bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol of a phase II clinical trial of oral metformin for the intravesical treatment of non-muscle invasive bladder cancer
Authors: Molenaar Remco J. , van Hattum Jons W. , Brummelhuis Iris S. , Oddens Jorg R. , Savci-Heijink C. Dilara , Boevé Egbert R. , van der Meer Saskia A. , Witjes J. Fred , Pollak Michael N. , de Reijke Theo M. , Wilmink Johanna W. 
Published: November 2019

Abstract
Background
Non-muscle-invasive bladder cancer (NMIBC) is the most common neoplasm of the urinary tract and requires life-long invasive surveillance to detect disease recurrence. Currently, there are no effective oral therapies that delay disease recurrence or progression. We recently demonstrated that in mice, metformin accumulates unchanged in the urine. Urothelial cells are exposed to metformin concentrations ~ 240-fold higher than in serum. This was effective in the treatment of mouse bladder cancer models.

Methods
We describe the protocol of a multi-centre, open-label, phase II clinical trial of metformin in up to 49 evaluable patients with intermediate-risk NMIBC with the aim to determine the overall response to administration of oral metformin for 3 months on a marker tumour deliberately left following transurethral resection of multiple, papillary NMIBC tumours. All patients will receive metformin orally at doses up to 3000 mg per day. Metformin treatment will start within 2 weeks following transurethral resection of all tumours except one marker lesion. After 3 months of metformin treatment, the effect of metformin on the marker lesion is evaluated by cystoscopy and biopsy under anaesthesia. Residual tumour, if present at this evaluation, will be resected. In case of complete disappearance of the marker lesion, the former tumour area will be biopsied. The primary outcome is the complete response rate of the marker lesion, as determined by decentralised scoring of pre- and post-treatment cystoscopy images by expert independent urologists. Secondary outcomes are the partial response rate, overall safety of metformin and the duration of the time to recurrence.

Discussion
Preclinical studies show the potential role of oral metformin treatment in the management of NMIBC. It could offer an alternative to current adjuvant intravesical treatment. If positive, the reported results of this study could warrant further phase III trials to compare the efficacy of metformin against current treatments of intravesical installations with chemotherapy or Bacillus Calmette-Guérin (BCG).

Trial registration
This trial is registered in ClinicalTrials.gov under NCT03379909.
Nrf2 gene mutation and single nucleotide polymorphism rs6721961 of the Nrf2 promoter region in renal cell cancer
Authors: Yamaguchi Yoshiyuki , Kamai Takao , Higashi Satoru , Murakami Satoshi , Arai Kyoko , Shirataki Hiromichi , Yoshida Ken-Ichiro 
Published: November 2019

AbstractBackgroundNuclear factor erythroid 2–related factor 2 (Nrf2) is involved in cell proliferation by promotion of metabolic activity. It is also the major regulator of antioxidants and has a pivotal role in tumor cell proliferation and resistance to chemotherapy. Accordingly, we investigated the role of Nrf2 in renal cell carcinoma (RCC).MethodsIn 50 patients who had metastatic RCC and received cytoreductive nephrectomy, we performed Nrf2 gene mutation analysis using targeted next-generation sequencing, as well as investigating a specific single nucleotide polymorphism (SNP; rs6721961) in the Nrf2 promoter region and Nrf2 protein expression.ResultsTargeted next-generation sequencing revealed that five tumors had SNPs of Nrf2 associated with amino acid sequence variation, while 11 tumors had SNPs of Kelch-like ECH-associated protein 1 gene, 35 had SNPs of von Hippel-Lindau gene, and none had SNPs of fumarate hydratase gene. The three genotypes of rs6721961 showed the following frequencies: 60% for C/C, 34% for C/A, and 6% for A/A. Nrf2 mutation and the C/A or A/A genotypes were significantly associated with increased Nrf2 protein expression (p = 0.0184 andp = 0.0005, respectively). When the primary tumor showed Nrf2 gene mutation, the C/A or A/A genotype, or elevated Nrf2 protein expression, the response of metastases to vascular endothelial growth factor-targeting therapy was significantly worse (p = 0.0142,p = 0.0018, andp <  0.0001, respectively), and overall survival was significantly reduced (p = 0.0343,p = 0.0421, andp <  0.0001, respectively). Elevated Nrf2 protein expression was also associated with shorter survival according to multivariate Cox proportional analysis.ConclusionThese findings suggest an associated between progression of RCC and Nrf2 signaling.
Case report: palmar herpetic whitlow and forearm lymphangitis in a 10-year-old female
Authors: Lieberman Leora , Castro Daniel , Bhatt Avni , Guyer Fred 
Published: November 2019

Abstract
Background
Herpetic whitlow is a viral infection caused by the herpes simplex virus (HSV) types 1 or 2, and occurs in the pediatric population primarily on the fingers and toes due to autoinoculation from oral secretions. Because of this cited prevalence, other locations of herpetic whitlow may go unrecognized.

