due to the improvements in the primary health care systems and implementation of the public health approach in the country.

Conclusion
ART coverage has increased at global, regional and national levels to all population groups. However, the gains have not been equitable among locations and populations. Policies towards universality may widen the inequity in resource-limited settings unless countries take precautions and “put the last first”. We argue that primary health care and public health approaches, with multi-sectoral actions and community engagement, are vital to minimize inequity, achieve UHC and leave no one behind.
“The sweet and the bitter”: mothers’ experiences of breastfeeding in the early postpartum period: a qualitative exploratory study in China
Authors: Xiao Xiao , Loke Alice Yuen , Zhu She-ning , Gong Lin , Shi Hong-mei , Ngai Fei-wan 
Published: February 2020

Abstract
Background
In China, the prevalence of exclusive breastfeeding at 6 months was only 20.8%. In promoting breastfeeding for newborns, a number of strategies have been initiated by Chinese government. These actions facilitated a high breastfeeding initiation of 77 to 99.9% in different regions. However, the exclusive breastfeeding rates remained low at 6 months resulting from a high rate of perceived insufficient breast milk and complementary feeding during the early days after childbirth. The aim of this study was to understand the experiences of women in Shenzhen with regard to breastfeeding in the first 6 weeks after giving birth, to identify the facilitators and barriers impacting their breastfeeding decisions and to identify their perceived support needs that might facilitate breastfeeding in the future.

Methods
This was a qualitative exploratory study. Data were collected in November 2018 through semi-structured, face-to-face, in-depth interviews. A purposive sample of early postpartum women was recruited from a postpartum clinic of a tertiary maternal hospital in Shenzhen, China. The dataset was analysed using inductive content analysis.

Results
A total of 22women were interviewed within the first 6 weeks after delivery. Three themes related to breastfeeding were identified from the transcribed interviews: “breastfeeding facilitators,” “breastfeeding barriers,” and “recommendations for breastfeeding promotion.”

Conclusions
Women experienced both joy and suffering in their journey of breastfeeding. Insufficient knowledge of breastfeeding, discomfort, intergenerational disagreements regarding nutritional supplements, and a lack of professional support contributed to difficulties and the threat of discontinuation. A supportive environment for breastfeeding is crucial for women’s decision on exclusive breastfeeding and the psychological wellbeing of breastfeeding women. Interventions that target to promote exclusive breastfeeding should include both new mothers and significant family members. Future studies could test the effectiveness of breastfeeding training for home visit nurses to promote exclusive breastfeeding in the early postpartum.
Benzodiazepines in the oral fluid of Spanish drivers
Authors: Herrera-Gómez Francisco , García-Mingo Mercedes , Álvarez F. Javier 
Published: February 2020

Abstract
Background
Driving under the influence of alcohol, illicit drugs and certain medicines is not allowed worldwide. Roadside drug testing is considered an important tool for determining such behavior. In Spain, mandatory roadside oral fluid drug testing is carried out regularly. The aim of this study was to determine the prevalence of benzodiazepines and benzodiazepines in combination with other drugs in drivers, examine benzodiazepine concentrations in drivers, and analyze the association of these factors with age and sex.

Methods
This study assessed data on Spanish drivers with confirmed drug-positive results recorded by the Spanish National Traffic Agency (Dirección General de Tráfico) between 2011 and 2016, accounting for 179,645 tests and 65,244 confirmed drug-positive tests.

Results
Benzodiazepines were confirmed in 4.3% of all positive roadside drug tests. In most of those cases (97.1%), other substances were also detected, particularly cocaine (75.3%) and cannabis (64.0%). The frequency of benzodiazepine-positive drivers (OR, 1.094; 95% CI, 1.088–1.100) increased with age, while the frequency of drivers who tested positive for benzodiazepines in conjunction with other substances, compared with drivers who tested positive for benzodiazepines alone, decreased with age (OR, 0.903; 95% CI, 0.825–0.988). Nordiazepam (54.8%) and alprazolam (46.9%) were the most common benzodiazepines detected.

Conclusion
Concomitant use of benzodiazepines and other psychoactive substances was found to be a common behavior among drivers who tested positive on the road. It is important to raise awareness of all those involved in the consumption of driving-impairing substances (authorities, healthcare providers, patients and their families, etc.): roadside detection of driving-impairing substances is suggested, in addition to promoting the use of fewer driving-impairing medications and the provision of clear information to patients.
Tracheo-innominate artery fistula with continuous bleeding successfully treated through the suprasternal approach: a case report
Authors: Kaneko Shotaro , Uchida Keiji , Karube Norihisa , Kasama Keiichiro , Minami Tomoyuki , Cho Tomoki , Izubuchi Ryo , Fushimi Kenichi , Yabu Naoto , Goda Motohiko , Masuda Munetaka 
Published: February 2020

Abstract
Background
Tracheo-innominate artery fistula (TIF) is a rare but fatal complication occurring after tracheotomy. Brachiocephalic trunk transection, one of the surgical treatments for TIF, is mostly associated with a full or partial median sternotomy. We describe a case of TIF with continuous bleeding, which was successfully treated with brachiocephalic trunk transection through a collar incision without the need for median sternotomy.

