bluuebunny/crossref_metadata_2025 huggingface dataset:
ERS guidelines on the diagnosis and treatment of chronic cough in adults and children
Authors: Morice Alyn H. , Millqvist Eva , Bieksiene Kristina , Birring Surinder S. , Dicpinigaitis Peter , Domingo Ribas Christian , Hilton Boon Michele , Kantar Ahmad , Lai Kefang , McGarvey Lorcan , Rigau David , Satia Imran , Smith Jacky , Song Woo-Jung , Tonia Thomy , van den Berg Jan W.K. , van Manen Mirjam J.G. , Zacharasiewicz Angela
Published: September 2019

These guidelines incorporate the recent advances in chronic cough pathophysiology, diagnosis and treatment. The concept of cough hypersensitivity has allowed an umbrella term that explains the exquisite sensitivity of patients to external stimuli such a cold air, perfumes, smoke and bleach. Thus, adults with chronic cough now have a firm physical explanation for their symptoms based on vagal afferent hypersensitivity. Different treatable traits exist with cough variant asthma (CVA)/eosinophilic bronchitis responding to anti-inflammatory treatment and non-acid reflux being treated with promotility agents rather the anti-acid drugs. An alternative antitussive strategy is to reduce hypersensitivity by neuromodulation. Low-dose morphine is highly effective in a subset of patients with cough resistant to other treatments. Gabapentin and pregabalin are also advocated, but in clinical experience they are limited by adverse events. Perhaps the most promising future developments in pharmacotherapy are drugs which tackle neuronal hypersensitivity by blocking excitability of afferent nerves by inhibiting targets such as the ATP receptor (P2X3). Finally, cough suppression therapy when performed by competent practitioners can be highly effective. Children are not small adults and a pursuit of an underlying cause for cough is advocated. Thus, in toddlers, inhalation of a foreign body is common. Persistent bacterial bronchitis is a common and previously unrecognised cause of wet cough in children. Antibiotics (drug, dose and duration need to be determined) can be curative. A paediatric-specific algorithm should be used.
Impact of transition to a subterranean lifestyle on morphological disparity and integration in talpid moles (Mammalia, Talpidae)
Authors: Sansalone Gabriele , Colangelo Paolo , Loy Anna , Raia Pasquale , Wroe Stephen , Piras Paolo
Published: September 2019

Background

Understanding the mechanisms promoting or constraining morphological diversification within clades is a central topic in evolutionary biology. Ecological transitions are of particular interest because of their influence upon the selective forces and factors involved in phenotypic evolution. Here we focused on the humerus and mandibles of talpid moles to test whether the transition to the subterranean lifestyle impacted morphological disparity and phenotypic traits covariation between these two structures.

Results

Our results indicate non-subterranean species occupy a significantly larger portion of the talpid moles morphospace. However, there is no difference between subterranean and non-subterranean moles in terms of the strength and direction of phenotypic integration.

Conclusions

Our study shows that the transition to a subterranean lifestyle significantly reduced morphological variability in talpid moles. However, this reduced disparity was not accompanied by changes in the pattern of traits covariation between the humerus and the mandible, suggesting the presence of strong phylogenetic conservatism within this pattern.
Missense mutations in a transmembrane domain of the Komagataeibacter xylinus BcsA lead to changes in cellulose synthesis
Authors: Salgado Luis , Blank Silvia , Esfahani Reza Alipour Moghadam , Strap Janice L. , Bonetta Dario
Published: September 2019

Background

Cellulose is synthesized by an array of bacterial species. Komagataeibacter xylinus is the best characterized as it produces copious amounts of the polymer extracellularly. Despite many advances in the past decade, the mechanisms underlying cellulose biosynthesis are not completely understood. Elucidation of these mechanisms is essential for efficient cellulose production in industrial applications.

Results

In an effort to gain a better understanding of cellulose biosynthesis and its regulation, cellulose crystallization was investigated in K. xylinus mutants resistant to an inhibitor of cellulose I formation, pellicin. Through the use of forward genetics and site-directed mutagenesis, A449T and A449V mutations in the K. xylinus BcsA protein were found to be important for conferring high levels of pellicin resistance. Phenotypic analysis of the bcsAA449T and bcsAA449V cultures revealed that the mutations affect cellulose synthesis rates and that cellulose crystallinity is affected in wet pellicles but not dry ones.

Conclusions

A449 is located in a predicted transmembrane domain of the BcsA protein suggesting that the structure of the transmembrane domain influences cellulose crystallization either by affecting the translocation of the nascent glucan chain or by allosterically altering protein-protein interactions.
A global picture of family medicine: the view from a WONCA Storybooth
Authors: Cubaka Vincent K. , Dyck Clayton , Dawe Russell , Alghalyini Baraa , Whalen-Browne Molly , Cejas Gabriel , Gibson Christine
Published: September 2019

Background

Family Medicine is a novel discipline in many countries, where the motivation for training and value added to communities is not well-described. Our purpose was to understand the reason behind the choice of Family Medicine as a profession, the impact of Family Medicine on communities, and Family Medicine’s characterizing qualities, as perceived by family doctors around the world.

