bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a communication skills training to facilitate addressing palliative care related topics in advanced cancer patients: study protocol of a multicenter randomized controlled trial (PALLI-KOM)
Authors: Harnischfeger Nele , Rath Hilke M. , Ullrich Anneke , Alt-Epping Bernd , Letsch Anne , Thuss-Patience Peter , Bokemeyer Carsten , Oechsle Karin , Bergelt Corinna 
Published: May 2020

Abstract
Background
Early integration of palliative care concurrently to standard cancer care is associated with several benefits for patients and their caregivers. However, communication barriers on part of the caring physicians often impede a timely referral to palliative care. This study describes the protocol of the evaluation of a communication skills training aiming to strengthen the ability of physicians to address palliative care related topics adequately and early during disease trajectory.

Methods
We will implement a communication skills training and evaluate it within a prospective, multi-centered, two-armed randomized controlled trial (RCT), which will be conducted at four sites in Germany. Eligible subjects are all physicians treating patients with advanced cancer in their daily routine. An intervention group (IG) receiving a group training will be compared to a wait-list control group (CG) receiving the training after completion of data collection. At pre- and post-measurement points, participants will conduct videotaped conversations with standardized simulated patients (SP). Primary outcome will be the external rating of communication skills and consulting competencies addressing palliative care related topics. Secondary outcomes on core concepts of palliative care, basic knowledge, attitudes, confidence and self-efficacy will be assessed by standardized questionnaires and self-developed items. A further external assessment of the quality of physician-patient-interaction will be conducted by the SP. Longitudinal quantitative data will be analyzed using covariate-adjusted linear mixed-models.

Discussion
If the communication skills training proves to be effective, it will provide a feasible intervention to promote an earlier communication of palliative care related topics in the care of advanced cancer patients. This would help to further establish early integration of palliative care as it is recommended by national and international guidelines.

Trial registration
German Clinical Trials Register DRKS00017025 (date of registration: 4 June 2019).
Efficacy and safety of myrrh in patients with incomplete abortion: a randomized, double-blind, placebo-controlled clinical study
Authors: Vafaei Homeira , Ajdari Sara , Hessami Kamran , Hosseinkhani Ayda , Foroughinia Leila , Asadi Nasrin , Faraji Azam , Abolhasanzadeh Sepideh , Bazrafshan Khadije , Roozmeh Shohreh 
Published: May 2020

Abstract
Background
Myrrh (Commiphora myrrha (Nees) Engl.) has a long history of traditional use as a herbal medicine for different purposes. In ancient traditional Persian manuscripts, it has been noted that myrrh may act as uterine stimulant and probably cause complete abortion. However, there is no evidence to verify this comment. Therefore, the current study was carried out to evaluate the efficacy and safety of Myrrh in the treatment of incomplete abortion.

Materials and methods
In a randomized double-blinded placebo controlled clinical trial, 80 patients with ultrasound-documented retained products of conception (RPOC) were assigned to receive capsules containing 500 mg of Myrrh oleo-gum-resin or a placebo three times a day for 2 weeks. The existence of the retained tissue and its size were evaluated by ultrasound examination at the beginning and end of the study.

Results
After 2 weeks, the mean diameter of the RPOC in the Myrrh group was significantly reduced compared with the placebo group (P < 0.001). Meanwhile, the rate of successful complete abortion was 82.9% in the intervention group and 54.3% in the placebo group (P = 0.01). The patients in both groups reported no serious drug-related adverse effects.

Conclusion
This study shows that Myrrh is effective and safe in the resolution of the RPOC and may be considered as an alternative option for treatment of patients with incomplete abortion. However, further studies on active compounds isolated from myrrh and their uterine stimulant effects are needed.

Trial registration
This study was retrospectively registered at Iranian Registry of Clinical Trials (www.irct.ir) IRCT code: IRCT20140317017034N7.
Engineering central pathways for industrial-level (3R)-acetoin biosynthesis in Corynebacterium glutamicum
Authors: Lu Lingxue , Mao Yufeng , Kou Mengyun , Cui Zhenzhen , Jin Biao , Chang Zhishuai , Wang Zhiwen , Ma Hongwu , Chen Tao 
Published: May 2020

Abstract
Background
Acetoin, especially the optically pure (3S)- or (3R)-enantiomer, is a high-value-added bio-based platform chemical and important potential pharmaceutical intermediate. Over the past decades, intense efforts have been devoted to the production of acetoin through green biotechniques. However, efficient and economical methods for the production of optically pure acetoin enantiomers are rarely reported. Previously, we systematically engineered the GRAS microorganism Corynebacterium glutamicum to efficiently produce (3R)-acetoin from glucose. Nevertheless, its yield and average productivity were still unsatisfactory for industrial bioprocesses.

