bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative metabolomic analysis reveals the variations in taxoids and flavonoids among three Taxus species
Authors: Zhou Ting , Luo Xiujun , Zhang Chengchao , Xu Xinyun , Yu Chunna , Jiang Zhifang , Zhang Lei , Yuan Huwei , Zheng Bingsong , Pi Erxu , Shen Chenjia
Published: November 2019

Background

Trees of the genusTaxusare highly valuable medicinal plants with multiple pharmacological effects on various cancer treatments. Paclitaxel fromTaxustrees is an efficient and widely used anticancer drug, however, the accumulation of taxoids and other active ingredients can vary greatly amongTaxusspecies. In our study, the metabolomes of threeTaxusspecies have been investigated.

Results

A total of 2246 metabolites assigned to various primary and secondary metabolic pathways were identified using an untargeted approach. Analysis of differentially accumulated metabolites identified 358 T. media-, 220 T. cuspidata-, and 169 T. mairei-specific accumulated metabolites, respectively. By searching the metabolite pool, 7 MEP pathway precursors, 11 intermediates, side chain products and derivatives of paclitaxel, and paclitaxel itself were detected. Most precursors, initiated intermediates were highly accumulated inT. mairei, and most intermediate products approaching the end point of taxol biosynthesis pathway were primarily accumulated inT. cuspidataandT. media. Our data suggested that there were higher-efficiency pathways to paclitaxel inT. cuspidataandT. mediacompared with inT. mairei. As an important class of active ingredients inTaxustrees, a majority of flavonoids were predominantly accumulated inT. maireirather thanT. mediaandT. cuspidata. The variations in several selected taxoids and flavonoids were confirmed using a targeted approach.

Conclusions

Systematic correlativity analysis identifies a number of metabolites associated with paclitaxel biosynthesis, suggesting a potential negative correlation between flavonoid metabolism and taxoid accumulation. Investigation of the variations in taxoids and other active ingredients will provide us with a deeper understanding of the interspecific differential accumulation of taxoids and an opportunity to accelerate the highest-yielding species breeding and resource utilization.
An application of RASER technique in the treatment of chronic total occlusion accompanied with stent fracture in right coronary artery: a case report
Authors: Xue Yajun , Zhou Boda , Wang Weimin , Miao Guobin , Zhang Ou , Zhou Jie , Geng Yu , Zhai Yanlong , Ren Chunhui , Zhang Ping
Published: November 2019

Background

The interventional treatment of chronic total occlusion (CTO) with stent fracture as well as severe calcification was extremely difficult and no effective technique has been reported.

Case presentation

A 50-year-old woman was hospitalized for angina, angiography revealed triple vessel disease, CTO accompanied with stent fracture in right coronary artery (RCA). Treatment using conventional coronary intervention was expected to be difficult. Therefore, we performed RASER technique, which was a combination of excimer laser coronary atherectomy (ELCA) with rotational atherectomy (RA), followed by the deployment of drug-eluting stents. Intravascular ultrasound (IVUS) revealed well attachment of the stents, the patient was discharged 3 days after the procedure and no recurrent chest discomfort was reported in a follow-up time of 10 months.

Conclusion

This case report provided a first report of RASER technique in the treatment of CTO with stent fracture and severe calcification.
Topoisomerase I activity and sensitivity to camptothecin in breast cancer-derived cells: a comparative study
Authors: Tesauro Cinzia , Simonsen Anne Katrine , Andersen Marie Bech , Petersen Kamilla Wandsoe , Kristoffersen Emil Laust , Algreen Line , Hansen Noriko Yokoyama , Andersen Anne Bech , Jakobsen Ann Katrine , Stougaard Magnus , Gromov Pavel , Knudsen Birgitta R. , Gromova Irina
Published: November 2019

Background

Camptothecin (CPT) and its derivatives are currently used as second- or third-line treatment for patients with endocrine-resistant breast cancer (BC). These drugs convert nuclear enzyme DNA topoisomerase I (TOP1) to a cell poison with the potential to damage DNA by increasing the half-life of TOP1-DNA cleavage complexes (TOP1cc), ultimately resulting in cell death. In small and non-randomized trials for BC, researchers have observed extensive variation in CPT response rates, ranging from 14 to 64%. This variability may be due to the absence of reliable selective parameters for patient stratification. BC cell lines may serve as feasible models for generation of functional criteria that may be used to predict drug sensitivity for patient stratification and, thus, lead to more appropriate applications of CPT in clinical trials. However, no study published to date has included a comparison of multiple relevant parameters and CPT response across cell lines corresponding to specific BC subtypes.

Method

We evaluated the levels and possible associations of seven parameters including the status of theTOP1gene (i.e. amplification), TOP1 protein expression level, TOP1 activity and CPT susceptibility, activity of the tyrosyl-DNA phosphodiesterase 1 (TDP1), the cellular CPT response and the cellular growth rate across a representative panel of BC cell lines, which exemplifies three major BC subtypes: Luminal, HER2 and TNBC.

