bluuebunny/crossref_metadata_2025 huggingface dataset:
The content of patient counseling about interchangeable medicines and generic substitution in Finnish community pharmacies - a survey of dispensers
Authors: Rainio Riikka , Ahonen Riitta , Timonen Johanna
Published: December 2019

Background

Generic substitution aims to increase the use of more affordable generic preparations and restrain the growth of medicine expenditures. Pharmaceutical staff plays an important role in generic substitution by implementing substitution and counseling customers. The aim of this study was to explore how Finnish dispensers inform pharmacy customers about interchangeable medicines and generic substitution and what customers ask dispensers about generic substitution and the reference price system.

Methods

A questionnaire was sent to a random sample of dispensers (n = 1054) working in community pharmacies in spring 2018. The data was analyzed using frequencies, percentages and the Chi-square test and Fisher’s exact test. The open-ended questions were analyzed first using inductive content analysis and later with the quantitative methods mentioned above.

Results

The final study material consisted of 498 questionnaires (response rate 51%). The main topics dispensers always informed customers about were the physician’s record in the prescription not to substitute the medicine (69%) and that the prescribed or purchased interchangeable medicine did not belong in the reference price band (59%). Topics mentioned often by dispensers dealt with customer’s chance to choose their medicine from among several alternative products (68%) and the manufacturer of the interchangeable medicines (66%). Differences in appearance (33%) or in composition (28%) of interchangeable products were the most common topics mentioned only when the customer asked about them. Of the respondents 17.6% always and 51.4% often informed the customer about the least expensive interchangeable product at the point of dispensing. Customers’ questions about the generic substitution and reference price system most commonly (82.4%) concerned the similarity of interchangeable medicines.

Conclusions

Finnish dispensers provide customers with a wide range of information about different subjects when dispensing interchangeable medicines. Patient counseling generally meets the legislative requirements, except for price counseling. In future, information about generic substitution and interchangeable medicines should continuously be provided to customers both at pharmacies and elsewhere, e.g. through educational campaigns.
A comparative analysis of health surveillance strategies for administrative video display terminal employees
Authors: Gerassis Saki , Abad Alberto , Taboada Javier , Saavedra Ángeles , Giráldez Eduardo
Published: December 2019

Background

The objective of this study was to develop a strategy to optimize medical health surveillance protocols for administrative employees using video display terminals (VDTs). A total of 2453 medical examinations were analysed for VDT users in various sectors. From these data, using Bayesian statistics we inferred which factors were most relevant to medical diagnosis of the main disorders affecting VDT users. This information was used to build an influence diagram to evaluate the time and monetary costs associated with each diagnostic test and define an optimal protocol strategy based on occupational risks.

Results

Musculoskeletal and ophthalmological diseases were identified as the most frequent disorders among VDT users. The Bayesian network inferred age, sleep quality, activity level, smoking and the consumption of alcohol as risk factors. The blood count was the most costly test (5.23 USD/employee) and the second most costly test in time terms (4 min/employee), yet is a diagnostic test that has little influence on the medical decision regarding an employee’s capacity to perform their job.

Conclusions

Current occupational health surveillance protocols for VDT users may lead to expenditure that is 54% greater than necessary. For many employees and employers, failure to perform a wide range of medical tests for occupational health surveillance purposes is subjectively perceived as a threat to health. Awareness needs to be raised of the appropriate role of different health areas, so as to optimize diagnostic efficiency on the basis of greater flexibility.
Pioglitazone prevents cholesterol gallstone formation through the regulation of cholesterol homeostasis in guinea pigs with a lithogenic diet
Authors: Han Tao , Lv Yangge , Wang Shijia , Hu Tao , Hong Hao , Fu Zan
Published: December 2019

Background

The cholesterol gallstones diseases (CGD) is highly correlated with metabolic syndrome and type 2 diabetes. The present study aimed to investigate preventive effects of pioglitazone (PIO), an antidiabetic drug, on the CGD in guinea pigs fed with a lithogenic diet (LD).