Results
In this study, cellular carbon fluxes in the acetoin producer CGR6 were further redirected toward acetoin synthesis using several metabolic engineering strategies, including blocking anaplerotic pathways, attenuating key genes of the TCA cycle and integrating additional copies of the alsSD operon into the genome. Among them, the combination of attenuation of citrate synthase and inactivation of phosphoenolpyruvate carboxylase showed a significant synergistic effect on acetoin production. Finally, the optimal engineered strain CGS11 produced a titer of 102.45 g/L acetoin with a yield of 0.419 g/g glucose at a rate of 1.86 g/L/h in a 5 L fermenter. The optical purity of the resulting (3R)-acetoin surpassed 95%.

Conclusion
To the best of our knowledge, this is the highest titer of highly enantiomerically enriched (3R)-acetoin, together with a competitive product yield and productivity, achieved in a simple, green processes without expensive additives or substrates. This process therefore opens the possibility to achieve easy, efficient, economical and environmentally-friendly production of (3R)-acetoin via microbial fermentation in the near future.
A randomised controlled crossover trial investigating the short-term effects of different types of vegetables on vascular and metabolic function in middle-aged and older adults with mildly elevated blood pressure: the VEgetableS for vaScular hEaLth (VESSEL) study protocol
Authors: Connolly Emma L. , Bondonno Catherine P. , Sim Marc , Radavelli-Bagatini Simone , Croft Kevin D. , Boyce Mary C. , James Anthony P. , Clark Karin , Anokye Reindolf , Bondonno Nicola P. , Woodman Richard J. , Devine Amanda , Gan Seng Khee , Schultz Carl J. , Mithen Richard F. , Lewis Joshua R. , Hodgson Jonathan M. , Blekkenhorst Lauren C. 
Published: May 2020

Abstract
Background
A diet rich in fruits and vegetables is recommended for cardiovascular health. However, the majority of Australians do not consume the recommended number of vegetable servings each day. Furthermore, intakes of vegetables considered to have the greatest cardiovascular benefit are often very low. Results from prospective observational studies indicate that a higher consumption of cruciferous vegetables (e.g. broccoli, cabbage, cauliflower) is associated with lower cardiovascular disease risk. This may be due to the presence of specific nutrients and bioactive compounds found almost exclusively, or at relatively high levels, in cruciferous vegetables. Therefore, the aim of this randomised controlled crossover trial is to determine whether regular consumption of cruciferous vegetables results in short-term improvement in measures related to cardiovascular disease risk, including ambulatory blood pressure, arterial stiffness, glycaemic control, and circulating biomarkers of oxidative stress and inflammation.

Methods
Twenty-five participants (50–75 years) with mildly elevated blood pressure (systolic blood pressure 120–160 mmHg) will complete two 2-week intervention periods in random order, separated by a 2-week washout period. During the intervention period, participants will consume 4 servings (~ 300 g) of cruciferous vegetables per day as a soup (~ 500–600 mL/day). The ‘control’ soup will consist of other commonly consumed vegetables (potato, sweet potato, carrot, pumpkin). Both soups will be approximately matched for energy, protein, fat, and carbohydrate content. All measurements will be performed at the beginning and end of each intervention period.

Discussion
The findings of this study will provide evidence regarding the potential cardiometabolic health benefits of cruciferous vegetables, which may contribute to the revision of dietary and clinical guidelines.