Results

In all BC cell lines analyzed (without regard to subtype classification), we observed a significant overall correlation between growth rate and CPT response. In cell lines derived from Luminal and HER2 subtypes, we observed a correlation betweenTOP1gene copy number, TOP1 activity, and CPT response, although the data were too limited for statistical analyses. In cell lines representing Luminal and TNBC subtypes, we observed a direct correlation between TOP1 protein abundancy and levels of enzymatic activity. In all three subtypes (Luminal, HER2, and TNBC), TOP1 exhibits approximately the same susceptibility to CPT. Of the three subtypes examined, the TNBC-like cell lines exhibited the highest CPT sensitivity and were characterized by the fastest growth rate. This indicates that breast tumors belonging to the TNBC subtype, may benefit from treatment with CPT derivatives.

Conclusion

TOP1 activity is not a marker for CPT sensitivity in breast cancer.
Expression of FSCN1 and FOXM1 are associated with poor prognosis of adrenocortical carcinoma patients
Authors: Liang Jiayu , Liu Zhihong , Wei Xin , Zhou Liang , Tang Yongquan , Zhou Chuan , Wu Kan , Zhang Fuxun , Zhang Fan , Lu Yiping , Zhu Yuchun
Published: November 2019

Background

Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumour. Due to a high tumour recurrence rate, the post-operative overall survival (OS) and disease-free survival (DFS) of ACCs is limited. Our research aims to identify the role of the epithelial-mesenchymal transition (EMT) related genes FSCN1 and FOXM1 in the tumour microenvironment and assess their prognostic value in ACCs.

Methods

Clinical and specimen data from 130 adrenocortical carcinoma (ACC) patients was acquired from the Cancer Genome Atlas (TCGA) database (n = 79) and a West China Hospital (WCH) cohort (n = 51). In the WCH cohort, archived formalin-fixed paraffin embedded (FFPE) samples were collected for immunohistochemical analysis. The correlation between the EMT genes and the tumour microenvironment status was estimated based on the Tumour Immune Estimation Resource (TIMER) algorithm. Kaplan-Meier analysis, followed by univariate and multivariate regression analyses, were performed to identify the prognostic association of FSCN1 and FOXM1.

Results

FSCN1 and FOXM1 were over-expressed in ACC tissue when compared with adrenocortical adenoma and normal adrenal tissue. Over-expression of FSCN1 or FOXM1 was associated with the tumour microenvironment and immune signatures in ACCs. Patients with higher expression of FSCN1 or FOXM1 were more likely to have worse prognoses. The prognostic effects were further verified in both early (stage I/II) and advanced (stage III/IV) ACCs. Furthermore, FSCN1 and FOXM1 appeared as independent prognostic factors in ACC.

Conclusions

These results show that FSCN1 and FOXM1 are independent prognostic factors in ACCs and over-expression of FSCN1 or FOXM1 indicates a worse prognosis.
Vocal and motor behaviors as a possible expression of gastrointestinal problems in preschoolers with Autism Spectrum Disorder
Authors: Prosperi Margherita , Santocchi Elisa , Muratori Filippo , Narducci Chiara , Calderoni Sara , Tancredi Raffaella , Morales Maria Aurora , Guiducci Letizia
Published: November 2019

Background

Gastrointestinal (GI) problems are one of the most frequent comorbidities in Autism Spectrum Disorder (ASD) but can be under-recognized due to the concomitant communication difficulties of this population. Accordingly, some associated behaviors (AB) such as verbal and motor behaviors (VB and MB, respectively) have been identified as a possible expression of an underlying GI problem and evaluated through an ad hoc questionnaire (the Associated Behaviors Questionnaire -ABQ-). The aims of this study were to investigate the presence and the type of AB in an Italian sample of ASD preschoolers, and to determine their correlations with GI problems.

Methods

We included 85 ASD preschoolers (mean age 4.14 years; SD 1.08) splitted into two groups (GI and No-GI) through the GI Severity Index instrument. AB were evaluated through the ABQ that includes VB, MB and Changes in overall state (C) clusters. Specific tools were administered to evaluate the ASD core ad associated symptoms, as well as the intellective and adaptive functioning.

Results

The GI group (N = 30) showed significantly higher scores in all the three ABQ areas (VB, MB and C) than the No-GI group (N = 55), with a positive correlation between GI symptoms and some specific AB as well as ABQ Total score. By dividing the whole sample in verbal and non-verbal individuals, both specific and shared AB emerged in the two groups.

Conclusions

Our results alert clinicians to consider behavioral manifestations as a possible expression of GI problems in ASD subjects. Therefore, the evaluation of AB may be useful to identify the presence of GI problems in the ASD populations, and especially in non-verbal ASD children.
Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial
Authors: Smith-Apeldoorn Sanne Y. , Veraart Jolien K. E. , Kamphuis Jeanine , van Asselt Antoinette D. I. , Touw Daan J. , aan het Rot Marije , Schoevers Robert A.
Published: November 2019

Background

There is an urgent need to develop additional treatment strategies for patients with treatment-resistant depression (TRD). The rapid but short-lived antidepressant effects of intravenous (IV) ketamine as a racemic mixture have been shown repeatedly in this population, but there is still a paucity of data on the efficacy and safety of (a) different routes of administration, and (b) ketamine’s enantiomers esketamine and arketamine. Given practical advantages of oral over IV administration and pharmacodynamic arguments for better antidepressant efficacy of esketamine over arketamine, we designed a study to investigate repeated administration of oral esketamine in patients with TRD.