Methods

One-question video interviews were conducted using an appreciative inquiry approach, with volunteer participants at the 2016 World Organization of Family Doctors conference in Rio de Janeiro. Qualitative data analysis applied the thematic, framework method.

Results

135 family doctors from 55 countries participated in this study. Three overarching themes emerged: 1) key attributes of Family Medicine, 2) core Family Medicine values and 3) shared traits of family doctors. Family Medicine attributes and values were the key expressed motivators to join Family Medicine as a profession and were also among expressed factors that contributed to the impact of Family Medicine globally. Major sub-themes included the principles of comprehensive care, holistic care, continuity of care, patient centeredness, and the patient-provider relationship. Participants emphasized the importance of universal care, human rights, social justice and health equity.

Conclusion

Family doctors around the world shared stories about their profession, presenting a heterogeneous picture of global Family Medicine unified by its attributes and values. These stories may inspire and serve as positive examples for Family Medicine programs, prospective students, advocates and other stakeholders.
Metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with X-linked agammaglobulinemia: a case report
Authors: Li Mingming , Chen Wei , Sun Xiaomeng , Wang Zhipeng , Zou Xun , Wei Hua , Wang Zhan , Chen Wansheng
Published: September 2019

Background

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by germline mutations in the Bruton tyrosine kinase (BTK) gene on X chromosome. These mutations disturb B-cell development, decrease immunoglobulin levels, increase susceptibility to infection or neoplasms, and increase the risk of developing colorectal cancer (CRC). For occasional cases of CRC have been reported in XLA patients, low levels of B lymphocytes and immunoglobulins induced by congenital immune disorder make them more susceptible to drug-related toxicities (DRT). Therefore, gene sequencing, therapeutic drug monitoring and any possible measurement to predict DRT should be considered before determining the course of chemotherapy for XLA patients with CRC.

Case presentation

In this study, we reported a 21-year-old male who developed metastatic CRC in the context of XLA. Since the whole exome sequencing and therapeutic drug monitoring did not reveal any predictive markers of DRT, we applied standard first-line chemotherapy to the patient. However, progressive disease occurred after the fifth treatment cycle. Therefore, the administration of oxaliplatin was changed to irinotecan as second-line therapy. After that, the patient firstly suffered from severe hypocalcemia and eventually died due to metastatic CRC after the eighth treatment cycle. The overall survival time was 7.5 months.

Conclusions

This study reported the first written record of a Chinese XLA patient with metastatic CRC and severe hypocalcemia. Whole exome sequencing and bioinformatic analysis indicated the somatic mutations in ABCA6, C6 and PAX3 genes might contribute to the early-onset and metastasis CRC. Besides, a number of germline mutations in genes related to calcium metabolism (CACNA2D4, CD36, etc.) and the administration of irinotecan were speculated to be the causes of severe hypocalcemia. We therefore suggested that in order to avoid severe DRT, clinicians should take genetic background and therapeutic drug monitoring into consideration while planning chemotherapy treatment for XLA patients with CRC.
Glioma malignancy is linked to interdependent and inverse AMOG and L1 adhesion molecule expression
Authors: Jiang Qiong , Xie Qing , Hu Chengliang , Yang Zhai , Huang Peizhi , Shen Huifan , Schachner Melitta , Zhao Weijiang
Published: September 2019

Background

Gliomas account for the majority of primary human brain tumors and remain a challenging neoplasm for cure due to limited therapeutic options. Cell adhesion molecules play pivotal roles in the growth and progression of glial tumors. Roles of the adhesion molecules on glia (AMOG) and L1CAM (L1) in glioma cells have been shown to correlate with tumorigenesis: Increased expression of L1 and decreased expression of AMOG correlate with degree of malignancy.

Methods

We evaluated the interdependence in expression of these molecules by investigating the role of AMOG in vitro via modulation of L1 expression and analyzing apoptosis and cell senescence of glioma cells.

Results

Immunohistochemical staining of normal human cortical and glioma tissue microarrays demonstrated that AMOG expression was lower in human gliomas compared to normal tissue and is inversely correlated with the degree of malignancy. Moreover, reduction of AMOG expression in human glioblastoma cells elevated L1 expression, which is accompanied by decreased cell apoptosis as well as senescence.

Conclusion

AMOG and L1 interdependently regulate their expression levels not only in U-87 MG cells but also in U251 and SHG44 human glioma cell lines. The capacity of AMOG to reduce L1 expression suggests that methods for increasing AMOG expression may provide a therapeutic choice for the management of glial tumors with high expression of L1.
Alcohol consumption pattern in western Nepal: findings from the COBIN baseline survey
Authors: Adhikari Tara Ballav , Rijal Anupa , Kallestrup Per , Neupane Dinesh
Published: September 2019

Background

Harmful use of alcohol is a global public health problem. Differences in alcohol consumption patterns may add valuable information to the design of public health interventions to prevent excessive use of alcohol, which is yet missing in Nepal. Hence, the purpose of the study is to determine the prevalence, patterns of alcohol consumption and socio-economic correlates of lifetime alcohol consumption and binge drinking in the semi-urban area of Pokhara Municipality.