Trial registration
The trial was registered with the Australian New Zealand Clinical Trial Registry on 19th September 2019 (ACTRN12619001294145).
The potential role of RNA N6-methyladenosine in Cancer progression
Authors: Wang Tianyi , Kong Shan , Tao Mei , Ju Shaoqing 
Published: May 2020

AbstractN6-methyladenosine (m6A) is considered the most common, abundant, and conserved internal transcript modification, especially in eukaryotic messenger RNA (mRNA). m6A is installed by m6A methyltransferases (METTL3/14, WTAP, RBM15/15B, VIRMA and ZC3H13, termed “writers”), removed by demethylases (FTO, ALKBH5, and ALKBH3, termed “erasers”), and recognized by m6A-binding proteins (YTHDC1/2, YTHDF1/2/3, IGF2BP1/2/3, HNRNP, and eIF3, termed “readers”). Accumulating evidence suggests that m6A RNA methylation greatly impacts RNA metabolism and is involved in the pathogenesis of many kinds of diseases, including cancers. In this review, we focus on the physiological functions of m6A modification and its related regulators, as well as on the potential biological roles of these elements in human tumors.
Clinical features and surgical outcomes of fibrolamellar hepatocellular carcinoma: retrospective analysis of a single-center experience
Authors: Lemekhova Anastasia , Hornuss Daniel , Polychronidis Georgios , Mayer Philipp , Rupp Christian , Longerich Thomas , Weiss Karl-Heinz , Büchler Markus , Mehrabi Arianeb , Hoffmann Katrin 
Published: May 2020

AbstractBackgroundClinicopathological features and surgical outcomes of patients with fibrolamellar hepatocellular carcinoma (FL-HCC) are underreported. The aim of this study is to describe clinical characteristics and surgical outcomes for patients with this rare tumor to raise awareness among clinicians and surgeons.MethodsRetrospective review of records of a tertiary referral center and specialized liver unit was performed. Out of 3623 patients who underwent liver resection, 366 patients received surgical treatment for HCC; of them, eight (2.2%) had FL-HCC and were resected between October 2001 and December 2018.ResultsEight patients (3 males and 5 females) with FL-HCC (median age 26 years) underwent primary surgical treatment. All patients presented with unspecific symptoms or were diagnosed as incidental finding. No patient had cirrhosis or other underlying liver diseases. Coincidentally, three patients (37.5%) had a thromboembolic event prior to admission. The majority of patients had BCLC stage C and UICC stage IIIB/IVA; four patients (50%) presented with lymph node metastases. The median follow-up period was 33.5 months. The 1-year survival was 71.4%, and 3-year survival was 57.1%. Median survival was at 36.4 months. Five patients (62.5%) developed recurrent disease after a median disease-free survival of 9 months. Two patients (25.0%) received re-resection.ConclusionFL-HCC is a rare differential diagnosis of liver masses in young patients. Since the prognosis is limited, patients with incidental liver tumors or lesions with suspicious features in an otherwise healthy liver should be presented at a specialized hepatobiliary unit. Thromboembolism might be an early paraneoplastic symptom and needs to be elucidated further in the context of FL-HCC.
Evaluating the distribution of the locations of colorectal cancer after appendectomy and cholecystectomy
Authors: Ábrahám Szabolcs , Németh Tibor , Benkő Ria , Matuz Mária , Ottlakán Aurél , Váczi Dániel , Paszt Attila , Simonka Zsolt , Lázár György 
Published: May 2020

Abstract
Backgrounds
The number of appendectomies and cholecystectomies performed is gradually increasing worldwide. An increasing incidence of colorectal cancer (CRC) after appendectomy and cholecystectomy has been reported, but the location of tumors in certain segments of the colon and rectum after appendectomy and cholecystectomy is still uncertain. We aimed to evaluate the distribution of the locations of colorectal cancer after appendectomy and/or cholecystectomy in patients who underwent CRC surgery.

Methods
We reviewed the medical records of patients who had undergone CRC surgery between 2015 and 2017 for the presence of previous appendectomy/cholecystectomy. Data were collected from the Colorectal Data Base of the University of Szeged, Department of Surgery.

Results
Surgery for CRC was performed in 640 patients during the study period. Data of 604 patients were analyzed. Appendectomy was performed in 100 patients (16.6%), cholecystectomy in 65 (10.8%), and both interventions in 18 (3%) before the CRC surgery. Out of those patients who underwent appendectomy alone, 92 (92%) had undergone appendectomy more than 10 years before the CRC surgery. Also in these 100 patients, the prevalence of right-sided colon cancer (CC) was 35% (n = 35), in comparison with the prevalence among the 504 other patients (20.4%, n = 103). The prevalence of right-sided CC among patients who underwent cholecystectomy alone was 36.9% (n = 24), in comparison with 21.2% (n = 114) of the 539 other patients.