Case presentation
We present an atypical presentation of palmar herpetic whitlow with delayed recognition and associated viral lymphangitis. The patient presented as a transfer from an outside hospital with a progressive, three-day history of a suspected left hand abscess preceded by left hand pain and itching. She was initially evaluated by Orthopedic Surgery, who described an erythematous, edematous, tender, left palmar abscess with associated erythematous streaking up her forearm. The lesion was surgically managed with an incision and drainage. Wound cultures were obtained during which “minimal drainage” was noted. After admission to the General Pediatrics Hospital service, the lesion was noted to appear vesicular and subsequently obtained PCR samples were positive for HSV type 1, confirming her diagnosis of herpetic whitlow. Although she remained afebrile with negative wound cultures throughout her hospitalization, a secondary bacterial infection could not be conclusively excluded due to the accompanying lymphangitis. Thus, she was discharged with oral antibiotics and anticipatory guidance of potential recurrence of palmar lesions.

Conclusions
Herpetic whitlow should be included in the differential diagnosis of palmar lesions that appear vesicular or abscess-like to ensure appropriate treatment. Additionally, these palmar lesions may present with associated lymphangitis without evidence of bacterial infection.
Long working hours are associated with unmet dental needs in south Korean male adults who have experienced dental pain
Authors: Kim Yitak , Lee Sangwon , Kim Juyeong , Park Eun-Cheol , Jang Sung-In 
Published: November 2019

Abstract
Backgrounds
We explored the association between working hours and unmet dental needs among adults who have experienced dental pain, and how this relationship varied by demographic and lifestyle factors.

Methods
We used the data of 9594 adults who reported dental pain from the Korea National Health and Nutrition Examination Survey (KNHANES) V and VI. We conducted a logistic regression analysis to determine the association between working hours and unmet dental needs, followed by a subgroup analysis and Cochran-Armitage trend tests.

Results
Among the 4203 male subjects, 1661 (39.5%) experienced unmet dental needs. They also showed a significant dose-response relationship between working hours and unmet dental needs (OR 1.21 [95% CI 0.97–1.51], OR 1.30 [95% CI 0.99–1.69], OR 1.33 [95% CI 1.04–1.71], OR 1.58 [95% CI 1.21–2.07] compared to no working hours), whereas female participants did not. The significance of the association was preserved among participants with increased consumption of alcohol, urban residence, and who brushed their teeth at least twice a day. It was also stronger among those who lacked access to dental services or did not perceive the need for dental care.

Conclusion
Among adults who have experienced dental pain, unmet dental needs had higher odds of occurring in males who worked longer, and this relationship appears to be influenced by consumption of alcohol, region of residence, tooth-brushing frequency, and access to and perception of dental care. Accordingly, policies should be drafted to reduce unmet needs by considering these factors.
Effectiveness of smart phone application use as continuing medical education method in pediatric oral health care: a randomized trial
Authors: Bonabi M. , Mohebbi S. Z. , Martinez-Mier E. A. , Thyvalikakath T. P. , Khami M. R. 
Published: November 2019

Abstract
Background
Continuing education aims at assisting physicians to maintain competency and expose them to emerging issues in their field. Over the last decade, approaches to the delivery of educational content have changed dramatically as medical education at all levels is now benefitting from the use of web-based content and applications for mobile devices. The aim of the present study is to investigate through a randomized trial the effectiveness of a smart phone application to increase public health service physicians’ (PHS physicians) knowledge regarding pediatric oral health care.