Methods

The cross-sectional data used in this study were collected as part of the COBIN study to understand alcohol consumption patterns and frequency and to determine correlates of lifetime alcohol consumption and binge drinking in the semi-urban area of Pokhara Municipality, Nepal.

Results

Out of 2815 study participants, 35.6% had ever used alcohol in their lifetime (Male 67.2% and Female 18.9%). Among 571 respondents who drank alcohol within the past 30 days, 77.1% male, and 46.9% female reported binge drinking behaviour. On average, males consumed 8.8 ± 0.3 standard alcohol drinks on one occasion, while females consumed only 4.4 ± 0.3 alcoholic drinks. Male (OR = 16; 95% CI: 12.1–21.1), older adults (OR = 1.5; 95% CI: 1.2–1.7) and people belonging to disadvantaged ethnic group (OR = 6.1; 95% CI: 4.9–6.3) had higher odds of lifetime alcohol consumption than their respective counterparts. Whereas, male (OR = 7.9; 95% CI: 4.3–14.6), having higher educational status and agriculture as the occupation had higher odds of binge drinking.

Conclusion

Alcohol consumption frequency was significantly higher among males than females in Western Nepal. Although national program and policies should recommend reducing alcohol consumption in general, targeted interventions are needed for males aged 45–65 years of age and certain ethnic groups (Dalit and Janajati).
Assessment of status of solid waste management in Asella town, Ethiopia
Authors: Lema Gorfnesh , Mesfun Million Getachew , Eshete Amade , Abdeta Gizachew
Published: September 2019

Background

Improper solid waste management (SWM) is a major public health and environmental concern in the urban areas of many developing countries such as Asella Town. The aim of this study was to assess the status of SWM in Asella town.

Methods

A community-based cross-sectional study design was used to assess the status of improper SWM and associated factors in Asella town. From the total of eight kebeles (smallest administrative unit in Ethiopia) four kebeles were randomly selected using lottery method. The sample size was 413 households. The households were proportionally allocated to each randomly selected kebeles. The data was collected by pretested questionnaire in the local language. Data was entered using statistical software Epi Info version seven and transferred to SPSS version 21. Descriptive data analysis was done to summarize the socioeconomic status of the respondents. Chi-square was used to show the association between the status of solid waste management and different variables. Binary logistic regression was used to determine the potential factors for improper SWM.

Result

332 (82.8%), had improper solid waste management practice. Lack of adequate knowledge about solid waste management and not having access to door to door solid waste collection could have contributed to the reported improper solid waste practice. Participants who didn’t have access to door to door solid waste collection service were about three times more likely to practice improper solid waste management when compared to those who had access (AOR = 2.873, 95 CI (1.565,5.273) P = 0.001).

Conclusion

The study finding showed that, the majority of the residents practiced improper solid waste management. Lack of adequate knowledge about solid waste management and not having access to door to door solid waste collection could have contributed to the reported improper solid waste practice. Therefore, there is a need to enhance the awareness of the community about proper SWM and to improve the door to door solid waste collection service by the town municipality.
Enhancing healthy ecosystems in northern Ghana through eco-friendly farm-based practices: insights from irrigation scheme-types
Authors: Agula Caesar , Mabe Franklin Nantui , Akudugu Mamudu Abunga , Dittoh Saa , Ayambila Sylvester Nsobire , Bawah Ayaga
Published: September 2019

Background

Farming practices vary from farmer to farmer and from place to place depending on a number of factors including the agroclimatic condition, infrastructure (e.g. irrigation facilities) and management mechanisms (private versus state management). These together affect the functioning and sustainability of the ecosystems. For the sustainability of ecosystems, farmers need to employ ecosystem-based farm practices. This paper examines the ecosystem-based farm management practices (EBFMPs) in private and state-managed irrigation schemes. It also analyses the drivers of farmers’ willingness to pay for EBFMPs sustainability. The study employed mixed methods design, using both qualitative and quantitative techniques of data collection through key informant interviews, focus group discussions and semi-structured questionnaires administered to 300 households. The various EBFMPs adopted by farmers were examined and descriptively presented. The Chi-square automatic interaction detector (CHAID) and multiple linear regression were used to assess the predictors of farmers’ willingness to pay for EBFMPs to enhance the health of agroecosystems. Compost application, conservative tilling, conservation of vegetation, mulching, crop rotation, intercropping with legumes, efficient drainage systems and bunding were the EBFMPs captured in this paper.

Results

Farmers in privately-managed irrigation schemes (PIS) more often apply EBFMPs compared with those in state-managed irrigation schemes (SIS). The paper also found that farmers’ willingness to pay to sustain EBFMPs for healthy ecosystems is significantly determined by the type of irrigation scheme they cultivate in (that is, PIS or SIS), their level of education, marital status and perception of soil fertility.