Conclusions
A significant left to right side shift in CRC was noted among patients who had previously undergone appendectomy/cholecystectomy. Because right-sided CC has a worse prognosis, the role of incidental appendectomy and routine cholecystectomy seems that need re-evaluation.
Neddylation inhibition activates the protective autophagy through NF-κB-catalase-ATF3 Axis in human esophageal cancer cells
Authors: Liang Yupei , Jiang Yanyu , Jin Xing , Chen Ping , Heng Yongqing , Cai Lili , Zhang Wenjuan , Li Lihui , Jia Lijun 
Published: May 2020

Abstract
Background
Protein neddylation plays a tumor-promoting role in esophageal cancer. Our previous study demonstrated that neddylation inhibition induced the accumulation of ATF4 to promote apoptosis in esophageal cancer cells. However, it is completely unknown whether neddylation inhibition could induce autophagy in esophageal cancer cells and affect the expression of other members of ATF/CREB subfamily, such as ATF3.

Methods
The expression of relevant proteins of NF-κB/Catalase/ATF3 pathway after neddylation inhibition was determined by immunoblotting analysis and downregulated by siRNA silencing for mechanistic studies. ROS generation upon MLN4924 treatment was determined by H2-DCFDA staining. The proliferation inhibition induced by MLN4924 was evaluated by ATPLite assay and apoptosis was evaluated by Annexin V /PI double staining.

Results
For the first time, we reported that MLN4924, a specific inhibitor of Nedd8-activating enzyme, promoted the expression of ATF3 to induce autophagy in esophageal cancer. Mechanistically, MLN4924 inhibited the activity of CRLs and induced the accumulation of its substrate IκBα to block NF-κB activation and Catalase expression. As a result, MLN4924 activated ATF3-induced protective autophagy, thereby inhibiting MLN4924-induced apoptosis, which could be alleviated by ATF3 silencing.

Conclusions
In our study, we elucidates a novel mechanism of NF-κB/Catalase/ATF3 pathway in MLN4924-induced protective autophagy in esophageal cancer cells, which provides a sound rationale and molecular basis for combinational anti-ESCC therapy with knockdown ATF3 and neddylation inhibitor (e.g. MLN4924).

Graphical abstract
Autophagy suppression of trophoblast cells induces pregnancy loss by activating decidual NK cytotoxicity and inhibiting trophoblast invasion
Authors: Tan Hai-Xia , Yang Shao-Liang , Li Ming-Qing , Wang Hai-Yan 
Published: May 2020

AbstractBackgroundThe crosstalk between trophoblast cells and decidual NK cells plays an important role in the establishment and maintenance of normal pregnancy. Recent studies reported that autophagy can induce immune tolerance at the maternal fetal interface, while the mechanism remains unclear.MethodsAutophagy levels in the villi of normal and recurrent spontaneous abortion (RSA) patients were detected by transmission electron microscopy. After co-cultured with trophoblast cells pretreated with 3-MA or rapamycin, NK cells were collected and the expression of killer receptors was detected by flow cytometry (FCM). The invasiveness of trophoblasts was tested by Cell invasion assay.ResultsCompared with elective pregnancy termination patients, the level of autophagy in the villi of RSA patients was significantly decreased. Inducing the autophagy level in trophoblast cells with rapamycin could significantly inhibit the cytotoxicity of NK cells in the co-culture system, and supplement of IGF-2 could rectify this effect. Meanwhile, autophagy suppression of trophoblasts reduced the level of Paternally Expressed Gene 10 (PEG10), leading to the impairment of trophoblast cell invasion. In addition, NK cells educated by autophagy-inhibited trophoblasts further decreased the proliferation and invasiveness of trophoblasts. In pregnant mice model, injection with 3-MA promoted the cytotoxicity of uterine NK cells, and increased the embryo absorption rate.ConclusionAutophagy suppression of trophoblasts increase the cytotoxicity of NK cells and damage the trophoblasts invasion possibly by targeting IGF-2 and PEG10, respectively, which ultimately leads to miscarriage.
Soft drink intake is associated with weight gain, regardless of physical activity levels: the health workers cohort study
Authors: González-Morales Romina , Canto-Osorio Francisco , Stern Dalia , Sánchez-Romero Luz María , Torres-Ibarra Leticia , Hernández-López Rubí , Rivera-Paredez Berenice , Vidaña-Pérez Dèsirée , Ramírez-Palacios Paula , Salmerón Jorge , Popkin Barry M. , Barrientos-Gutiérrez Tonatiuh 
Published: May 2020