Methods

This study features a triple-blind randomized placebo-controlled trial (RCT) comparing daily oral esketamine versus placebo as add-on to regular antidepressant medications for a period of 6 weeks, succeeded by a follow-up of 4 weeks. The methods support examination of the efficacy, safety, tolerability, mechanisms of action, and economic impact of oral esketamine in patients with TRD.

Discussion

This is the first RCT investigating repeated oral esketamine administration in patients with TRD. If shown to be effective and tolerated, oral esketamine administration poses important advantages over IV administration.

Trial registration

Dutch Trial Register, NTR6161. Registered 21 October 2016.
Peer support for frequent users of inpatient mental health care in Uganda: protocol of a quasi-experimental study
Authors: Ryan Grace K. , Kamuhiirwa Mauricia , Mugisha James , Baillie Dave , Hall Cerdic , Newman Carter , Nkurunungi Eddie , Rathod Sujit D. , Devries Karen M. , De Silva Mary J. , Mpango Richard
Published: November 2019

Background

Reducing readmissions among frequent users of psychiatric inpatient care could result in substantial cost savings to under-resourced mental health systems. Studies from high-income countries indicate that formal peer support can be an effective intervention for the reduction of readmissions among frequent users. Although in recent years formal peer support programmes have been established in mental health services in a few low- and middle-income countries (LMICs), they have not been rigorously evaluated.

Methods

This protocol describes a quasi-experimental difference-in-differences study conducted as part of a broader evaluation of the Brain Gain II peer support programme based at Butabika National Referral Hospital in Kampala, Uganda. The primary objective is to investigate whether frequent users of psychiatric inpatient care who have access to a peer support worker (PSW+) experience a greater reduction in rehospitalisation rates and number of days spent in hospital compared to those who do not have access to a peer support worker (PSW-). Frequent users, defined as adults diagnosed with either a mental disorder or epilepsy who have had three or more inpatient stays at Butabika over the previous 24 months, are referred to Brain Gain II by hospital staff on five inpatient wards. Frequent users who normally reside in a district where peer support workers currently operate (Kampala, Jinja, Wakiso and Mukono) are eligible for formal peer support and enter the PSW+ group. Participants in the PSW+ group are expected to receive at least one inpatient visit by a trained peer support worker before hospital discharge and three to six additional visits after discharge. Frequent users from other districts enter the PSW- group and receive standard care. Participants’ admissions data are extracted from hospital records at point of referral and six months following referral.

Discussion

To the best of our knowledge, this will be the first quasi-experimental study of formal peer support in a LMIC and the first to assess change in readmissions, an outcome of particular relevance to policy-makers seeking cost-effective alternatives to institutionalised mental health care.
Spatial quantile regression with application to high and low child birth weight in Malawi
Authors: Ngwira Alfred
Published: November 2019

Background

Child low and high birth weight are important public health problems. Many studies have looked at factors of low and high birth weight using mean regression. This study aimed at using quantile regression to find out determinants of low and high birth weight.

Methods

Spatial quantile regression models at 0.05 and 0.95 percentiles of birth weight were fitted to 13,087 children birth weight in kilograms using Malawi demographic health survey data of 2010 study. Full Bayesian method by integrated nested Laplace approximations (INLA) was used to estimate the model. Second order random walk priors were assigned for mother age and antenatal visits for pregnancy while Gaussian markov random field prior was used for district of the child.

Results

Residual spatial patterns reveal areas in the southern region promoting high birth weight while areas in the central and northern region promote low birth weight. Most fixed effects findings are consistent with the literature. Richest family, normal mother body mass index (BMI), mother over weight (BMI > 25 kg/m2), birth order 2–3, mother secondary education and height (≥150 cm) negate low birth weight while weight 45–70 kg promote low birth weight. Birth order category 6+, mother height (≥150 cm) and poor wealth quintile, promote high birth weight, while richer and richest wealth quintiles and education categories: primary, secondary, and higher, and mother overweight (BMI > 25 kg/m2) reduce high birth weight. Antenatal visits for pregnancy reduce both low and high birth weight.

Conclusion

Strategies to reduce low and high birth weight should simultaneously address mother education, weight gain during pregnancy and poverty while targeting areas increasing low and high birth weight.
A mixed-methods evaluation of community-based healthy kitchens as social enterprises for refugee women
Authors: Sahyoun Nadine R. , Jamaluddine Zeina , Choufani Jowel , Mesmar Sandra , Reese-Masterson Amelia , Ghattas Hala
Published: November 2019

Background

The aim of this study is to investigate the potential impact of a community-based intervention - the Healthy Kitchens, Healthy Children (HKHC) intervention - on participating women’s household’s economics and food security status, decision making, mental health and social support.