Conclusions

Policy makers, implementers, and other stakeholders need to consider the capacity building of irrigation farmers, especially those in SIS in northern Ghana by educating them on agricultural production and ecosystem nexus to enhance the level of usage and willingness to pay for EBFMPs sustainability.
Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension
Authors: White R. James , Vonk-Noordegraaf Anton , Rosenkranz Stephan , Oudiz Ronald J. , McLaughlin Vallerie V. , Hoeper Marius M. , Grünig Ekkehard , Ghofrani Hossein-Ardeschir , Chakinala Murali M. , Barberà Joan A. , Blair Christiana , Langley Jonathan , Frost Adaani E.
Published: September 2019

Background

Initial combination therapy with ambrisentan and tadalafil reduced the risk of clinical failure events for treatment-naïve participants with pulmonary arterial hypertension (PAH) as compared to monotherapy. Previous studies in PAH have demonstrated greater treatment benefits in more symptomatic participants.

Methods

AMBITION was an event-driven, double-blind study in which participants were randomized 2:1:1 to once-daily initial combination therapy with ambrisentan 10 mg plus tadalafil 40 mg, ambrisentan 10 mg plus placebo, or tadalafil 40 mg plus placebo. In this pre-specified subgroup analysis, we compared the efficacy data between those with functional class (FC) II vs. FC III symptoms at baseline.

Results

This analysis included 500 participants in the previously defined primary analysis set (n = 155 FC II, n = 345 FC III). Comparing combination therapy to pooled monotherapy, the risk of clinical failure events was reduced by 79% (hazard ratio, 0.21 [95% confidence interval: 0.071, 0.63]) for FC II patients and 42% (hazard ratio, 0.58 [95% confidence interval: 0.39, 0.86]) for FC III patients. In a post-hoc analysis, the risk of first hospitalization for worsening PAH was also reduced by combination therapy, particularly for FC II patients (0 combination vs. 11 [14%] pooled monotherapy). Adverse events were frequent but comparable between the subgroups.

Conclusions

Treatment benefit from initial combination therapy appeared at least as great for FC II as for FC III participants. Hospitalizations for worsening PAH were not observed in FC II participants assigned to combination. The present data support an initial combination strategy for newly diagnosed patients even when symptoms are less severe.

Funded by Gilead Sciences, Inc. and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.
Neuroinflammation as a target for treatment of stroke using mesenchymal stem cells and extracellular vesicles
Authors: Dabrowska Sylwia , Andrzejewska Anna , Lukomska Barbara , Janowski Miroslaw
Published: September 2019

Ischemic stroke is the third cause of death in the developed countries and the main reason of severe disability. Brain ischemia leads to the production of damage-associated molecular patterns (DAMPs) by neurons and glial cells which results in astrocyte and microglia activation, pro-inflammatory cytokines and chemokines production, blood-brain barrier (BBB) disruption, infiltration of leukocytes from the peripheral blood into the infarcted area, and further exacerbation of tissue damage. However, some immune cells such as microglia or monocytes are capable to change their phenotype to anti-inflammatory, produce anti-inflammatory cytokines, and protect injured nervous tissue. In this situation, therapies, which will modulate the immune response after brain ischemia, such as transplantation of mesenchymal stem cells (MSCs) are catching interest. Many experimental studies of ischemic stroke revealed that MSCs are able to modulate immune response and act neuroprotective, through stimulation of neurogenesis, oligodendrogenesis, astrogenesis, and angiogenesis. MSCs may also have an ability to replace injured cells, but the release of paracrine factors directly into the environment or via extracellular vesicles (EVs) seems to play the most pronounced role. EVs are membrane structures containing proteins, lipids, and nucleic acids, and they express similar properties as the cells from which they are derived. However, EVs have lower immunogenicity, do not express the risk of vessel blockage, and have the capacity to cross the blood-brain barrier. Experimental studies of ischemic stroke showed that EVs have immunomodulatory and neuroprotective properties; therefore, they can stimulate neurogenesis and angiogenesis. Up to now, 20 clinical trials with MSC transplantation into patients after stroke were performed, from which two concerned on only hemorrhagic stroke and 13 studied only on ischemic stroke. There is no clinical trial with EV injection into patients after brain ischemia so far, but the case with miR-124-enriched EVs administration is planned and probably there will be more clinical studies with EV transplantation in the near future.
Moderate physical exercise improves lymphocyte function in melanoma-bearing mice on a high-fat diet
Authors: dos Santos Cesar Miguel Momesso , Diniz Vinicius Leonardo Sousa , Bachi André Luis Lacerda , dos Santos de Oliveira Laiane Cristina , Ghazal Tamara , Passos Maria Elizabeth Pereira , de Oliveira Heloisa Helena , Murata Gilson , Masi Laureane Nunes , Martins Amanda Roque , Levada-Pires Adriana Cristina , Curi Rui , Hirabara Sandro Massao , Sellitti Donald F. , Pithon-Curi Tania Cristina , Gorjão Renata
Published: September 2019

Background

Obesity can lead to a chronic systemic inflammatory state that increases the risk of cancer development. Therefore, this study aimed to evaluate the alterations in tumor non-infiltrated lymphocytes function and melanoma growth in animals maintained on a high-fat diet and/or moderate physical exercise program in a murine model of melanoma.

Methods

Female mice were randomly divided into eight groups: 1) normolipidic control (N), 2) normolipidic + melanoma (NM), 3) high-fat control (H), 4) high-fat + melanoma (HM), 5) normolipidic control + physical exercise (NE), 6) normolipidic melanoma + physical exercise (NEM), 7) high-fat control + physical exercise (HE), and 8) high-fat melanoma + physical exercise (HEM). After 8 weeks of diet treatment and/or moderate physical exercise protocol, melanoma was initiated by explanting B16F10 cells into one-half of the animals.