Case presentation
Case 1.
An 18-year-old man was referred to our hospital with bleeding from a tracheal stoma, which had ceased prior to admission. TIF was suspected after examination. Innominate artery transection was performed through a collar incision. TIF was not revealed when we cut the innominate artery anterior wall open; therefore, we opted for preventive surgical intervention. The post-operative course was uneventful, and the patient was asymptomatic at the 3-year follow-up.
Case 2.
A 14-year-old male patient was admitted to our hospital with bleeding from a tracheal stoma, and TIF was suspected after examination. There was persistent bleeding when the cuff of the tracheotomy tube was deflated. Brachiocephalic trunk transection was performed through a collar incision using balloon occlusion. The post-operative course was uneventful, and rebleeding has not occurred 2 years later.

Conclusions
Brachiocephalic trunk transection without any median sternotomy may offer the benefits of post-operative infection prevention. In patients with suspected continuous bleeding, using a balloon catheter may be a safe and effective method of treatment.
Biodegradation of penicillin G from industrial bacteria residue by immobilized cells of Paracoccus sp. KDSPL-02 through continuous expanded bed adsorption bioreactor
Authors: Wang Peng , Shen Chen , Wang Xiaochun , Liu Shouxin , Li Luwei , Guo Jinfeng 
Published: February 2020

Abstract
Background
An efficient biodegradation-strengthening approach was developed to improve penicillin G degradation from industrial bacterial residue in an expanded bed adsorption bioreactor (EBAB) is reported in this paper.

Results
Paracoccus sp. strain KDSPL-02 was isolated based on its ability to use penicillin G as the sole carbon and nitrogen source. Strain identification was based on analyses of morphology, physio-biochemical characteristics, and 16S rDNA sequences. The effects of temperature, pH, PVA-sodium alginate concentration, calcium chloride concentration and initial penicillin G concentration were investigated. Repeated operations of immobilized cells with EBAB, At initial penicillin concentrations below 2.0 g L− 1, the continuous mode could reach more than 20 times, and the degradation rate reached 100%.

Conclusions
The present study suggests that the EBAB system can be utilized for the simple and economical biodegradation of penicillin G from industrial bacterial residue.
A SUMOylation-dependent HIF-1α/CLDN6 negative feedback mitigates hypoxia-induced breast cancer metastasis
Authors: Jia Yiyang , Guo Yantong , Jin Qiu , Qu Huinan , Qi Da , Song Peiye , Zhang Xiaoli , Wang Xinqi , Xu Wenhong , Dong Yuan , Liang Yingying , Quan Chengshi 
Published: February 2020

Abstract
Background
We have previously described CLDN6 as a tumor suppressor gene in breast cancer. Here, a new finding is that CLDN6 was upregulated under hypoxia, a commonly recognized factor that promotes tumor metastasis. In this study, we aim to explain this confusing finding and delineate the role of CLDN6 in the breast cancer metastasis induced by hypoxia.

Methods
RNAi and ChIP assays were used to confirm that CLDN6 is transcriptional regulated by HIF-1α. mRNA seq and KEGG analysis were performed to define the downstream pathways of CLDN6. The roles of the CLDN6/SENP1/HIF-1α signaling on tumor metastasis were evaluated by function experiments and clinical samples. Finally, the possible transcription factor of SENP1 was suspected and then validated by ChIP assay.

Results
We demonstrated a previously unrecognized negative feedback loop exists between CLDN6 and HIF-1α. CLDN6 was transcriptionally up-regulated by HIF-1α under hypoxia. On the other hand, in cytoplasm CLDN6 combines and retains β-catenin, a transcription factor of SENP1, causing β-catenin degradation and preventing its nuclear translocation. This process reduced SENP1 expression and prevented the deSUMOylation of HIF-1α, ultimately leading to HIF-1α degradation and breast cancer metastasis suppression.