Methods

We established two healthy kitchens in existing community-based organizations in Palestinian camps in Lebanon. These were set up as small business enterprises, using participatory approaches to develop recipes and train women in food preparation, food safety and entrepreneurship. We used a mixed-methods approach to assess the impact of participating in the program on women’s economic, food security, decision making, social and mental health outcomes. A questionnaire was administered to women at baseline and at an 8-month endpoint. The end line survey was complemented by a set of embedded open-ended questions.

Results

Thirty-two Palestinian refugee women were employed within the kitchens on a rotating basis. Participating women had a 13% increase in household expenditure. This was translated into a significant increase in food (p < 0.05) and clothing expenditures (p < 0.01), as well as a reduction in food insecurity score (p < 0.01). These findings were supported by qualitative data which found that the kitchens provided women with financial support in addition to a space to form social bonds, discuss personal issues and share experiences.

Conclusions

This model created a social enterprise using the concept of community kitchens linked to schools and allowed women to significantly contribute to household expenditure and improve their food security.
Knowledge and menstrual hygiene practice among adolescent school girls in southern Ethiopia: a cross-sectional study
Authors: Belayneh Zelalem , Mekuriaw Birhanie
Published: November 2019

Background

Menstruation is a normal physiological process of females at their reproductive age. However, it is surrounded with social taboos and supernatural beliefs. The poor knowledge and understanding of menstruation may lead to unsafe hygienic practice that intern increases the risk of reproductive and genito-urinary tract infections, cervical cancer, school drop-out, poor academic performance and overall poor quality of life. Despite such clinical and academic effects, the knowledge and hygienic practice of adolescent girls towards menstruation is not well addressed in Ethiopia, particularly among school adolescent girls. Therefore, the main objective of this study was to assess the knowledge and menstrual hygiene practice among adolescent school girls in southern Ethiopia.

Methods

This was an institutional based cross-sectional study conducted at Gedeo zone high schools among 791 randomly selected adolescent girls using multi stage sampling technique. Data were collected using interviewer administered questionnaire. The collected data were entered to EPI-INFO (soft ware) and exported to SPSS version 20 for analysis. Bivariable and multivariable logistics analyses were computed to identify factors associated with the poor menstrual hygienic practice. During bi-variable analysis, variables with P-values of less than 0.25 were entered to multivariable model for further analysis. In the final model, P-value of less than 0.05 was used as a base to identify factors having a statistically significant association with poor menstrual hygiene practice at corresponding 95% confidence interval.

Result

From a total of 791 adolescent girls participated in this study, 68.3% had poor knowledge of menstruation. About 48.1% of school girls used absorbent materials, and 69.5% clean their external genitalia. Generally, 60.3% of girls had poor menstrual hygienic practice. Age less than 15 years [OR = 1.71:95% CI (1.22, 2.39)], longer days of menstrual flow [OR = 2.51:95% CI (1.66, 3.80)] and poor knowledge of menses [OR = 1.48:95% CI (1.04, 2.1)] had a significantly associated with poor menstrual hygiene practice.

Conclusion

Majority of adolescent school girls had poor knowledge regarding menstruation and their hygienic practices are incorrect. This demonstrates a need to design acceptable awareness creation and advocacy programs to improve the knowledge and promote safe hygienic practice of adolescent school girls during menstruation.
Association between dietary acid load and the risk of hypertension among adults from South China: result from nutrition and health survey (2015–2017)
Authors: Chen Shao-wei , Ji Gui-yuan , Jiang Qi , Wang Ping , Huang Rui , Ma Wen-jun , Chen Zi-hui , Peng Jie-wen
Published: November 2019

Background

Higher dietary acid load (DAL) was considered to be associated with an elevated risk of hypertension, while related data from mainland China remains scarce and incomplete. We aim to evaluate the association between DAL and the risk of hypertension among adults from South China.

Methods

We conducted a nutrition and health survey in Guangdong Province located in southern China from 2015 to 2017. A four-stage probability sampling method was utilized to select representative samples of citizens aged ≥18 years old. DAL was assessed by potential renal acid load (PRAL) and net endogenous acid production (NEAP). Participants were divided to 4 groups (Q1-Q4) according to the quartile points of PRAL or NEAP distributions. Generalized linear mixed effects models were applied to evaluate the association between DAL and the risk of hypertension.

Results

A total of 3501 individuals were eligible for this study and 45.9% was male participants. Hypertension rate was 30.7%. A higher PRAL was associated with higher prevalence rate of hypertension among the male (P-trend = 0.03). OR for Q2 was 1.34 (95%CI, 0.94–1.91), Q3 was 1.53 (95%CI = 1.08, 2.16) and Q4 was 1.51 (95%CI, 1.08–2.16) among the male. However, as for total participants, the female, the participants with ≤55 years or participants with > 55 years, the associations were lack of significance. With respect to association between NEAP and hypertension, non-significant results were identified.