Methods

The guinea pigs were fed with the LD for 8 weeks. All guinea pigs were grouped as follows: low fat diet; LD; LD plus PIO (4 mg/kg); LD plus PIO (8 mg/kg); LD plus ezetimibe (EZE) (2 mg/kg). Gallbladder stones were observed using microscopy. The profile of biliary composition, and blood glucose, insulin and lipid were analyzed. The liver or ileum was harvested for determinations of hydroxyl-methyl-glutaryl-CoA reductase (HMGCR), sterol regulatory element-binding proteins 2 (SREBP2), 7α-hydroxylase (CYP7A1), adenosine triphosphate-binding cassette (ABC) sterol transporters G5 and G8 (ABCG5, ABCG8), bile salt export pump (BSEP), Niemann-Pick C1-Like 1 (NPC1L1) and acetyl-coenzyme A cholesterol acyltransferase (ACAT2) by Western blot. The gallbladders were used for histological examination.

Results

The LD successfully induced gallstone. Both pioglitazone and ezetimibe prevented gallstone formation, as well as hepatic and cholecystic damages. Pioglitazone significantly decreased HMGCR and SREBP2, but increased CYP7A1, ABCG5, ABCG8, and BSEP in the liver. Pioglitazone also remarkably decreased NPC1L1 and ACAT2, while increased ABCG5/8 in the intestine. The beneficial alterations of cholesterol and bile acids in the bile, as well as profile of glucose, insulin and lipid in the blood were found in the guinea pigs treated with pioglitazone.

Conclusion

Pioglitazone has a noticeable benefit towards the CGD, which is involved in changes of synthesis, transformation, absorption, and transportation of cholesterol.
The mediating role of sleep quality in the association between nocturia and health-related quality of life
Authors: Choi Edmond Pui Hang , Wan Eric Yuk Fai , Kwok Jojo Yan Yan , Chin Weng Yee , Lam Cindy Lo Kuen
Published: December 2019

Background

Even though the negative impacts of nocturia on sleep quality and health-related quality of life (HRQOL) have been documented in previous research, their interrelationship has been poorly studied. This study aimed to explore whether nocturia would affect sleep quality, which in turn affects HRQOL.

Methods

Participants aged 40 and above were randomly recruited from a Hong Kong public primary care clinic. Participants were asked to report the average number of nocturia (waking up at night to void) pisodes per night over a 1-month period. The Pittsburgh Sleep Quality Index (PSQI) and the 12-Item Short Form Health Survey version 2 (SF-12 v2) were administered. The mediation analysis was tested using multistage regression approach and bootstrap method.

Results

Of the 500 subjects who completed the survey, 31.2% reported symptomatic nocturia (having ≥2 nocturia episodes per night), and 60.4% experienced poor sleep quality (a PSQI global score > 5). Respondents with symptomatic nocturia had a poorer HRQOL in the domains of physical functioning (PF), role physical (RP) and social functioning (SF), general health (GH), vitality (VT) and physical component summary (PCS) of the SF-12 v2 than those without. Compared with the respondents without poor sleep quality, those with poor sleep quality had poorer HRQOL across all domains and summaries of the SF-12 v2. Mediation analysis found that sleep quality fully mediated the association between nocturia and the PF, RP and SF domains of the SF-12 v2, respectively, and partially mediated the association between nocturia and the GH, VT and PCS domains of the SF-12 v2, respectively.

Conclusions

We found that sleep quality mediated the association between nocturia and HRQOL. To enhance the HRQOL of patients with nocturia, clinicians should not only focus on nocturia symptoms, but also on their sleep quality.
TGFβRI antagonist inhibits HIV-1 Nef-induced CC chemokine family ligand 2 (CCL2) in the brain and prevents spatial learning impairment
Authors: Chompre Gladys , Martinez-Orengo Neysha , Cruz Myrella , Porter James T. , Noel Richard J.
Published: December 2019

Background

HIV-1–associated neurocognitive disorders (HAND) progression is related to continued inflammation despite undetectable viral loads and may be caused by early viral proteins expressed by latently infected cells. Astrocytes represent an HIV reservoir in the brain where the early viral neurotoxin negative factor (Nef) is produced. We previously demonstrated that astrocytic expression of Nef in the hippocampus of rats causes inflammation, macrophage infiltration, and memory impairment. Since these processes are affected by TGFβ signaling pathways, and TGFβ-1 is found at higher levels in the central nervous system of HIV-1+ individuals and is released by astrocytes, we hypothesized a role for TGFβ-1 in our model of Nef neurotoxicity.

