bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extended versus non-extended lymphadenectomy during radical cystectomy for patients with bladder cancer: a meta-analysis of the effect on long-term and short-term outcomes
Authors: Wang Yu-Chen , Wu Jie , Dai Bo , Shen Yi-Jun , Ma Chun-Guang , Ye Ding-Wei , Zhu Yi-Ping 
Published: December 2019

Abstract
Background
Pelvic lymphadenectomy (PLND) is an integral part of curative surgery for high-risk non-muscle invasive and muscle-invasive bladder cancer. The therapeutic value of extended PLND is controversial.

Methods
We conducted a comprehensive online search in PubMed, EMBASE, and the Cochrane Library databases for relevant literature directly comparing extended PLND (e-PLND) with non-extended PLND (ne-PLND) from database inception to June 2019. We performed the meta-analysis to evaluate the impact of PLND templates on recurrence-free survival (RFS), disease-specific survival (DSS), overall survival (OS), rates of postoperative major complications, and mortality within 90 days of surgery.

Results
A total of 10 studies involving 3979 patients undergoing either e-PLND or ne-PLND were included. The results showed that e-PLND was significantly associated with better RFS (HR 0.74, 95% CI 0.62–0.90, p = 0.002) and DSS (HR 0.66, 95% CI 0.55–0.79, p < 0.001). However, no correlation was found between e-PLND template and a better OS (HR 0.93, 95% CI 0.55–1.58, p = 0.79). Postoperative major complications were similar between e-PLND group and ne-PLND group, as was mortality within 90 days of surgery.

Conclusion
e-PLND template is correlated with favorable RFS and DSS outcomes for patients with bladder cancer. e-PLND did not have more postoperative major complications than did ne-PLND.
How and why do win–win strategies work in engaging policy-makers to implement Health in All Policies? A multiple-case study of six state- and national-level governments
Authors: Kokkinen Lauri , Freiler Alix , Muntaner Carles , Shankardass Ketan 
Published: December 2019

Abstract
Background
Much of the research about Health in All Policies (HiAP) implementation is descriptive, and there have been calls for more evaluative evidence to explain how and why successes and failures have occurred. In this cross-case study of six state- and national-level governments (California, Ecuador, Finland, Norway, Scotland and Thailand), we tested hypotheses about win–win strategies for engaging policy-makers in HiAP implementation drawing on components identified in our previous systems framework.

Methods
We used two sources of data — key informant interviews and peer-reviewed and grey literature. Using a protocol, we created context–mechanism–outcome pattern configurations to articulate mechanisms that explain how win–win strategies work and fail in different contexts. We then applied our evidence for all cases to the systems framework. We assessed the quality of evidence within and across cases in terms of triangulation of sources and strength of evidence. We also strengthened hypothesis testing using replication logic.

Results
We found robust evidence for two mechanisms about how and why win–win strategies build partnerships for HiAP implementation — the use of shared language and the value of multiple outcomes. Within our cases, the triangulation was strong, both hypotheses were supported by literal and contrast replications, and there was no support against them. For the third mechanism studied, using the public-health arguments win–win strategy, we only found evidence from Finland. Based on our systems framework, we expected that the most important system components to using win–win strategies are sectoral objectives, and we found empirical support for this prediction.

Conclusions
We conclude that two mechanisms about how and why win–win strategies build partnerships for HiAP implementation — the use of shared language and the value of multiple outcomes — were found as relevant to the six settings. Both of these mechanisms trigger a process of developing synergies and releasing potentialities among different government sectors and these interactions between sectors often work through sectoral objectives. These mechanisms should be considered when designing future HiAP initiatives and their implementation to enhance the emergence of non-health sector policy-makers’ engagement.
Is fibrodysplasia ossificans progressiva an interleukin-1 driven auto-inflammatory syndrome?
Authors: Haviv Ruby , Moshe Veronica , De Benedetti Fabrizio , Prencipe Giusi , Rabinowicz Noa , Uziel Yosef 
Published: December 2019

Abstract
Background
Fibrodysplasia ossificans progressiva (FOP) is the most catastrophic form of heterotopic ossification, due to ongoing intracellular signaling through the bone morphogenic protein pathway. The paroxysmal appearance of inflammatory lumps and elevated inflammatory markers during flares, suggest that FOP is an auto-inflammatory disease. Based on evidence, demonstrating a role for interleukin-1β (IL-1β) in other forms of heterotopic ossification, we hypothesized that treating FOP patients with anti-IL-1 agents could help lower the rate of FOP paroxysms and/or limit the symptoms and residual lesions.