Conclusions

The current study indicated male hypertension was associated with higher PRAL, while given to this study was cross-sectional design, further studies are warranted to verify the association.
Early-stage T1b adenocarcinoma arising in the remnant cystic duct after laparoscopic cholecystectomy: a case report and literature review
Authors: Prasoon Pankaj , Hirose Yuki , Sakata Jun , Yuza Kizuki , Moro Kazuki , Toge Koji , Miura Kohei , Nagahashi Masayuki , Kobayashi Takashi , Nihei Kouei , Nakamura Atsuo , Wakai Toshifumi
Published: November 2019

Background

The cystic duct has been included in the staging classification scheme for gallbladder cancer since the 2010 publication of the AJCC Cancer Staging Manual (7th edition). To our knowledge, only seven other cases of adenocarcinoma arising in the remnant cystic duct following cholecystectomy have been reported in the English-language literature, and none has been reported as primary early-stage T1b remnant cystic duct cancer (CDC). We report, herein, a case of primary adenocarcinoma arising in the remnant cystic duct in a patient with history of laparoscopic cholecystectomy for gallstone disease.

Case presentation

An 81-year-old female presented with abdominal pain. Her medical history included a laparoscopic cholecystectomy for cholecystolithiasis two years prior. Jaundice was observed; imaging studies suggested that this was caused by choledocholithiasis. Blood chemistry findings showed severe liver dysfunction. Endoscopic retrograde cholangiography revealed haemobilia from the common bile duct with no evidence of choledocholithiasis. A bile sample showed Papanicolaou class IV cytology. As the extent of tumour spread was undetermined by abdominal ultrasonography and endoscopic ultrasonography, peroral cholangioscopy (POCS) was performed, which revealed tiny papillary lesions within the confluence of cystic duct, and fine granular lesions in the centre of bile ducts, signifying early-stage remnant CDC. Extrahepatic bile duct resection with regional lymphadenectomy was done. Histopathological findings revealed a 42-mm tubular adenocarcinoma originating from the remnant cystic duct with the considerable shallow spread across the extrahepatic bile ducts. It invaded the fibromuscular layer, with no lymphovascular or perineural invasion, no lymph node metastasis (13 nodes examined), and uninvolved surgical resection margin (R0 resection), and was staged as pT1bN0M0, Stage I.

Conclusions

Primary early-stage T1b remnant CDC is an uncommon condition for which early diagnosis is challenging; if intraoperatively recognized, it can complicate surgery. Our experience of this case and an overview of the English literature suggest that POCS is an efficient tool to diagnosis this tumour and assess its spread along the extrahepatic bile ducts.
Clinically significant Prostate Cancer diagnosed using a urinary molecular biomarker-based risk score: two case reports
Authors: Minnee Pieter , Hessels Daphne , Schalken Jack A. , Van Criekinge Wim
Published: November 2019

Background

Identifying men for a repeat prostate biopsy is a conundrum to urologists. Risk calculators (RCs) such as the European Randomized Study of Screening for Prostate Cancer (ERSPC) RCs have been developed to predict the outcome of prostate biopsies and have been shown to improve diagnostic accuracy compared to PSA alone. However, it was recently shown that the outcome for high-grade prostate cancer (PCa) upon biopsy tended to be underestimated in men with previous negative biopsies using ERSPC RC model 4. For these men, an individualized approach combining the clinical information with the outcome of biomarker-related urine tests may help to make a more informed decision.

Case presentation

Two men, aged 66 and 69 respectively when presented in the clinic, show the typical dilemma of urologist and patient for electing repeat prostate biopsy. Both men had normal DRE findings, did not have a family history of PCa, presented with serum PSA values between 3 and 10 ng/ml and the first biopsies were negative for disease. The ERSPC RC4 did not indicate a biopsy in these men. The urinary molecular biomarker-based test for HOXC6 and DLX1, combining biomarker-expression profiling with clinical risk factors, resulted in SelectMDx Risk scores for these men that were higher than the cut-off of the test. Based on this outcome, mpMRI was performed with an outcome of PI-RADS ≥4 in both men. Histopathological evaluation of TRUS-guided biopsies confirmed high-grade PCa.

Conclusions

The urinary molecular biomarker-based risk score played a pivotal role in the diagnosis of clinically significant PCa whereas ERSPC RC4 outcome would not have indicated further diagnostic follow-up in these two cases. The timely diagnosis was shown to be crucial for the curative treatment by radical retropubic prostatectomy and the potential life-years gained for these two vital males.
Realizing better doctor-patient dialogue about choices in palliative care and early phase clinical trial participation: towards an online value clarification tool (OnVaCT)
Authors: van Lent Liza G. G. , Stoel Nicole K. , van Weert Julia C. M. , van Gurp Jelle , de Jonge Maja J. A. , Lolkema Martijn P. , Gort Eelke H. , Pulleman Saskia M. , Oomen-de Hoop Esther , Hasselaar Jeroen , van der Rijt Carin C. D.
Published: November 2019

Background

Patients with advanced cancer for whom standard systemic treatment is no longer available may be offered participation in early phase clinical trials. In the decision making process, both medical-technical information and patient values and preferences are important. Since patients report decisional conflict after deciding on participation in these trials, improving the decision making process is essential. We aim to develop and evaluate an Online Value Clarification Tool (OnVaCT) to assist patients in clarifying their values around this end-of-life decision. This improved sharing of values is hypothesized to support medical oncologists in tailoring their information to individual patients’ needs and, consequently, to support patients in taking decisions in line with their values and reduce decisional conflict.