Methods

To test this hypothesis, we compared cytokine gene expression by cultured astrocytes expressing Nef or green fluorescent protein. To determine the role of Nef and a TGFβRI inhibitor on memory and learning, we infused astrocytes expressing Nef into the hippocampus of rats and then treated them daily with an oral dose of SD208 (10 mg/kg) or placebo for 7 days. During this time, locomotor activity was recorded in an open field and spatial learning tested in the novel location recognition paradigm. Postmortem tissue analyses of inflammatory and signaling molecules were conducted using immunohistochemistry and immunofluorescence.

Results

TGFβ-1 was induced in cultures expressing Nef at 24 h followed by CCL2 induction which was prevented by blocking TGFβRI with SD208 (competitive inhibitor). Interestingly, Nef seems to change the TGFβRI localization as suggested by the distribution of the immunoreactivity. Nef caused a deficit in spatial learning that was recovered upon co-administration of SD208. Brain tissue from Nef-treated rats given SD208 showed reduced CCL2, phospho-SMAD2, cluster of differentiation 163 (CD163), and GFAP immunoreactivity compared to the placebo group.

Conclusions

Consistent with our previous findings, rats treated with Nef showed deficits in spatial learning and memory in the novel location recognition task. In contrast, rats treated with Nef + SD208 showed better spatial learning suggesting that Nef disrupts memory formation in a TGFβ-1-dependent manner. The TGFβRI inhibitor further reduced the induction of inflammation by Nef which was concomitant with decreased TGFβ signaling. Our findings suggest that TGFβ-1 signaling is an intriguing target to reduce neuroHIV.
Process evaluation of a complex intervention to optimize quality of prescribing in nursing homes (COME-ON study)
Authors: Anrys Pauline , Strauven Goedele , Roussel Sandrine , Vande Ginste Marie , De Lepeleire Jan , Foulon Veerle , Spinewine Anne
Published: December 2019

Background

The COME-ON study was a cluster-controlled trial of a complex intervention that consisted of a blended training program, local interdisciplinary meetings, and interdisciplinary case conferences in Belgian nursing homes. The intervention was associated with significant improvements in the appropriateness of prescribing. The aims of this study were to describe the implementation of the intervention and to explore the experiences of participants, for the purpose of identifying factors associated with implementation and perceived impact and to draw lessons for future implementation.

Methods

We performed a mixed-method process evaluation. Questionnaires and reports were used to collect quantitative data on implementation and experiences from the 24 NHs and participating healthcare professionals (coordinating physicians, general practitioners, pharmacists, and nurses) in the intervention group. Multidisciplinary focus groups focusing on factors associated with implementation and perceived impact were conducted in 11 NHs.

Results

Overall, the rate of implementation and the satisfaction of participants were good, despite some variability between NHs and HCPs. Although perceived impact on nursing home residents varied, most participants perceived a positive impact for themselves. Factors associated with implementation and perceived impact were identified at different levels: intervention, healthcare professionals, organization, and external context. The interdisciplinary and face-to-face approaches were recognized as key elements for the success of the intervention, despite organizational constraints. The attitude of general practitioners was identified both as a barrier to and a facilitator for implementation and its success. The professional role and competency of the pharmacist influenced perceived impact. The pre-existing relationships between HCPs and the presence of a leader facilitated implementation and perceived impact. Remuneration was deemed necessary for the study and for future implementation.

Conclusions

Overall, the intervention, and more specifically its interdisciplinary aspect, was well implemented and appreciated by HCPs. This probably contributed to the positive effect on the appropriateness of prescribing. Future implementation must take into account the various factors found to affect implementation and perceived impact, in order to maximize effect and sustainability.

Trial registration

Current Controlled Trials ISRCTN66138978; registered 18 November 2015, retrospectively registered, https://www.isrctn.com/ISRCTN66138978
A novel approach to Verify air gap and SSD for proton radiotherapy using surface imaging
Authors: Wang Xiao , Ma Chi , Davis Rihan , Parikh Rahul R. , Jabbour Salma K. , Haffty Bruce G. , Yue Ning J. , Nie Ke , Zhang Yin
Published: December 2019

Purpose

To develop a novel approach to accurately verify patient set up in proton radiotherapy, especially for the verification of the nozzle – body surface air gap and source-to-skin distance (SSD), the consistency and accuracy of which is extremely important in proton treatment.