Case presentation
A 13.5-year-old Arab boy was diagnosed with FOP. Treatment with anti-inflammatory drugs did not change the disease course. New lumps appeared in a rate of approximately one every 8 days. Treatment with the anti-IL-1 agents anakinra and canakinumab resulted in significantly lower rate of paroxysms (every 22–25 days, of which almost all involved only 2 existing lumps), as well as shorter duration. High levels of IL-1β were found in the patient’s plasma samples, collected during a paroxysm that appeared 8 weeks after the last canakinumab dose. In contrast, IL-1β plasma levels were undetectable in the previous three plasma samples, obtained while he was treated with anti-IL-1 agents.

Conclusions
Our data demonstrate the efficacy of anti-IL-1 agents in the treatment of a patient with FOP. Results showing the marked increase in IL-1β plasma levels during a paroxysm support a role for IL-1β in the pathogenesis of FOP and further provide the rationale for the use of anti-IL-1 agents in FOP treatment.
“I feel myself incomplete, and I am inferior to people”: experiences of Sudanese women living with obstetric fistula in Khartoum, Sudan
Authors: Ahmed Salma A. E. , Thorsen Viva C. 
Published: December 2019

Abstract
Background
Obstetric fistula is among the most devastating maternal morbidities that occur as a result of prolonged, obstructed labor. Usually, the child dies in a large number of the cases. Moreover, some of the women become infertile while the majority suffer physical, psychosocial and economic challenges. Approximately 5000 new cases of obstetric fistula occur in Sudan each year. However, their experiences are under documented. Therefore, this study aimed to shed light on their daily lives living with obstetric fistula and how they cope.

Methods
Using a qualitative study design, 19 women living with obstetric fistula were interviewed. The study took place in the fistula ward located in Khartoum hospital and the fistula re-integration center in Khartoum, Sudan. Thematic analysis approach was employed. Stigma and coping theories guided the data collection, analysis, and discussion of the findings.

Findings
Women in our study suffered a challenging physical life due to leakage of urine. In addition, they encountered all forms of stigmatization. Women used both emotion-focused and problem-focused coping techniques to mitigate the consequences of obstetric fistula.

Conclusion
The study findings underscore the importance of obstetric fistula prevention programs and the urgency of repair surgeries to alleviate women’s suffering. Community sensitization, rehabilitation and re-integration of women back to their communities are also important strategies on their journey to wholeness.
NAD-linked mechanisms of gene de-repression and a novel role for CtBP in persistent adenovirus infection of lymphocytes
Authors: Dickherber Megan L. , Garnett-Benson Charlie 
Published: December 2019