Abstract
Background
While soft drink intake is positively associated with weight gain, no previous study has investigated whether leisure-time physical activity modifies this association. We estimated the association between soft drink intake and body weight, and explored if this association differed by levels of leisure-time physical activity.

Methods
We used data from the health workers cohort study, a prospective study of Mexican adults (20 to 85y old), including 1268 health workers and their families, who were assessed at baseline (2004–2006) and follow-up (2010–2012). We assessed soft drink intake (cola and flavored soda) using a validated food frequency questionnaire. We measured leisure-time physical activity using a self-report questionnaire, and categorized according to the 2010 World Health Organization (WHO) recommendations. Body weight was measured by trained personnel. The association between changes in soft drink intake and weight change, and if such association varied by levels of physical activity was estimated through fixed-effect models.

Results
An increase in one serving per day of soft drink was associated with 0.10 kg (95% CI 0.00, 0.19) increase in weight per year. This association was not modified by leisure-time physical activity, as demonstrated by the magnitude of the coefficient of the interaction between soft drink, leisure-time physical activity, and time (− 0.03 kg, 95% CI − 0.27 to 0.21); people who complied with the WHO physical activity recommendations gained 0.36 kg/year per serving of soft drink, compared to 0.48 kg/year for people without sufficient physical activity.

Conclusions
Soft drink intake was associated with weight gain. Leisure-time physical activity did not modify the association between soft drink intake and weight gain. This finding challenges the idea that leisure-time physical activity is sufficient to counterbalance weight gain associated to soft drink intake.
The association of MEFV gene mutations with the disease risk and severity of systemic juvenile idiopathic arthritis
Authors: Zhong Linqing , Wang Wei , Li Ji , Ma Mingsheng , Gou Lijuan , Wang Changyan , Yu Zhongxun , Zhang Tiannan , Dong Yanqing , Wei Qijiao , Song Hongmei 
Published: May 2020

Abstract
Background
Systemic juvenile idiopathic arthritis (sJIA) has many clinical features overlapping with familial Mediterranean fever (FMF), which is caused by mutations in MEFV gene. And FMF patients were easily misdiagnosed as sJIA in China. So we speculate that MEFV is critical genetic background for sJIA and influences patients’ severity. In this study, we aim to figure out whether MEFV mutations are risk factor for the occurrence of sJIA and to study the association of MEFV mutations with disease severity of sJIA patients.

Methods
The present study includes 57 sJIA children and 2573 healthy controls. Odd ratio with 95% confidence interval based on allelic frequency of MEFV mutations or variants was used to evaluate their contribution to sJIA susceptibility. Meta-analysis was then performed to reach comprehensive conclusion. All included sJIA patients were grouped by presence and number of MEFV mutations. Clinical data and indicators of disease severity were compared among different groups. Multiple linear regression method was used to find out whether the number of MEFV variants is associated with the severity of sJIA. Kaplan-Meier curves and log rank test were used to estimate the probability of the first relapse.

Results
The MEFV mutations of our subjects predominantly existed in exons 2 and 3. No significant difference was found in allelic frequency between sJIA children and healthy controls. Meta-analysis demonstrated that p.M694V/I was a risk factor for sJIA (pooled OR: 7.13, 95% CI: 3.01–16.89). The relative period of activity was significantly lower in the one mutation group than those with more than one mutation (p = 0.0194). However, no relevance was found in multiple linear regression models.

Conclusions
The mutation p.M694V/I in MEFV might be a risk factor for sJIA. SJIA patients carrying more than one heterozygous mutation in MEFV tend to be more severe than those containing only one, but studies in other cohort of patients need to be performed to validate it.