Conclusions
Our data provide a molecular mechanistic insight indicating that CLDN6 loss may lead to elevated HIF-1α-driven breast cancer metastasis in a SUMOylation-dependent manner.
The PLAGL2/MYCN/miR-506-3p interplay regulates neuroblastoma cell fate and associates with neuroblastoma progression
Authors: Zhao Zhenze , Shelton Spencer D. , Oviedo Alejandro , Baker Amy L. , Bryant Collin P. , Omidvarnia Soroush , Du Liqin 
Published: February 2020

AbstractBackgroundThe oncogene MYCN is critical for tumorigenesis of several types of cancers including neuroblastoma. We previously reported that miR-506-3p repressed MYCN expression in neuroblastoma cells. However, the mechanism underlying such regulation was undetermined since there is no miR-506-3p target site in MYCN 3’UTR.MethodsBy a systematic investigation combining microarray, informatics and luciferase reporter assay, we identified that the transcriptional factor pleiomorphic adenoma gene-like 2 (PLAGL2) is a direct target of miR-506-3p that mediates its regulation on MYCN expression. Using CHIP-PCR and luciferase reporter assay, we validated the transcriptional regulation of MYCN by PLAGL2 and we further demonstrated the transcriptional regulation of PLAGL2 by MYCN. We examined the function of PLAGL2 in regulating neuroblastoma cell fate by cell viability assay, colony formation and Western blotting of differentiation markers. We examined the effect of retinoic acid, the differentiation agent used in neuroblastoma therapy, on miR-506-3p, PLAGL2 and MYCN expressions by quantitative PCR and Western blots. We investigated the clinical relevance of PLAGL2 expression by examining the correlation of tumor PLAGL2 mRNA levels with MYCN mRNA expression and patient survival using public neuroblastoma patient datasets.ResultsWe found that miR-506-3p directly down-regulated PLAGL2 expression, and we validated a PLAGL2 binding site in the MYCN promoter region responsible for promoting MYCN transcription, thereby establishing a mechanism through which miR-506-3p regulates MYCN expression. Conversely, we discovered that MYCN regulated PLAGL2 transcription through five N-Myc-binding E-boxes in the PLAGL2 promoter region. We further confirmed the reciprocal regulation between endogenous PLAGL2 and MYCN in multiple neuroblastoma cell lines. Moreover, we found that PLAGL2 knockdown induced neuroblastoma cell differentiation and reduced cell proliferation, and combined knockdown of PLAGL2 and MYCN showed a synergistic effect. More strikingly, we found that high tumor PLAGL2 mRNA levels were significantly correlated with high MYCN mRNA levels and poor patient survival in neuroblastoma patients. Furthermore, we found that retinoic acid increased expression of miR-506-3p and repressed expression of MYCN and PLAGL2.ConclusionsOur findings altogether suggest that the interplay network formed by PLAGL2, MYCN and miR-506-3p is an important mechanism in regulating neuroblastoma cell fate, determining neuroblastoma prognosis, and mediating the therapeutic function of retinoic acid.
Prognostic value of venous blood analysis at the start of CPR in non-traumatic out-of-hospital cardiac arrest: association with ROSC and the neurological outcome
Authors: Corral Torres Ervigio , Hernández-Tejedor Alberto , Suárez Bustamante Rosa , de Elías Hernández Ramón , Casado Flórez Isabel , San Juan Linares Antonio 
Published: February 2020

Abstract
Background
The knowledge of new prognostic factors in out-of-hospital cardiac arrest (OHCA) that can be evaluated since the beginning of cardiopulmonary resuscitation (CPR) manoeuvres could be helpful in the decision-making process of prehospital care. We aim to identify metabolic variables at the start of advanced CPR at the scene that may be associated with two main outcomes of CPR (recovery of spontaneous circulation (ROSC) and neurological outcome).

Methods
Prospective observational study of all non-traumatic OHCA in patients older than 17 years assisted by emergency medical services (EMS), with doctor and nurse on board, between January 2012 and December 2017. Venous blood gases were sampled upon initially obtaining venous access to determine the initial values of pH, pCO2, HCO3−, base excess (BE), Na+, K+, Ca2+ and lactate. ROSC upon arrival at the hospital and neurological status 30 days later (Cerebral Performance Categories (CPC) scale) were recorded.

Results
We included 1552 patients with OHCA with blood test data in a 6-year period. ROSC was achieved in 906 cases (58.4%), and good neurological recovery at 30 days (CPC I-II) occurred in 383 cases (24.68%). In multivariate analysis, we found a significant relationship between non-recovery of spontaneous circulation (no-ROSC) and low pH levels (adjusted odds ratio (OR) 0.03 (0.002–0.59), p = 0.020), high pCO2 levels (adjusted OR 1.03 [1.01–1.05], p = 0.008) and high potassium levels (adjusted OR 2.28 [1.43–3.61], p = 0.008). Poor neurological outcomes were associated with low pH levels (adjusted OR 0.06 [0.02–0.18], p < 0.001), high pCO2 (adjusted OR 1.05 [1.03–1.08], p < 0.001), low HCO3− (adjusted OR 0.97 [0.94–0.999], p = 0.044), low BE (adjusted OR 0.96 [0.93–0.98], p < 0.001) and high potassium levels (adjusted OR 1.37 [1.16–1.60], p < 0.001).

Conclusion
There is a significant relationship between severe alterations of venous blood-gas variables and potassium at the start of CPR of non-traumatic OHCA and low-ROSC rate and neurological prognosis.