Results

Animals fed a high-fat diet presented high-energy consumption (30%) and body weight gain (H and HE vs N and NE, 37%; HM and HEM vs NM and NEM, 73%, respectively), whether or not they carried melanoma explants. Although the tumor growth rate was higher in animals from the HM group than in animals from any other sedentary group, it was reduced by the addition of a physical exercise regimen. We also observed an increase in stimulated peripheral lymphocyte proliferation and a decrease in the T-helper 1 response in the HEM group.

Conclusions

The results of the present study support the hypothesis that altering function of tumor non-infiltrated lymphocytes via exercise-related mechanisms can slow melanoma progression, indicating that the incorporation of a regular practice of moderate-intensity exercises can be a potential strategy for current therapeutic regimens in treating advanced melanoma.
Keeping up with the times: how national public health and governmental organizations communicate about cannabis on Twitter
Authors: van Draanen Jenna , Krishna Tanvi , Tsang Christie , Liu Sam
Published: September 2019

Background

Public health and governmental organizations are expected to provide guidance to the public on emerging health issues in accessible formats. It is, therefore, important to examine how such organizations are discussing cannabis online and the information that is being provided to the public about this increasingly legal and available substance.

Methods

This paper presents a concise thematic analysis of both the volume and content of cannabis-related health information from selected (n = 13) national-level public health and governmental organizations in Canada and the U.S. on Twitter.

Results

There were eight themes identified in Tweets including 1) health-related topics; 2) legalization and legislation; 3) research on cannabis; 4) special populations; 5) driving and cannabis; 6) population issues; 7) medical cannabis, and 8) public health issues. The majority of cannabis-related Tweets from the organizations studied came from relatively few organizations and there were substantial differences between the topics covered by U.S. and Canadian organizations. The organizations studied provided limited information regarding how to use cannabis in ways that will minimize health-related harms.

Conclusions

Authoritative organizations that deal with public health may consider designing timely social media communications with emerging cannabis-related information, to benefit a general public otherwise exposed to primarily pro-cannabis content on Twitter.
A study on fracture lines of the quadrilateral plate based on fracture mapping
Authors: Yang Yun , Zou Chang , Fang Yue
Published: September 2019

Background

Quadrilateral plate fractures are a challenging group of acetabular fractures to manage. However, there is little literature that describes the fracture lines of the quadrilateral plate. The aim of this study was to explore the fracture lines of the quadrilateral plate and relevant clinical significance.

Methods

CT data from a series of acetabular fractures were retrospectively analyzed. According to the X-ray, CT, and operative records of the patients, Judet-Letournel classification was carried out for acetabular fractures involving quadrilateral plate. Then, the fracture maps of different types of acetabular fractures in the quadrilateral plate were drawn. To facilitate the characterization of fracture maps, we defined six basic fracture lines.

Results

The fracture lines of the three types of acetabular fractures (double-column fracture, T-type fracture, and anterior column with posterior hemitransverse fracture) mainly included upper transverse lines and upper oblique lines. Although the fracture lines of posterior wall fracture and anterior column fracture were mainly upper transverse lines, the fracture lines of the former were in a low position. The fracture lines of transverse fracture and transverse with posterior wall fracture were similar, both of which were mainly upper oblique lines. The fracture lines of posterior column fractures mainly included posterior vertical lines.

Conclusions

The fracture lines of different types of acetabular fractures have certain regularity respectively. Observation of the fracture lines of the quadrilateral plate based on fracture mapping can help orthopedic surgeons to enhance the understanding of the Judet-Letournel classification, which may have some significant guidance on the choice of operation approach and the design of internal fixation devices.
Long noncoding RNA GSTM3TV2 upregulates LAT2 and OLR1 by competitively sponging let-7 to promote gemcitabine resistance in pancreatic cancer
Authors: Xiong Guangbing , Liu Chang , Yang Gang , Feng Mengyu , Xu Jianwei , Zhao Fangyu , You Lei , Zhou Li , Zheng Lianfang , Hu Ya , Wang Xiaowo , Zhang Taiping , Zhao Yupei
Published: September 2019

Background

Chemoresistance is one of the main causes of poor prognosis in pancreatic cancer patients. Understanding the mechanisms implicated in chemoresistance of pancreatic cancer is critical to improving patient outcomes. Recent evidences indicate that the long noncoding RNAs (lncRNAs) are involving in chemoresistance of pancreatic cancer. However, the mechanisms of lncRNAs contribute to resistance in pancreatic cancer and remain largely unknown. The objective of this study is to construct a chemoresistance-related lncRNA-associated competing endogenous RNA (ceRNA) network of pancreatic cancer and identify the key lncRNAs in regulating chemoresistance of the network.