Methods

In the first part, patients’ values and preferences and medical oncologists’ views hereupon will be explored in interviews and focus groups to build a first prototype OnVaCT using digital communication (serious gaming). Next, we will test feasibility during think aloud sessions, to deliver a ready-to-implement OnVaCT. In the second part, the OnVaCT, with accompanied training module, will be evaluated in a pre-test (12–18 months before implementation) post-test (12–18 months after implementation) study in three major Dutch cancer centres. We will include 276 patients (> 18 years) with advanced cancer for whom standard systemic therapy is no longer available, and who are referred for participation in early phase clinical trials. The first consultation will be recorded to analyse patient-physician communication regarding the discussion of patients’ values and the decision making process. Three weeks afterwards, decisional conflict will be measured.

Discussion

This project aims to support the discussion of patient values when considering participation in early phase clinical trials. By including patients before their first appointment with the medical oncologist and recording that consultation, we are able to link decisional conflict to the decision making process, e.g. the communication during consultation. The study faces challenges such as timely including patients within the short period between referral and first consultation. Furthermore, with new treatments being developed rapidly, molecular stratification may affect the patient populations included in the pre-test and post-test periods.

Trial registration

Netherlands Trial Registry number: NTR7551 (prospective; July 17, 2018).
Nocturnal finger skin temperature in menstrual cycle tracking: ambulatory pilot study using a wearable Oura ring
Authors: Maijala Anna , Kinnunen Hannu , Koskimäki Heli , Jämsä Timo , Kangas Maarit
Published: November 2019

Background

Body temperature is a common method in menstrual cycle phase tracking because of its biphasic form. In ambulatory studies, different skin temperatures have proven to follow a similar pattern. The aim of this pilot study was to assess the applicability of nocturnal finger skin temperature based on a wearable Oura ring to monitor menstrual cycle and predict menstruations and ovulations in real life.

Methods

Volunteer women (n = 22) wore the Oura ring, measured ovulation through urine tests, and kept diaries on menstruations at an average of 114.7 days (SD 20.6), of which oral temperature was measured immediately after wake-up at an average of 1.9 cycles (SD 1.2). Skin and oral temperatures were compared by assessing daily values using repeated measures correlation and phase mean values and differences between phases using dependent t-test. Developed algorithms using skin temperature were tested to predict the start of menstruation and ovulation. The performance of algorithms was assessed with sensitivity and positive predictive values (true positive defined with different windows around the reported day).

Results

Nocturnal skin temperatures and oral temperatures differed between follicular and luteal phases with higher temperatures in the luteal phase, with a difference of 0.30 °C (SD 0.12) for skin and 0.23 °C (SD 0.09) for oral temperature (p < 0.001). Correlation between skin and oral temperatures was found using daily temperatures (r = 0.563, p < 0.001) and differences between phases (r = 0.589, p = 0.004). Menstruations were detected with a sensitivity of 71.9–86.5% in window lengths of ±2 to ±4 days. Ovulations were detected with the best-performing algorithm with a sensitivity of 83.3% in fertile window from − 3 to + 2 days around the verified ovulation. Positive predictive values had similar percentages to those of sensitivities. The mean offset for estimations were 0.4 days (SD 1.8) for menstruations and 0.6 days (SD 1.5) for ovulations with the best-performing algorithm.

Conclusions

Nocturnal skin temperature based on wearable ring showed potential for menstrual cycle monitoring in real life conditions.
Use of traditional and complementary medicine among Norwegian cancer patients in the seventh survey of the Tromsø study
Authors: Kristoffersen Agnete Egilsdatter , Stub Trine , Broderstad Ann Ragnhild , Hansen Anne Helen
Published: November 2019

Background

Traditional and complementary medicine (T&CM) is commonly used by cancer patients in Northern Norway, in particular spiritual forms like traditional healing. T&CM is mainly used complementary to conventional cancer treatment and is rarely discussed with conventional health care providers, increasing the risk of negative interaction with conventional cancer care. The aim of this study was to investigate the use of T&CM among cancer patients in Tromsø, and to investigate the differences in T&CM use between people living with cancer, people with cancer previously, and people without a history of cancer.

Method

Data was drawn from the seventh survey of the Tromsø study conducted in 2015–2016. All inhabitants of Tromsø aged 40 and above were invited to participate (n = 32,591) of whom n = 21,083 accepted the invitation (response rate 65%). Data was collected thorough three self-administered questionnaires and a comprehensive clinical examination. Pearson chi-square tests, Fisher exact tests and one-way ANOVA tests were used to describe differences between the groups while binary logistic regressions were used for adjusted values.