AbstractBackgroundAdenovirus (AdV) infection is ubiquitous in the human population and causes acute infection in the respiratory and gastrointestinal tracts. In addition to lytic infections in epithelial cells, AdV can persist in a latent form in mucosal lymphocytes, and nearly 80% of children contain viral DNA in the lymphocytes of their tonsils and adenoids. Reactivation of latent AdV is thought to be the source of deadly viremia in pediatric transplant patients. Adenovirus latency and reactivation in lymphocytes is not well studied, though immune cell activation has been reported to promote productive infection from latency. Lymphocyte activation induces global changes in cellular gene expression along with robust changes in metabolic state. The ratio of free cytosolic NAD+/NADH can impact gene expression via modulation of transcriptional repressor complexes. The NAD-dependent transcriptional co-repressor C-terminal Binding Protein (CtBP) was discovered 25 years ago due to its high affinity binding to AdV E1A proteins, however, the role of this interaction in the viral life cycle remains unclear.MethodsThe dynamics of persistently- and lytically-infected cells are evaluated. RT-qPCR is used to evaluate AdV gene expression following lymphocyte activation, treatment with nicotinamide, or disruption of CtBP-E1A binding.ResultsPMA and ionomycin stimulation shifts the NAD+/NADH ratio in lymphocytic cell lines and upregulates viral gene expression. Direct modulation of NAD+/NADH by nicotinamide treatment also upregulates early and late viral transcripts in persistently-infected cells. We found differential expression of the NAD-dependent CtBP protein homologs between lymphocytes and epithelial cells, and inhibition of CtBP complexes upregulates AdV E1A expression in T lymphocyte cell lines but not in lytically-infected epithelial cells.ConclusionsOur data provide novel insight into factors that can regulate AdV infections in activated human lymphocytes and reveal that modulation of cellular NAD+/NADH can de-repress adenovirus gene expression in persistently-infected lymphocytes. In contrast, disrupting the NAD-dependent CtBP repressor complex interaction with PxDLS-containing binding partners paradoxically alters AdV gene expression. Our findings also indicate that CtBP activities on viral gene expression may be distinct from those occurring upon metabolic alterations in cellular NAD+/NADH ratios or those occurring after lymphocyte activation.
Peer involvement and cross-sector efforts in establishing integrated treatment of hepatitis C virus infection for people with substance use disorders: experiences from Norway
Authors:   for the INTRO-HCV Study Group, Lygren Ole Jørgen , Bjørnestad Ronny , Løberg Else-Marie , Bonnier Martine Lepsøy , Buljovcic Vibeke Bråthen , Johansson Kjell Arne , Fadnes Lars T. 
Published: December 2019

Abstract
Background
For people with opioid dependence in Norway, chronic hepatitis C virus (HCV) infections contribute to high mortality and high morbidity. Around 50% of patients in medically assisted rehabilitation (MAR) have been shown to have HCV, and the current prevention and control efforts have been mostly unsuccessful. Thus, there is a need for new strategies for people-centred service delivery and innovative methods to improve health outcomes.

Methods
Over the last few years, the city of Bergen, Norway, has developed a cross-sector collaboration with substantial peer involvement in research and health provision related to substance use. User group representatives for people receiving MAR, addiction medicine health personnel, infectious disease specialists, policy makers in the municipality, low-threshold health care centres for people with substance use disorders in Bergen Municipality and researchers in the INTRO-HCV project have made concerted efforts in this regard. We will present here some of the strategies and steps we have taken.

Results
We have established an integrated HCV treatment scheme for people who inject drugs or who have opioid dependence. More than 800 persons have been tested for HCV within these frames, and more than 250 persons have been given treatment for HCV within the project. The integrated treatment of HCV is offered both in MAR outpatient clinics, municipal low-threshold healthcare centres, and local and regional prisons. The preliminary results indicate an increase in HCV treatment uptake among those receiving integrated treatment (96% initiating treatment compared to 75%). The user group organisation ProLAR Nett has established an outreach service to screen for HCV, increase awareness and reduce the proportion of people unknowingly living with HCV while informing and motivating people to receive treatment. Together with the other stake holders, peer user group, health care, research planning, concert events, and policy panels have been held.

Conclusions
Peer involvement seems to have increased testing rates for HCV and acknowledgment of its importance. This seems to have improved health care for people with opioid dependence in Bergen over the last few years, particularly relating to the treatment of HCV. These experiences might be helpful in the planning of integrated policies in other settings that seek to eliminate the HCV endemic.
Risk factors for refracture after plate removal for midshaft clavicle fracture after bone union
Authors: Tsai Shang-Wen , Ma Hsuan-Hsiao , Hsu Fang-Wei , Chou Te-Feng Arthur , Chen Kun-Hui , Chiang Chao-Ching , Chen Wei-Ming 
Published: December 2019

Abstract
Background
Open reduction and internal fixation (ORIF) with plates and screws is one of the treatment options for clavicle fractures. However, an additional operation for implant removal after union of the fracture is commonly performed due to a high incidence of hardware irritation. Despite union of the fracture, a subsequent refracture might occur after removal of the implant which requires additional surgeries for fixation. This study aims to determine the risk factors associated with refracture of the clavicle after hardware removal.