Method
Five of all seven DHCs (District Health Center) in Tehran, which were under the supervision of Tehran University of Medical Sciences and Iran University of Medical Sciences, were selected for our study. Physicians of one DHC had participated in a pilot study. All PHS physicians in the other four centers were invited to the current study on a voluntary basis (n = 107). They completed a self-administered questionnaire regarding their knowledge, attitudes, practice in pediatric dentistry, and background. PHS physicians were assigned randomly to intervention and control groups; those in the intervention group, received a newly designed evidence-based smartphone application, and those in the control group received a booklet, a CME seminar, and a pamphlet. A post-intervention survey was administered 4 months later and t-test and repeated measures ANCOVA (Analysis of Covariance) were performed to measure the difference in the PHS physicians’ knowledge, attitude and practice.

Results
In both groups, the mean knowledge scores were significantly higher (p-Value < 0.001) in post-intervention data compared to those at baseline. Similar results existed in attitude and practice scores. Although the scores in knowledge in the intervention group indicating potentially greater improvement when compared to those of the control group, the differences between the two groups were not statistically significant (dif: 0.84, 95% CI − 0.35 to 2.02).

Conclusion
In the light of the limitations of the present study, smart phone applications could improve knowledge, attitude and practice in physicians although this method was not superior to the conventional method of CME.

Trial registration
Our clinical trial had been registered in Iranian Registry of Clinical Trials (registration code: IRCT2016091029765N1).
The relationship between study skills and depressive symptoms among medical residents
Authors: AlFaris Eiad , AlMughthim Muhannad , Irfan Farhana , Al Maflehi Nassr , Ponnamperuma Gominda , AlFaris Huda E. , Ahmed Abdullah M. A. , van der Vleuten Cees 
Published: November 2019

Abstract
Background
The cost of depression among residents is staggering as it extends into the quality and safety of patient care. Finding an explanation to resident depression by investigating the associated factors is therefore important. Study skills can be a possible factor, and a clear gap in the literature exists in this regard. We sought to investigate the relationship between depressive symptoms among residents and their study skills.

Methods
This was a correlational study and a non-probability sample of 240 residents completed the Beck Depression Inventory II (BDI-II) and the Study Skills Inventory (SSI). Chi-square test was used to compare different categorical variables, while student t-test and ANOVA for continuous data. Pearson’s correlation coefficient was performed to find the relationship between depressive symptoms and study skills and the association that these measures have with the demographic variables.

Results
Overall, 186 residents (76%) filled out the questionnaire. The SSI total score was found to have a significant negative association with the BDI-II depression score (Pearson correlation = − 0.447and p < 0.000). No significant association was found between the total SSI score and the residents’ sex, age, marital status, smoking status, training years or specialties.

Conclusion
Poor study skills were found to be correlated with higher depressive symptoms. Future studies are required to develop a deeper understanding of this relationship and reconfigure the approach to study skills for the well-being of the future physicians.
“Assessment of the social influence and facilitating conditions that support nurses’ adoption of hospital electronic information management systems (HEIMS) in Ghana using the unified theory of acceptance and use of technology (UTAUT) model”
Authors: Zhou Lu Lin , Owusu-Marfo Joseph , Asante Antwi Henry , Antwi Maxwell Opuni , Kachie Arielle Doris Tetgoum , Ampon-Wireko Sabina 
Published: November 2019

Abstract
Background
Hospital electronic information management systems (HEIMS) are widely used in Ghana, and hence its performance must be carefully assessed. Nurses as clinical health personnel are the largest cluster of hospital staff and are the pillar of healthcare delivery. Therefore, they play a crucial role in the adoption and assessment of HEIMSs in Ghana. This report sought to assess the “Social Influence” (SI) and “Facilitating Conditions” (FC) that support Nurses’ Acceptance of HEIMS in Ghana using the “Unified Theory of Acceptance and Use of Technology” (UTAUT) model.

Methods
This study applied a non-experimental survey design. An electronic platform questionnaire on smartphones was used to collect data on 660 nurses. Statistically, AMOS Structural Equation Modelling (SEM) version 22.0 was employed to examine the research model.

Results
“Behavioral Intention” (BI) to HEIMS use was significantly predicted by SI and FC (p < 0.001). Notably, both SI and FC had an influence on nurses’ use behavior (UB) with behavioral intention (BI) as the mediator, which explains a total of 42.1% variance in the intention of nurses to use HEIMS. Likewise, UB of HEIMS was also significantly predicted by SI (R2 = 43.2) and BI (R2 = 0.39.6) with both constructs explaining a total of 51.7% of the variance in nurses’ acceptance to use HEIMS.