Methods

Firstly, lncRNA expression profiling of gemcitabine-resistant pancreatic cancer cells was performed to identify lncRNAs related to chemoresistance by microarray analysis. Secondly, with insights into the mechanism of ceRNA, we used a bioinformatics approach to construct a chemoresistance-related lncRNAs-associated ceRNA network. We then identified the topological key lncRNAs in the ceRNA network and demonstrated its function or mechanism in chemoresistance of pancreatic cancer using molecular biological methods. Further studies evaluated its expression to assess its potential association with survival in patients with pancreatic cancer.

Results

Firstly, we demonstrated that lncRNAs were dysregulated in gemcitabine-resistant pancreatic cancer cells. We then constructed a chemoresistance-related lncRNA-associated ceRNA network and proposed that lncRNA Homo sapiens glutathione S-transferase mu 3, transcript variant 2 and noncoding RNA (GSTM3TV2; NCBI Reference Sequence: NR_024537.1) might act as a key ceRNA to enhance chemoresistance by upregulating L-type amino acid transporter 2 (LAT2) and oxidized low-density lipoprotein receptor 1(OLR1) in pancreatic cancer. Further studies demonstrated that GSTM3TV2, overexpressed in gemcitabine-resistant cells, enhanced the gemcitabine resistance of pancreatic cancer cells in vitro and in vivo. Mechanistically, we identified that GSTM3TV2 upregulated LAT2 and OLR1 by competitively sponging let-7 to promote gemcitabine resistance. In addition, we revealed that the expression levels of GSTM3TV2 were significantly increased in pancreatic cancer tissues and were associated with poor prognosis.

Conclusion

Our results suggest that GSTM3TV2 is a crucial oncogenic regulator involved in chemoresistance and could be a new therapeutic target or prognostic marker in pancreatic cancer.
Medial malleolus: Operative Or Non-operative (MOON) trial protocol - a prospective randomised controlled trial of operative versus non-operative management of associated medial malleolus fractures in unstable fractures of the ankle
Authors: Carter Thomas H. , Oliver William M. , Graham Catriona , Duckworth Andrew D. , White Timothy O.
Published: September 2019

Background

There are limited data reporting the outcome of patients with non-operatively managed medial malleolus fractures compared to those treated surgically in the presence of fibular stabilisation for unstable fractures of the ankle. Conservative management could result in fewer complications, reduced surgical time and lower cost. The purpose of this study is to determine if any difference exists in patient reported and surgical outcomes 1 year after surgery between operative and non-operative treatment of medial malleolar fractures in combination with stabilisation of the lateral malleolus.

Methods/design

This is a single-centre, prospective, randomised controlled trial that aims to randomise 154 participants with an unstable ankle fracture to ‘non-fixation’ (n = 77) or ‘fixation’ (n = 77) of an associated well-reduced medial malleolus fracture following fibular stabilisation. The study will include patients ≥ 16 years of age with a closed bimalleolar or trimalleolar ankle fracture who are able to consent, complete questionnaires in the English language, and complete follow-up over a 1-year period. Randomisation will occur intra-operatively when the medial malleolus fracture is deemed ‘well-reduced’, with 2 mm or less of fluoroscopic displacement. The technique for fixation of both the medial and lateral malleoli is at the discretion of the operating surgeon. Patient-reported, observer-rated, and radiographic assessments will be collected at baseline and then at the following post-operative assessment points: 2 weeks, 6 weeks and 1 year. Postal questionnaire outcome data will be collected at 3 and 6 months. The primary outcome measure will be the Olerud Molander Ankle Score (OMAS) at 1 year following surgery. Secondary outcome measures will include the Manchester-Oxford Foot Questionnaire (MOXFQ), EuroQol-5D (EQ-5D), pain, treatment satisfaction, time to return to activity, operative tourniquet time, and complications.

Discussion

There is only one previous randomised trial comparing non-fixation with fixation of associated medial malleolus fractures but that was limited by the lack of baseline patient-reported outcome data and an inferior sample size. This current prospective trial aims to provide high-quality evidence regarding the requirement for medial malleolar fixation in unstable ankle fractures.

Trial registration

ClinicalTrials.gov,NCT03362229. Registered retrospectively on 5 December 2017.
Commissural axon guidance in the developing spinal cord: from Cajal to the present day
Authors: Comer J. D. , Alvarez S. , Butler S. J. , Kaltschmidt J. A.
Published: September 2019

During neuronal development, the formation of neural circuits requires developing axons to traverse a diverse cellular and molecular environment to establish synaptic contacts with the appropriate postsynaptic partners. Essential to this process is the ability of developing axons to navigate guidance molecules presented by specialized populations of cells. These cells partition the distance traveled by growing axons into shorter intervals by serving as intermediate targets, orchestrating the arrival and departure of axons by providing attractive and repulsive guidance cues. The floor plate in the central nervous system (CNS) is a critical intermediate target during neuronal development, required for the extension of commissural axons across the ventral midline. In this review, we begin by giving a historical overview of the ventral commissure and the evolutionary purpose of decussation. We then review the axon guidance studies that have revealed a diverse assortment of midline guidance cues, as well as genetic and molecular regulatory mechanisms required for coordinating the commissural axon response to these cues. Finally, we examine the contribution of dysfunctional axon guidance to neurological diseases.
Rubber world price transmission to Ivorian producer prices: an analysis in the presence of structural breaks
Authors: Ahoba Mélanie , Gaspart Frédéric
Published: September 2019