Methods

Patient body surfaces can be captured and monitored with the optical surface imaging system during radiation treatment for improved intrafraction accuracy. An in-house software package was developed to reconstruct the patient body surface in the treatment position from the optical surface imaging reference capture and to calculate the corresponding nozzle – body surface air gap and SSD. To validate this method, a mannequin was scanned on a CT simulator and proton plans were generated for a Mevion S250 Proton machine with 20 gantry/couch angle combinations, as well as two different snout sizes, in the Varian Eclipse Treatment Planning Systems (TPS). The surface generated in the TPS from the CT scan was imported into the optical imaging system as an RT Structure for the purpose of validating and establishing a benchmark for ground truth comparison. The optical imaging surface reference capture was acquired at the treatment setup position after orthogonal kV imaging to confirm the positioning. The air gaps and SSDs calculated with the developed method from the surface captured at the treatment setup position (VRT surface) and the CT based surface imported from the TPS were compared to those calculated in TPS. The same approach was also applied to 14 clinical treatment fields for 10 patients to further validate the methodology.

Results

The air gaps and SSDs calculated from our program agreed well with the corresponding values derived from the TPS. For the phantom results, using the CT surface, the absolute differences in the air gap were 0.45 mm ± 0.33 mm for the small snout, and 0.51 mm ± 0.49 mm for the large snout, and the absolute differences in SSD were 0.68 mm ± 0.42 mm regardless of snout size. Using the VRT surface, the absolute differences in air gap were 1.17 mm ± 1.17 mm and 2.1 mm ± 3.09 mm for the small and large snouts, respectively, and the absolute differences in SSD were 0.81 mm ± 0.45 mm. Similarly, for patient data, using the CT surface, the absolute differences in air gap were 0.42 mm ± 0.49 mm, and the absolute differences in SSD were 1.92 mm ± 1.4 mm. Using the VRT surface, the absolute differences in the air gap were 2.35 mm ± 2.3 mm, and the absolute differences in SSD were 2.7 mm ± 2.17 mm.

Conclusion

These results showed the feasibility and robustness of using an optical surface imaging approach to conveniently determine the air gap and SSD in proton treatment, providing an accurate and efficient way to confirm the target depth at treatment.
The radiological outcomes of one-stage posterior-only hemivertebra resection and short segmental fusion for lumbosacral hemivertebra: a minimum of 5 years of follow-up
Authors: Wang Yu , Liu Zhen , Du Changzhi , Shi Benlong , Sun Xu , Wang Bin , Zhu Zezhang , Qiu Yong
Published: December 2019

Background

Previous studies have reported favorable short-term outcomes after posterior-only hemivertebra resection and short fusion in patients with LSHV. However, there is a paucity of data evaluating the long-term outcomes following this procedure. The aim of the study is to evaluate the radiological outcomes following posterior-only hemivertebra resection and short fusion for the treatment of congenital scoliosis (CS) secondary to lumbosacral hemivertebra (LSHV) with a minimum of a 5-year follow-up.

Methods

A total of 23 patients treated with one-stage posterior-only LSHV resection and short fusion with a minimum of a 5-year follow-up were reviewed. Radiographic parameters including the Cobb angles of the lumbosacral curve and compensatory curve, the upper instrumented vertebra (UIV) tilt, and trunk shift were measured. The complications were recorded accordingly.

Results

The mean duration of follow-up was 88.6 ± 28.5 months, and the average age at surgery was 7.8 ± 3.5 years. Fusion levels averaged 3.0 ± 0.7 segments. The lumbosacral curve was corrected from 30.7 ± 10.4° to 6.7 ± 7.1° after surgery (P < 0.001), 7.3 ± 6.1° 2 years after surgery, and 8.1 ± 7.0° at the last follow-up. The compensatory curve was spontaneously corrected from 23.7 ± 9.4° before surgery to 8.3 ± 5.2° after surgery (P < 0.001). However, the angle slightly increased to 9.0 ± 4.8° 2 years after surgery and to 9.6 ± 6.4° at the last follow-up. Trunk shift was improved from 27.3 ± 8.6 mm before surgery to 11.7 ± 9.4 mm after surgery, and it decreased to 10.8 ± 8.2 mm 2 years after surgery and 10.4 ± 8.8 mm at the last follow-up. One patient experienced transient neurologic deficits after surgery. One patient was observed to have screw loosening at 1-year follow-up and received revision surgery.