Results

Eight percent of the participants (n = 1636) reported to have (n = 404) or have had (n = 1232) cancer. Of the participants with cancer at present 33.4% reported use of T&CM within the last year, 13.6% had consulted a T&CM provider, 17.9% had used herbal medicine/natural remedies and 6.4% had practiced self-help techniques. The participants with cancer at present were more likely to have visited a T&CM provider than participants with cancer previously (13.6% vs. 8.7%, p = 0.020). Among the participants with cancer at present, 6.4% reported to have consulted a TM provider, 5.8% had consulted an acupuncturist, while 4.7% had consulted other CM providers. Women were significantly more likely than men to have used acupuncture and self-help techniques. No significant gender differences were found regarding visits to other CM providers, TM providers nor use of herbal medicine/natural remedies.

Conclusion

The findings are in line with previous research suggesting that both men and women use TM complementary to other CM modalities outside the official health care system. As herbal medicine might interact with conventional cancer treatment, health care providers need to discuss such use with their patients.
Preparing competent graduates for delivering pharmaceutical care: an experience from Northern Cyprus
Authors: Abdi Abdikarim Mohamed , Meštrović Arijana , Demirdamar Rumeysa , Basgut Bilgen
Published: November 2019

Background

This paper describes the implementation and evaluation of a clinical pharmacy practice (CPP) course in Northern Cyprus. The course covered a range of subjects, including internal medicine, cardiovascular and respiratory diseases, and drug information services.

Methods

An 8-week structured CPP course was designed for fifth-year students. Students’ competencies were assessed using an objective structural clinical examination (OSCE) before and after the intervention. The course addressed all CPP competence domains and learning outcomes, and it utilized a wide variety of learning activities. Student perceptions, experience and preceptor evaluations were assessed using surveys.

Results

Students reported that the learning objectives of the course were met. Substantial knowledge and skills in different areas of CPP were gained. A significant overall enhancement in the average grades on the OSCE was identified (23.09 ± 0.75 and 27.51 ± 0.71 out of 40). Students received the highest scores in drug information data retrieval and interpretation (4.4 ± 0.13), communication skills (4.2 ± 0.09) and public health promotion (3.92 ± 0.12). The lowest scores were recorded in clinical prescription management problems (2.5 ± 0.23) and pharmacotherapy application (2.54 ± 0.18).

Conclusion

Students’ scores significantly improved from the baseline in the core competence domains. Most students found the structure, process and outcomes of the course to be beneficial and satisfactory.
Dementia assessment and management in primary care settings: a survey of current provider practices in the United States
Authors: Bernstein Alissa , Rogers Kirsten M. , Possin Katherine L. , Steele Natasha Z.R. , Ritchie Christine S. , Kramer Joel H. , Geschwind Michael , Higgins Joseph J. , Wohlgemuth Jay , Pesano Rick , Miller Bruce L. , Rankin Katherine P.
Published: November 2019

Background

Primary care providers (PCPs) are typically the first to screen and evaluate patients for neurocognitive disorders (NCDs), including mild cognitive impairment and dementia. However, data on PCP attitudes and evaluation and management practices are sparse. Our objective was to quantify perspectives and behaviors of PCPs and neurologists with respect to NCD evaluation and management.

Methods

A cross-sectional survey with 150 PCPs and 50 neurologists in the United States who evaluated more than 10 patients over age 55 per month. The 51-item survey assessed clinical practice characteristics, and confidence, perceived barriers, and typical practices when diagnosing and managing patients with NCDs.

Results

PCPs and neurologists reported similar confidence and approaches to general medical care and laboratory testing. Though over half of PCPs performed cognitive screening or referred patients for cognitive testing in over 50% of their patients, only 20% reported high confidence in interpreting results of cognitive tests. PCPs were more likely to order CT scans than MRIs, and only 14% of PCPs reported high confidence interpreting brain imaging findings, compared to 70% of specialists. Only 21% of PCPs were highly confident that they correctly recognized when a patient had an NCD, and only 13% were highly confident in making a specific NCD diagnosis (compared to 72 and 44% for neurologists, bothp < 0.001). A quarter of all providers identified lack of familiarity with diagnostic criteria for NCD syndromes as a barrier to clinical practice.

Conclusions

This study demonstrates how PCPs approach diagnosis and management of patients with NCDs, and identified areas for improvement in regards to cognitive testing and neuroimaging. This study also identified all providers’ lack of familiarity with published diagnostic criteria for NCD syndromes. These findings may inform the development of new policies and interventions to help providers improve the efficacy of their decision processes and deliver better quality care to patients with NCDs.
Correction to: c-Src confers resistance to mitotic stress through inhibition of DMAP1/Bub3 complex formation in pancreatic cancer
Authors: Li Jingjie , Hu Bin , Wang Ting , Huang Wenhua , Ma Chunmin , Zhao Qin , Zhuo Lingang , Zhang Tao , Jiang Yuhui
Published: November 2019

Following publication of the work [1], authors reported the “flow cytometery plots” panel in Fig. 4e contained an inter-duplication in error.
GnRH agonists to sustain the luteal phase in antagonist IVF cycles: a randomized prospective trial
Authors: Fusi Francesco M. , Brigante Claudio M. , Zanga Laura , Mignini Renzini Mario , Bosisio Chiara , Fadini Rubens
Published: November 2019

Background

The addition of a GnRH analogue to the luteal phase in in vitro fertilization programs has been seldom proposed due to the presence of GnRH receptors in the endometrium. The aim of the study was to evaluate the effect of triptorelin addition in short antagonist cycles, compared to cycles where the only supplementation was progesterone.