This article analyzes the link between world prices and producer prices of rubber in Côte d’Ivoire. Using monthly data from 2006 to 2016, we gave special attention to structural breaks in the data and asymmetry in the transmission process. Empirical results validate the presence of two breaks in the data series, both in 2008 and 2011 corresponding to a general surge in commodity prices. A multivariate threshold vector error correction model (TVECM) allows us to test the presence of asymmetry. The results strongly support the linearity hypothesis againstk-regime TVECM. From there, a linear VECM reveals that changes in rubber world prices are strongly transmitted to Ivorian producer prices. In case of a world price permanent decrease, this will be devastating for small producer incomes, since financial markets are essentially missing in those rural areas and switching costs for perennial crops are huge. Some recommendations are given to prevent such a crisis.
Mesenchymal stem cells‐derived extracellular vesicles in acute respiratory distress syndrome: a review of current literature and potential future treatment options
Authors: Shah Trushil G. , Predescu Dan , Predescu Sanda
Published: September 2019

Acute respiratory distress syndrome (ARDS) is a life‐threatening inflammatory lung condition associated with significant morbidity and mortality. Unfortunately, the current treatment for this disease is mainly supportive. Mesenchymal stem cells (MSCs) due to their immunomodulatory properties are increasingly being studied for the treatment of ARDS and have shown promise in multiple animal studies. The therapeutic effects of MSCs are exerted in part in a paracrine manner by releasing extracellular vesicles (EVs), rather than local engraftment. MSC‐derived EVs are emerging as potential alternatives to MSC therapy in ARDS. In this review, we will introduce EVs and briefly discuss current data on EVs and MSCs in ARDS. We will discuss current literature on the role of MSC‐derived EVs in pathogenesis and treatment of ARDS and their potential as a treatment strategy in the future.
The role of multilateral organizations and governments in advancing social innovation in health care delivery
Authors: Halpaap Beatrice , Peeling Rosanna W. , Bonnici François
Published: September 2019

Background

Despite great medical advances and scientific progress over the past century, one billion people globally still lack access to basic health care services. In the context of the 2030 Agenda for Sustainable Development social innovation models aim to provide effective solutions that bridge the health care delivery gap, address equity and create social value. This commentary highlights the roles of multilateral organizations and governments in creating an enabling environment where social innovations can more effectively integrate into health systems to maximize their impact on beneficiaries.

Main text

The integration of social innovations into health systems is essential to ensure their sustainability and the wide dissemination of their impact. Effective partnerships, strong engagement with and endorsement by governments and communities, regulations, trust and sometimes willingness are key factors to enhance system integration, replication and dissemination of the models. Three examples of social innovations selected by the Social Innovation in Health Initiative illustrate the importance of engaging with governments and communities in order to link, integrate and synergize their efforts. Key challenges that they encountered, and lessons learnt are highlighted. Multilateral organizations and governments increasingly engage in promoting and supporting the development, testing and dissemination of social innovations to address the health care delivery gap. They play an important role in creating an enabling environment. This includes promoting the concept of social innovation in health care delivery, spreading social innovation approach and lessons learnt, fostering partnerships and leveraging resources, convening communities, health system actors and various stakeholders to work together across disciplines and sectors, and nurturing capacity in countries.

Conclusions

Multilateral organizations and local and national governments have a critical role to play in creating an enabling environment where social innovations can flourish. In supporting and disseminating social innovation approach, multilateral organizations and governments have a great opportunity to accelerate Universal Health Coverage and the achievement of the Sustainable Development Goals.
Identifying culturally acceptable cognitive tests for use in remote northern Australia
Authors: Rock Deborah , Price Ian R.
Published: September 2019

Background

A lack of culturally appropriate tests hampers accurate assessment of cognition in remote Australian Aboriginal communities. In Arnhem Land, this study employed a community consultation process to evaluate commonly used Western tests of executive function, memory, attention, and visuospatial function.

Methods

An initial consultation process and a follow-up pilot study resulted in the rejection of some common tests, the development of new tests, and culturally adapted versions of others. In the subsequent 30-person main trial, adult Aboriginal volunteers were examined on nine tests, plus the Kimberly Indigenous Cognitive Assessment screen, and a brief literacy test.

Results

Executive function, memory, and attention tests were found to group separately after an exploratory principal components analysis. Correlations between new tests and similar Kimberly screen items were not significant, but ceiling effects may be relevant. Six of 13 test scores were found to correlate with the literacy measure.