Conclusion

One-stage posterior-only hemivertebra resection with short fusion is an effective procedure for LSHV, and the correction can be well maintained during longitudinal follow-up. Great attention should be paid to the restoration of lumbosacral horizontalization.
Negative pressure wound therapy for closed incisions in orthopedic trauma surgery: a meta-analysis
Authors: Wang Cong , Zhang Yiwen , Qu Hao
Published: December 2019

Background

This meta-analysis was performed to determine the efficacy of negative pressure wound therapy (NPWT) versus conventional wound dressings for closed incisions in orthopedic trauma surgery.

Methods

A systematic search was performed in PubMed, Embase, and the Cochrane Library databases. The outcome measures included deep surgical site infection (SSI), superficial SSI; wound dehiscence and length of hospital stay. Cochrane collaboration’s tool and the Newcastle–Ottawa Scale (NOS) were used to evaluate literature qualities. Meta-analysis was performed using RevMan 5.3 software.

Results

A total of 6 studies including 2 randomized controlled trials (RCTs) and 4 cohort studies met our inclusion criteria. NPWT resulted in a significantly lower incidence of deep SSI, superficial SSI, and wound dehiscence than conventional wound dressings. However, no statistically significant difference was found in the length of hospital stay.

Conclusions

NPWT appeared to be an efficient alternative to help prevent SSIs and wound dehiscence on closed incisions in orthopedic trauma surgery. Rational use of NWPT should be based on the presence of patient’s condition and risk factors.
Outcomes of 4 years of molecular genetic diagnosis on a panel of genes involved in premature aging syndromes, including laminopathies and related disorders
Authors: Grelet Maude , Blanck Véronique , Sigaudy Sabine , Philip Nicole , Giuliano Fabienne , Khachnaoui Khaoula , Morel Godelieve , Grotto Sarah , Sophie Julia , Poirsier Céline , Lespinasse James , Alric Laurent , Calvas Patrick , Chalhoub Gihane , Layet Valérie , Molin Arnaud , Colson Cindy , Marsili Luisa , Edery Patrick , Lévy Nicolas , De Sandre-Giovannoli Annachiara
Published: December 2019

Background

Segmental progeroid syndromes are a heterogeneous group of rare and often severe genetic disorders that have been studied since the twentieth century. These progeroid syndromes are defined as segmental because only some of the features observed during natural aging are accelerated.

Methods

Since 2015, the Molecular Genetics Laboratory in Marseille La Timone Hospital proposes molecular diagnosis of premature aging syndromes including laminopathies and related disorders upon NGS sequencing of a panel of 82 genes involved in these syndromes.

We analyzed the results obtained in 4 years on 66 patients issued from France and abroad.

Results

Globally, pathogenic or likely pathogenic variants (ACMG class 5 or 4) were identified in about 1/4 of the cases; among these, 9 pathogenic variants were novel. On the other hand, the diagnostic yield of our panel was over 60% when the patients were addressed upon a nosologically specific clinical suspicion, excepted for connective tissue disorders, for which clinical diagnosis may be more challenging. Prenatal testing was proposed to 3 families. We additionally detected 16 variants of uncertain significance and reclassified 3 of them as benign upon segregation analysis in first degree relatives.

Conclusions

High throughput sequencing using the Laminopathies/ Premature Aging disorders panel allowed molecular diagnosis of rare disorders associated with premature aging features and genetic counseling for families, representing an interesting first-level analysis before whole genome sequencing may be proposed, as a future second step, by the National high throughput sequencing platforms (“Medicine France Genomics 2025” Plan), in families without molecular diagnosis.
Systematic analysis of expression signatures of neuronal subpopulations in the VTA
Authors: Kim Hyun Jin , Kim Minhyung , Kang Byeongsoo , Yun Soyeon , Ryeo Shin Eun , Hwang Daehee , Kim Joung-Hun
Published: December 2019