Methods

The primary objective of this study was the study of the effect of Triptorelin addiction during the luteal phase on the live birth rate. Secondary objectives of efficacy were pregnancy rates and implantation rates, as well as safety in terms of OHSS risks. The study was a prospective, randomized, open study, performed in two independent Centers from July 2013 to October 2015. Patients were divided into three groups: a) Regular antagonist protocol, with only luteal progesterone; b) Antagonist protocol with luteal triptorelin as multiple injections, c) Antagonist protocol with luteal triptorelin as single bolus. Descriptive statistics were obtained for all the parameters. Mean and standard deviation were used for all quantitative parameters. Differences between percentages were studied using Chi-square test generalized to the comparison of several proportions.

Results

A total number of 1344 patients completed the study, 786 under the age of 35 years, and 558 over 35 years. It was observed an increase of positive HCG results, Clinical pregnancy rates and Delivery rates when triptorelin was added in the luteal phase, irrespective whether as a single bolus or five injections. This increase was statistically significant both for pregnancy rates and delivery rates. The statistic difference between pregnancies and deliveries obtained with or without luteal triptorelin reachedp < 0,01. No increase of OHSS risk was observed.

Conclusions

From this large study it appears that the concept of luteal phase supplementation should be revisited. From our study it appears that triptorelin addition to the luteal phase of antagonist cycles, either as a single bolus or using multiple injections, is a good tool to optimize ART results.

Trial registration

The study was approved by the Ethics Committee of Provincia di Bergamo (n 1203/2013).
Type of screen time moderates effects on outcomes in 4013 children: evidence from the Longitudinal Study of Australian Children
Authors: Sanders Taren , Parker Philip D. , del Pozo-Cruz Borja , Noetel Michael , Lonsdale Chris
Published: November 2019

Background

Excessive engagement with digital screens is harmful to children’s health. However, new evidence suggests that exposure at moderate levels may not be harmful and may even provide benefit. Therefore, our objective was to determine if there are curvilinear relationships between different types of screen time and a diverse set of outcomes, including health and education.

Methods

We address our objective using a repeated measures design. Children (N = 4013), initially aged 10–11 were assessed every 2 years between 2010 and 2014. Children’s screen time behavior was measured using time-use diaries, and categorized into five types: social, passive, interactive, educational, or other. We used measures of children’s physical health, health-related quality of life, socio-emotional outcomes, and school achievement. The analysis plan was pre-registered. Models were adjusted for gender, socio-economic status, ethnicity, number of siblings, and housing factors.

Results

There were linear associations between total screen time and all outcomes, such that more screen time was associated with worse outcomes. However, there was variability when examined by screen time type. Passive screen time (e.g., TV) was associated with worse outcomes, educational screen time (e.g., computer for homework) was associated with positive educational outcomes and had no negative relations with other outcomes. Interactive screen time (e.g., video games) had positive associations with educational outcomes but negative associations with other outcomes. In all instances, these significant associations were small or very small, with standardised effects < 0.07. We found little evidence of curvilinear relationships.

Conclusions

The small effects of screen time on children’s outcomes appear to be moderated by the type of screen time. Policy makers, educators, and parents should consider the type of screen time when considering the benefits and harms of use.
Diverse school community engagement with the North Carolina active routes to school project: a diffusion study
Authors: LaJeunesse Seth , Thompson Sam , Pullen-Seufert Nancy , Kolbe Mary Bea , Heiny Stephen , Thomas Cathy , Johnson Edward R.
Published: November 2019

Background

Schools located in rural parts of the United States and North Carolina have benefited proportionally less from the federal Safe Routes to School (SRTS) program than their more urban counterparts. We investigated whether and how diverse elementary and middle school communities throughout North Carolina have engaged in a SRTS-inspired, multi-sectoral initiative called the Active Routes to School (ARTS) project over the course of 5 years (2013 through 2017).

Methods

Analyses included a study sample of 2602 elementary and middle schools in North Carolina, 853 that participated in the ARTS project over the five-year study period and 1749 that had not. Statistical models controlling for county- and school-level confounders predicted schools’ involvement in walking and bicycling-promotive events, programs, and policies over time.

Results

Schools’ engagement with ARTS Project programming increased significantly over the study period, with 33% of eligible schools participating with the project by the end of 2017. Participation was most common in promotional events. Such event participation predicted engagement with regularly recurring programming and school- and district-level establishment of biking- and walking-facilitative policies. Lower income schools were more likely to establish recurring bike and walk programs than wealthier schools, whereas rural schools were less likely than city schools to participate in promotional events, yet equally as likely as other schools to participate in recurring bike and walk programs.

Conclusions

Schools’ engagement with the North Carolina ARTS Project diffused despite many schools’ rural geographies and lower socioeconomic status. Further, participation in one-time promotional events can portend schools’ establishment of recurring walking and biking programs and supportive policies.