Conclusions

A selection of cognitive tests were identified that Aboriginal people found culturally acceptable and engaging. In particular, Self-Ordered Pointing, Trail-Making, a verbal-switching task, and a new test “Which car?” show promise for further development. This work may contribute to the need for culturally appropriate cognitive testing in Aboriginal communities.
The p75NTR neurotrophin receptor is required to organize the mature neuromuscular synapse by regulating synaptic vesicle availability
Authors: Pérez Viviana , Bermedo-Garcia Francisca , Zelada Diego , Court Felipe A. , Pérez Miguel Ángel , Fuenzalida Marco , Ábrigo Johanna , Cabello-Verrugio Claudio , Moya-Alvarado Guillermo , Tapia Juan Carlos , Valenzuela Vicente , Hetz Claudio , Bronfman Francisca C. , Henríquez Juan Pablo
Published: September 2019

The coordinated movement of organisms relies on efficient nerve-muscle communication at the neuromuscular junction. After peripheral nerve injury or neurodegeneration, motor neurons and Schwann cells increase the expression of the p75NTRpan-neurotrophin receptor. Even though p75NTRtargeting has emerged as a promising therapeutic strategy to delay peripheral neuronal damage progression, the effects of long-term p75NTRinhibition at the mature neuromuscular junction have not been elucidated. We performed quantitative neuroanathomical analyses of the neuromuscular junction in p75NTRnull mice by laser confocal and electron microscopy, which were complemented with electromyography, locomotor tests, and pharmacological intervention studies. Mature neuromuscular synapses of p75NTRnull mice show impaired postsynaptic organization and ultrastructural complexity, which correlate with altered synaptic function at the levels of nerve activity-induced muscle responses, muscle fiber structure, force production, and locomotor performance. Our results on primary myotubes and denervated muscles indicate that muscle-derived p75NTRdoes not play a major role on postsynaptic organization. In turn, motor axon terminals of p75NTRnull mice display a strong reduction in the number of synaptic vesicles and active zones. According to the observed pre and postsynaptic defects, pharmacological acetylcholinesterase inhibition rescued nerve-dependent muscle response and force production in p75NTRnull mice. Our findings revealing that p75NTRis required to organize mature neuromuscular junctions contribute to a comprehensive view of the possible effects caused by therapeutic attempts to target p75NTR.
Evaluating the performance of sentence level features and domain sensitive features of product reviews on supervised sentiment analysis tasks
Authors: Rintyarna Bagus Setya , Sarno Riyanarto , Fatichah Chastine
Published: September 2019

With the popularity of e-commerce, posting online product reviews expressing customer’s sentiment or opinion towards products has grown exponentially. Sentiment analysis is a computational method that plays an essential role in automating the extraction of subjective information i.e. customer’s sentiment or opinion from online product reviews. Two approaches commonly used in Sentiment analysis tasks are supervised approaches and lexicon-based approaches. In supervised approaches, Sentiment analysis is seen as a text classification task. The result depends not only on the robustness of the machine learning algorithm but also on the utilized features. Bag-of-word is a common utilized features. As a statistical feature, bag-of-word does not take into account semantic of words. Previous research has indicated the potential of semantic in supervised SA task. To augment the result of sentiment analysis, this paper proposes a method to extract text features named sentence level features (SLF) and domain sensitive features (DSF) which take into account semantic of words in both sentence level and domain level of product reviews. A word sense disambiguation based method was adapted to extract SLF. For every similarity employed in generating SLF, the SentiCircle-based method was enhanced to generate DSF. Results of the experiments indicated that our proposed semantic features i.e. SLF and SLF + DSF favorably increase the performance of supervised sentiment analysis on product reviews.
Utility of diffusion-weighted and contrast-enhanced magnetic resonance imaging in diagnosing and differentiating between high- and low-grade uterine endometrial stromal sarcoma
Authors: Huang Yen-Ling , Ueng Shir-Hwa , Chen Kueian , Huang Yu-Ting , Lu Hsin-Ying , Ng Koon-Kwan , Chang Ting-Chang , Lai Chyong-Huey , Lin Gigin
Published: September 2019

Background

Endometrial stromal sarcoma (ESS) is a rare uterine malignancy that features different prognoses for its high- and low-grade subtypes. We investigated the diagnostic accuracy of magnetic resonance (MR) imaging in diagnosing and differentiating between high- and low-grade ESS.

Methods

We retrospectively reviewed the preoperative pelvic MR images of consecutive patients who received histologically confirmed diagnoses of high-grade ESS (n = 11) and low-grade ESS (n = 9) and T2-hyperintense leiomyoma (n = 16). Two radiologists independently evaluated imaging features in T1-, T2-, and diffusion-weighted and contrast-enhanced MR images. Statistical analysis included Mann-Whitney tests and Fisher’s exact test, with sensitivity, specificity and diagnostic accuracy of imaging features.

Results

High-grade ESS was associated with significantly more extensive necrosis and hemorrhage and distinct feather-like enhancement compared with low-grade ESS (P < .05 for all). The feather-like enhancement pattern yielded a diagnostic accuracy of 95%, sensitivity of 91%, and specificity of 100% in differentiating high-grade from low-grade ESS. This imaging characteristic was significantly superior to the necrosis (80%, P = .033) or hemorrhage (75%, P = .007). Both high- and low-grade ESS demonstrated T2 hypointense bands, marginal nodules, intratumoral nodules, and worm-like intra-myometrial nodules, and their tumor apparent diffusion coefficient (ADC) values were significantly lower than those of T2-hyperintense leiomyomas (P < .001).

Conclusions

Diffusion-weighted MR imaging is useful in diagnosing ESS against T2-hyperintense leiomyomas, and contrast enhancement aids in further differentiating between high- and low-grade ESS.