Gene expression profiling across various brain areas at the single-cell resolution enables the identification of molecular markers of neuronal subpopulations and comprehensive characterization of their functional roles. Despite the scientific importance and experimental versatility, systematic methods to analyze such data have not been established yet. To this end, we developed a statistical approach based on in situ hybridization data in the Allen Brain Atlas and thereby identified specific genes for each type of neuron in the ventral tegmental area (VTA). This approach also allowed us to demarcate subregions within the VTA comprising specific neuronal subpopulations. We further identified WW domain-containing oxidoreductase as a molecular marker of a population of VTA neurons that co-express tyrosine hydroxylase and vesicular glutamate transporter 2, and confirmed their region-specific distribution by immunohistochemistry. The results demonstrate the utility of our analytical approach for uncovering expression signatures representing specific cell types and neuronal subpopulations enriched in a given brain area.
The cost-effectiveness of upfront point-of-care testing in the emergency department: a secondary analysis of a randomised, controlled trial
Authors: Goldstein Lara Nicole , Wells Mike , Vincent-Lambert Craig
Published: December 2019

Background

Time-saving is constantly sought after in the Emergency Department (ED), and Point-of-Care (POC) testing has been shown to be an effective time-saving intervention. However, when direct costs are compared, these tests commonly appear to be cost-prohibitive. Economic viability may become apparent when the time-saving is translated into financial benefits from staffing, time- and cost-saving. The purpose of this study was to evaluate the cost-effectiveness of diagnostic investigations utilised prior to medical contact for ED patients with common medical complaints.

Methods

This was a secondary analysis of data from a prospective, randomised, controlled trial in order to assess the cost-effectiveness of upfront, POC testing. Eleven combinations of POC equivalents of commonly-used special investigations (blood tests (i-STAT and complete blood count (CBC)), electrocardiograms (ECGs) and x-rays (LODOX® (Low Dose X-ray)) were evaluated compared to the standard ED pathway with traditional diagnostic tests. The economic viability of each permutation was assessed using the Incremental Cost Effectiveness Ratio and Cost-Effectiveness Acceptability Curves. Expenses related to the POC test implementation were compared to the control group while taking staffing costs and time-saving into account.

Results

There were 897 medical patients randomised to receive various combinations of POC tests. The most cost-effective combination was the i-STAT+CBC permutation which, based on the time saving, would ultimately save money if implemented. All LODOX®-containing permutations were costlier but still saved time. Non-LODOX® permutations were virtually 100% cost-effective if an additional cost of US$50 per patient was considered acceptable. Higher staffing costs would make using POC testing even more economical.

Conclusions

In certain combinations, upfront, POC testing is more cost-effective than standard diagnostic testing for common ED undifferentiated medical presentations – the most economical POC test combination being the i-STAT + CBC. Upfront POC testing in the ED has the potential to not only save time but also to save money.

Trial registration

ClinicalTrials.gov:NCT03102216.
A randomized trial of a specialist palliative care intervention for patients undergoing surgery for cancer: rationale and design of the Surgery for Cancer with Option of Palliative Care Expert (SCOPE) Trial
Authors: Shinall Myrick C. , Hoskins Aimee , Hawkins Alexander T. , Bailey Christina , Brown Alaina , Agarwal Rajiv , Duggan Maria C. , Beskow Laura M. , Periyakoil Vyjeyanthi S. , Penson David F. , Jarrett Ryan T. , Chandrasekhar Rameela , Ely E. Wesley
Published: December 2019

Background

In medical oncology settings, early specialist palliative care interventions have demonstrated improvements in patient quality of life and survival compared with usual oncologic care. However, the effect of early specialist palliative care interventions in surgical oncology settings is not well studied.

Methods

The Surgery for Cancer with Option for Palliative Care Expert (SCOPE) Trial is a single-center, prospective, single-blind, randomized controlled trial of a specialist palliative care intervention for cancer patients undergoing non-palliative surgery. It will enroll 236 patients scheduled for major abdominal operations for malignancy, who will be randomized 1:1 at enrollment to receive usual care (control arm) or specialist palliative care consultation (intervention arm). Intervention arm patients will receive consultations from a palliative care specialist (physician or nurse practitioner) preoperatively and postoperatively. The primary outcome is physical and functional wellbeing at 90 days postoperatively. Secondary outcomes are quality of life at 90 days postoperatively, posttraumatic stress disorder symptoms at 180 days postoperatively, days alive at home without an emergency room visit in the first 90 postoperative days, and overall survival at 1 year postoperatively. Participants will be followed for 3 years after surgery for exploratory analyses of their ongoing quality of life, healthcare utilization, and mortality.

Discussion

SCOPE is an ongoing randomized controlled trial evaluating specialist palliative care interventions for cancer patients undergoing non-palliative oncologic surgery. Findings from the study will inform ways to identify and improve care of surgical patients who will likely benefit from specialist palliative care services.