Methods
We retrospectively reviewed the medical records of 278 patients that were diagnosed with a midshaft clavicle fracture (male 190; female 88) that had (1) undergone ORIF of the clavicle with plates and (2) received a second operation for removal of hardware after solid union of the fracture between 2010 and 2017. Their mean age was 40.1 ± 15.1 years, and mean interval from fixation to plate removal was 12.5 ± 7.5 months. The patients were then divided into two groups based on the presence of refracture (n = 20) or without refracture (n = 258). We analyzed patient demographics, interval between fixation and implant removal, fracture classification (AO/OTA, Robinson), fixation device, whether wires or interfragmentary screws were used, clavicular length, and bone diameter at the fracture site.

Results
The overall refracture rate was 7.2%, and the mean interval between plate removal and refracture was 23.9 days. A multivariate analysis showed that female (adjusted odds ratio [aOR] 4.74; 95% CI 1.6–14.1) and body mass index [BMI] (for every 1-unit decrease, aOR 1.25; 95% CI 1.06–1.48) were risk factors for refracture. In women, BMI was the only risk factor. The optimal BMI cutoff value was 22.73. In a female patient with a lower BMI, the refracture rate was 29.8%.

Conclusions
There are no significant radiographic parameters associated with refracture. Routine plate removal in a female patient with a low BMI after bony union of a midshaft clavicle fracture is not recommended because of a high refracture rate.
LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same
Authors: Berwick Daniel C. , Heaton George R. , Azeggagh Sonia , Harvey Kirsten 
Published: December 2019

AbstractSince the discovery of leucine-rich repeat kinase 2 (LRRK2) as a protein that is likely central to the aetiology of Parkinson’s disease, a considerable amount of work has gone into uncovering its basic cellular function. This effort has led to the implication of LRRK2 in a bewildering range of cell biological processes and pathways, and probable roles in a number of seemingly unrelated medical conditions. In this review we summarise current knowledge of the basic biochemistry and cellular function of LRRK2. Topics covered include the identification of phosphorylation substrates of LRRK2 kinase activity, in particular Rab proteins, and advances in understanding the activation of LRRK2 kinase activity via dimerisation and association with membranes, especially via interaction with Rab29. We also discuss biochemical studies that shed light on the complex LRRK2 GTPase activity, evidence of roles for LRRK2 in a range of cell signalling pathways that are likely cell type specific, and studies linking LRRK2 to the cell biology of organelles. The latter includes the involvement of LRRK2 in autophagy, endocytosis, and processes at thetrans-Golgi network, the endoplasmic reticulum and also key microtubule-based cellular structures. We further propose a mechanism linking LRRK2 dimerisation, GTPase function and membrane recruitment with LRRK2 kinase activation by Rab29. Together these data paint a picture of a research field that in many ways is moving forward with great momentum, but in other ways has not changed fundamentally. Many key advances have been made, but very often they seem to lead back to the same places.
Global burden of breast cancer and attributable risk factors in 195 countries and territories, from 1990 to 2017: results from the Global Burden of Disease Study 2017
Authors: Li Na , Deng Yujiao , Zhou Linghui , Tian Tian , Yang Si , Wu Ying , Zheng Yi , Zhai Zhen , Hao Qian , Song Dingli , Zhang Dai , Kang Huafeng , Dai Zhijun 
Published: December 2019

AbstractBackgroundStatistical data on the incidence, mortality, and burden of breast cancer and the relevant risk factors are valuable for policy-making. We aimed to estimate breast cancer incidence, deaths, and disability-adjusted life years (DALYs) by country, gender, age group, and social-demographic status between 1990 and 2017.MethodsWe extracted breast cancer data from the 2017 Global Burden of Disease (GBD) study from 1990 through 2017 in 195 countries and territories. Data about the number of breast cancer incident cases, deaths, DALYs, and the age-standardized rates were collected. We also estimated the risk factors attributable to breast cancer deaths and DALYs using the comparative risk assessment framework of the GBD study.ResultsIn 2017, the global incidence of breast cancer increased to 1,960,681 cases. The high social-development index (SDI) quintile included the highest number of breast cancer death cases. Between 2007 and 2017, the ASDR of breast cancer declined globally, especially in high SDI and high middle SDI countries. The related DALYs were 17,708,600 in 2017 with high middle SDI quintile as the highest contributor. Of the deaths and DALYs, alcohol use was the greatest contributor in most GBD regions and other contributors included high body mass index (BMI) and high fasting plasma glucose.ConclusionThe increasing global breast cancer burden is mainly observed in lower SDI countries; in higher SDI countries, the breast cancer burden tends to be relieving. Therefore, steps against attributable risk factors should be taken to reduce breast cancer burden in lower SDI countries.
Early onset retinal dystrophies: clinical clues to diagnosis for pediatricians
Authors: Suppiej Agnese , Marino Silvia , Reffo Maria Eleonora , Maritan Veronica , Vitaliti Giovanna , Mailo Janette , Falsaperla Raffaele 
Published: December 2019