Conclusion
Nurses’ adoption of HEIMS in terms of the UB was influenced by SI and BI, whiles SI and FC had the strongest influence on BI (serving as mediator) of UB to adopt and use HEIMS among the nurses in Ghanaian hospitals.
Ethical challenges of seclusion in psychiatric inpatient wards: a qualitative study of the experiences of Norwegian mental health professionals
Authors: W. Haugom Espen , Ruud Torleif , Hynnekleiv Torfinn 
Published: November 2019

AbstractBackgroundSeclusion is an invasive clinical intervention used in inpatient psychiatric wards as a continuation of milieu therapy with vast behavioural implications that raise many ethical challenges. Seclusion is in Norway defined as an intervention used to contain the patient, accompanied by staff, in a single room, a separate unit, or an area inside the ward. Isolation is defined as the short-term confinement of a patient behind a locked or closed door with no staff present. Few studies examine how staff experiences the ethical challenges they encounter during seclusion. By making these challenges explicit and reflecting upon them, we may be able to provide better care to patients. The aim of this study is to examine how clinical staff in psychiatric inpatient wards describes and assess the ethical challenges of seclusion.MethodsThis study was based on 149 detailed written descriptions of episodes of seclusion from 57 psychiatric wards. A descriptive and exploratory approach was used. Data were analysed using qualitative content analysis.ResultsThe main finding is that the relationship between treatment and control during seclusion presents several ethical challenges. This is reflected in the balance between the staff’s sincere desire to provide good treatment and the patients’ behaviour that makes control necessary. Particularly, the findings show how taking control of the patient can be ethically challenging and burdensome and that working under such conditions may result in psychosocial strain on the staff. The findings are discussed according to four core ethical principles: autonomy, beneficence, non-maleficence, and justice.ConclusionEthical challenges seem to be at the core of the seclusion practice. Systematic ethical reflections are one way to process the ethical challenges that staff encounters. More knowledge is needed concerning the ethical dimensions of seclusion and alternatives to seclusion, including what ethical consequences the psychosocial stress of working with seclusion have for staff.
Validation of the AJCC prognostic stage for HER2-positive breast cancer in the ShortHER trial
Authors: Dieci Maria Vittoria , Bisagni Giancarlo , Brandes Alba A. , Frassoldati Antonio , Cavanna Luigi , Giotta Francesco , Aieta Michele , Gebbia Vittorio , Musolino Antonino , Garrone Ornella , Donadio Michela , Rimanti Anita , Beano Alessandra , Zamagni Claudio , Soto Parra Hector , Piacentini Federico , Danese Saverio , Ferro Antonella , Cagossi Katia , Sarti Samanta , Gambaro Anna Rita , Romito Sante , Bazan Viviana , Amaducci Laura , Moretti Gabriella , Foschini Maria Pia , Balduzzi Sara , Vicini Roberto , D’Amico Roberto , Griguolo Gaia , Guarneri Valentina , Conte Pier Franco 
Published: November 2019

Abstract
Background
The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial.

Methods
The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Patients were classified according to the anatomic and the prognostic stage. Distant disease-free survival (DDFS) was calculated from randomization to distant relapse or death.

Results
A total of 1244 patients were included. Compared to anatomic stage, the prognostic stage downstaged 41.6% (n = 517) of patients to a more favorable stage category.
Five-year DDFS based on anatomic stage was as follows: IA 96.6%, IB 94.1%, IIA 92.4%, IIB 87.3%, IIIA 81.3%, IIIC 70.5% (P < 0.001). Five-year DDFS according to prognostic stage was as follows: IA 95.7%, IB 91.4%, IIA 86.9%, IIB 85.0%, IIIA 77.6%, IIIC 67.7% (P < 0.001). The C index was similar (0.69209 and 0.69249, P = 0.975).
Within anatomic stage I, the outcome was similar for patients treated with 9 weeks or 1 year trastuzumab (5-year DDFS 96.2% and 96.6%, P = 0.856). Within prognostic stage I, the outcome was numerically worse for patients treated with 9 weeks trastuzumab (5-year DDFS 93.7% and 96.3%, P = 0.080).

Conclusions
The prognostic stage downstaged 41.6% of patients, while maintaining a similar prognostic performance as the anatomic stage. The prognostic stage is valuable in counseling patients and may serve as reference for a clinical trial design. Our data do not support prognostic stage as guidance to de-escalate treatment.