Trial registration

ClinicalTrials.gov Identifier:NCT03436290

First Registered: 16 February 2018

Enrollment Began: 1 March 2018

Last Update: 20 December 2018
Proposition of a novel animal model of systemic sclerosis induced by type V collagen in C57BL/6 mice that reproduces fibrosis, vasculopathy and autoimmunity
Authors: Teodoro Walcy Rosolia , de Jesus Queiroz Zelita Aparecida , dos Santos Lais Araujo , Catanozi Sergio , dos Santos Filho Antonio , Bueno Cleonice , Vendramini Margarete B. G. , Fernezlian Sandra de Morais , Eher Esmeralda M. , Sampaio-Barros Percival D. , Pasoto Sandra Gofinet , Lopes Fernanda Degobbi T. Q. S. , Velosa Ana Paula Pereira , Capelozzi Vera Luiza
Published: December 2019

Background

Type V collagen (Col V) has the potential to become an autoantigen and has been associated with the pathogenesis of systemic sclerosis (SSc). We characterized serological, functional, and histopathological features of the skin and lung in a novel SSc murine model induced by Col V immunization.

Methods

Female C57BL/6 mice (n = 19, IMU-COLV) were subcutaneously immunized with two doses of Col V (125 μg) emulsified in complete Freund adjuvant, followed by two intramuscular boosters. The control group (n = 19) did not receive Col V. After 120 days, we examined the respiratory mechanics, serum autoantibodies, and vascular manifestations of the mice. The skin and lung inflammatory processes and the collagen gene/protein expressions were analyzed.

Results

Vascular manifestations were characterized by endothelial cell activity and apoptosis, as shown by the increased expression of VEGF, endothelin-1, and caspase-3 in endothelial cells. The IMU-COLV mice presented with increased tissue elastance and a nonspecific interstitial pneumonia (NSIP) histologic pattern in the lung, combined with the thickening of the small and medium intrapulmonary arteries, increased Col V fibers, and increased COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2 gene expression. The skin of the IMU-COLV mice showed thickness, epidermal rectification, decreased papillary dermis, atrophied appendages, and increased collagen, COL5A1, and COL5A2 gene expression. Anti-collagen III and IV and ANA antibodies were detected in the sera of the IMU-COLV mice.

Conclusion

We demonstrated that cutaneous, vascular, and pulmonary remodeling are mimicked in the Col V-induced SSc mouse model, which thus represents a suitable preclinical model to study the mechanisms and therapeutic approaches for SSc.
Dataset for file fragment classification of textual file formats
Authors: Mansouri Hanis Fatemeh , Teimouri Mehdi
Published: December 2019

Objectives

Classification of textual file formats is a topic of interest in network forensics. There are a few publicly available datasets of files with textual formats. Therewith, there is no public dataset for file fragments of textual file formats. So, a big research challenge in file fragment classification of textual file formats is to compare the performance of the developed methods over the same datasets.

Data description

In this study, we present a dataset that contains file fragments of five textual file formats: Binary file format for Word 97–Word 2003, Microsoft Word open XML format, portable document format, rich text file, and standard text document. This dataset contains the file fragments in three different languages: English, Persian, and Chinese. For each pair of file format and language, 1500 file fragments are provided. So, the dataset of file fragments contains 22,500 file fragments.
The phenotypic variations of multi-locus imprinting disturbances associated with maternal-effect variants of NLRP5 range from overt imprinting disorder to apparently healthy phenotype
Authors: Sparago Angela , Verma Ankit , Patricelli Maria Grazia , Pignata Laura , Russo Silvia , Calzari Luciano , De Francesco Naomi , Del Prete Rosita , Palumbo Orazio , Carella Massimo , Mackay Deborah J. G. , Rezwan Faisal I. , Angelini Claudia , Cerrato Flavia , Cubellis Maria Vittoria , Riccio Andrea
Published: December 2019

Background

A subset of individuals affected by imprinting disorders displays multi-locus imprinting disturbances (MLID). MLID has been associated with maternal-effect variants that alter the maintenance of methylation at germline-derived differentially methylated regions (gDMRs) in early embryogenesis. Pedigrees of individuals with MLID also include siblings with healthy phenotype. However, it is unknown if these healthy individuals have MLID themselves or if their methylation patterns differ from those associated with imprinting disorders, and in general, if MLID affects the clinical phenotype.