Abstract
Introduction
Inherited retinal dystrophies are major cause of severe progressive vision loss in children. Early recognition and diagnosis are essential for timely visual rehabilitation during the appropriate stages of the visual development, as well as for genetic diagnosis and possible gene therapy. The aim of this study is to characterize a pattern of the initial visual symptoms, which could help the pediatricians and the primary care providers to suspect an inherited retinal disorder in its early stage.

Methods
We analyzed the initial clinical symptoms, based on parental report during the first visit to specialist, in 50 children diagnosed with retinal dystrophy confirmed by full-field electroretinography. The analysis included the age of symptoms onset and the type of visual symptoms, both in the total population and in the following diagnostic subgroups: rod-cone dystrophy (n.17), cone-rod dystrophy (n.12), achromatopsia (n.13), congenital stationary night blindness (n.6) and Leber’s congenital amaurosis (n.2).

Results
The majority of children (80%) had the onset of clinical symptoms before one year of age. The most frequent visual complaints reported by parents were nystagmus (76%), visual loss (28%) and photophobia (8%). Nystagmus was the first symptom reported by parents if the disease onset was before the age of six months, while the onset after the six months of age was more likely associated with the complain of vision loss.

Conclusions
Low vision and nystagmus observed by parents, particularly in the first year of life, may represent a red flag, prompting an appropriate ophthalmological workup for inherited retinal dystrophy.
Parasitological, serological and molecular survey of camel trypanosomiasis in Somalia
Authors: Hassan-Kadle Ahmed A. , Ibrahim Abdalla M. , Nyingilili Hamisi S. , Yusuf Abdulkarim A. , Vieira Thállitha S. W. J. , Vieira Rafael F. C. 
Published: December 2019

Abstract
Background
Camel trypanosomiasis or surra is of great concern in Somalia, since the country possesses the largest one-humped camel (Camelus dromedarius) population in the world. Civil war in Somalia has resulted in the destruction of educational, research, economic and social structures, making the country scores very low for most humanitarian indicators. Previous studies on detection of Trypanosoma species in Somali camels have only been performed during the 1990s using standard trypanosome detection methods (STDM). Considering the lack of state-of-the-art knowledge on camel trypanosomiasis in Somalia, the present study aimed to assess the prevalence of Trypanosoma spp. in three districts of Somalia.

Methods
A total of 182 blood samples from C. dromedarius from nomadic and dairy farms were evaluated using STDM, serological (CATT/T. evansi) and molecular (ITS1-PCR) methods.

Results
All samples were negative for Trypanosoma spp. by STDM. A total of 125/182 (68.7%, 95% CI: 61.4–75.3%) camels were seropositive for T. evansi by CATT/T. evansi. Camels reared in nomadic system were more likely to be seropositive for T. evansi than those under dairy production system (OR: 5.6, 95% CI: 2.1–15.2, P = 0.0001). Five out of 182 (2.7%, 95% CI: 0.9–6.3%) camels tested positive for Trypanosoma sp. by ITS1-PCR. Sequencing of the ITS1 region of the Trypanosoma species detected herein revealed that camels were infected with T. evansi and T. simiae.

Conclusions
Trypanosoma evansi is highly prevalent in camels from the Banadir region of Somalia, particularly in nomadic herds. To our knowledge, this is the first study to confirm infections with T. evansi and T. simiae in Somali camels through DNA sequencing. Our data highlight the need for implementation of adequate control measures aiming to reduce the impact on camel production in the country.