Trial registration
EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.
Molecular characterization and distribution of Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi from yaks in Tibet, China
Authors: Wu Yayun , Chang Yankai , Zhang Xiangqian , Chen Yuancai , Li Dongfang , Wang Lu , Zheng Shuangjian , Wang Rongjun , Zhang Sumei , Jian Fuchun , Ning Changshen , Li Jiakui , Zhang Longxian 
Published: November 2019

Abstract
Background
With worldwide distribution and importance for veterinary medicine, Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi have been found in a wide variety of vertebrate hosts. At present, few available molecular data can be used to understand the features of genetic diversity of these pathogens in areas without or less intensive farming. Dominated by grazing, Tibet is a separate geographic unit in China and yaks are in frequent contact with local herdsmen and necessary for their daily life. Therefore, to investigate the distribution of these pathogens in yaks of Tibet, 577 fecal specimens were screened using nested PCR for the presence and genotypes of the three intestinal pathogens.

Results
The overall prevalence of Cryptosporidium spp., G. duodenalis, and E. bieneusi were 1.4% (8/577), 1.7% (10/577), and 5.0% (29/577), respectively. Cryptosporidium andersoni (n = 7) and Cryptosporidium bovis (n = 1) were detected by sequence analysis of the SSU rRNA gene. Genotyping at the SSU rRNA and triosephosphate isomerase genes suggested that all G. duodenalis positive specimens belonged to assemblage E. Sequence analysis of the internal transcribed spacer gene identified six known E. bieneusi genotypes: BEB4 (n = 11), I (n = 6), D (n = 5), J (n = 2), CHC8 (n = 1), and BEB6 (n = 1). One subtype (A5,A4,A2,A1) for C. andersoni and three multilocus genotypes for E. bieneusi were identified by multilocus sequence typing.

Conclusions
We report for the first time the status of three enteric pathogens infection simultaneously for grazing yaks in Tibet. Yaks in our study are likely to impose a low zoonotic risk for humans. The molecular epidemiology data add to our knowledge of the characteristics of distribution and transmission for these pathogens in Tibet and their zoonotic potential and public health significance.
Diverging effects of premature birth and bronchopulmonary dysplasia on exercise capacity and physical activity – a case control study
Authors: Ruf Katharina , Thomas Wolfgang , Brunner Maximilian , Speer Christian P. , Hebestreit Helge 
Published: November 2019

AbstractBackgroundExtreme prematurity has been associated with exercise intolerance and reduced physical activity. We hypothesized that children with bronchopulmonary dysplasia (BPD) would be especially affected based on long-term lung function impairments. Therefore, the objective of this study was to compare exercise capacity and habitual physical activity between children born very and extremely preterm with and without BPD and term-born children.MethodsTwenty-two school-aged children (aged 8 to 12 years) born with a gestational age < 32 weeks and a birthweight < 1500 g (9 with moderate or severe BPD (=BPD), 13 without BPD (=No-BPD)) and 15 healthy term-born children (=CONTROL) were included in the study. Physical activity was measured by accelerometry, lung function by spirometry and exercise capacity by an incremental cardiopulmonary exercise test.ResultsPeak oxygen uptake was reduced in the BPD-group (83 ± 11%predicted) compared to the No-BPD group (91 ± 8%predicted) and the CONTROL group (94 ± 9%predicted). In a general linear model, variance of peak oxygen uptake was significantly explained by BPD status and height but not by prematurity (p < 0.001).Compared to CONTROL, all children born preterm spent significantly more time in sedentary behaviour (BPD 478 ± 50 min, No-BPD 450 ± 52 min, CONTROL 398 ± 56 min,p < 0.05) and less time in moderate-to-vigorous-physical activity (BPD 13 ± 8 min, No-BPD 16 ± 8 min, CONTROL 33 ± 16 min,p < 0.001). Prematurity but not BPD contributed significantly to explained variance in a general linear model of sedentary behaviour and likewise moderate-to-vigorous-physical activity (p < 0.05 andp < 0.001 respectively).ConclusionIn our cohort, BPD but not prematurity was associated with a reduced exercise capacity at school-age. However, prematurity regardless of BPD was related to less engagement in physical activity and more time spent in sedentary behaviour. Thus, our findings suggest diverging effects of prematurity and BPD on exercise capacity and physical activity.