Methods

We have investigated gDMR methylation by locus-specific and whole-genome analyses in a family with multiple pregnancy losses, a child with Beckwith-Wiedemann syndrome (BWS) and a further child with no clinical diagnosis of imprinting disorder or other pathologies.

Results

We detected MLID with different methylation profiles in the BWS-affected and healthy siblings. Whole-exome sequencing demonstrated the presence of novel loss-of-function variants of NLRP5 in compound heterozygosity in the mother. The methylation profiles of the two siblings were compared with those of other cases with MLID and control groups by principal component analysis and unsupervised hierarchical clustering, but while their patterns were clearly separated from those of controls, we were unable to cluster those associated with specific clinical phenotypes among the MLID cases.

Conclusion

The identification of two novel maternal-effect variants of NLRP5 associated with poly-abortivity and MLID adds further evidence to the role of this gene in the maintenance of genomic imprinting in early embryos. Furthermore, our results demonstrate that within these pedigrees, MLID can also be present in the progeny with healthy phenotype, indicating that some sort of compensation occurs between altered imprinted loci in these individuals. The analysis of larger cohorts of patients with MLID is needed to formulate more accurate epigenotype-phenotype correlations.
Carcinoembryonic antigen-targeted photodynamic therapy in colorectal cancer models
Authors: Elekonawo Fortuné M. K. , Bos Desirée L. , Goldenberg David M. , Boerman Otto C. , Rijpkema Mark
Published: December 2019

Background

In colorectal cancer, survival of patients is drastically reduced when complete resection is hampered by involvement of critical structures. Targeted photodynamic therapy (tPDT) is a local and targeted therapy which could play a role in eradicating residual tumor cells after incomplete resection. Since carcinoembryonic antigen (CEA; CEACAM5) is abundantly overexpressed in colorectal cancer, it is a potential target for tPDT of colorectal cancer.

Methods

To address the potential of CEA-targeted PDT, we compared colorectal cancer cell lines with different CEA-expression levels (SW-48, SW-480, SW-620, SW-1222, WiDr, HT-29, DLD-1, LS174T, and LoVo) under identical experimental conditions. We evaluated the susceptibility to tPDT by varying radiant exposure and concentration of our antibody conjugate (DTPA-hMN-14-IRDye700DX). Finally, we assessed the efficacy of tPDT in vivo in 18 mice (BALB/cAnNRj-Foxn1nu/nu) with subcutaneously xenografted LoVo tumors.

Results

In vitro, the treatment effect of tPDT varied per cell line and was dependent on both radiant exposure and antibody concentration. Under standardized conditions (94.5 J/cm2 and 0.5 μg/μL antibody conjugate concentration), the effect of tPDT was higher in cells with higher CEA availability: SW-1222, LS174T, LoVo, and SW-48 (22.8%, 52.8%, 49.9%, and 51.9% reduction of viable cells, respectively) compared to cells with lower CEA availability. Compared to control groups (light or antibody conjugate only), tumor growth rate was reduced in mice with s.c. LoVo tumors receiving tPDT.

Conclusion

Our findings suggest cells (and tumors) have different levels of susceptibility for tPDT even though they all express CEA. Furthermore, tPDT can effectively reduce tumor growth in vivo.
Functional analysis of the Frzb2 gene in Schistosoma japonicum
Authors: Cheng Guifeng , Li Xiaochun , Qin Fanglin , Xu Rong , Zhang Yuanyuan , Liu Jinming , Gu Shaopeng , Jin Yamei
Published: December 2019

Schistosomiasis is a globally important helminthic disease of humans and animals, and it is the second most common parasitic disease after malaria. Eggs produced by mature females are responsible for the disease’s occurrence and spread. Frzb2, a secreted frizzled-related protein, can inhibit Wnt signalling by competitive binding to the specific frizzled protein receptor. In this study, the complete gene sequence of SjFrzb2 was obtained by using 3′-rapid amplification of cDNA ends technology. SjFrzb2 transcript levels at different stages of S. japonicum maturation were evaluated by quantitative real-time RT-PCR analysis. SjFrzb2 was expressed at all developmental stages examined and exhibited the highest transcription level in 7-day-old worms, then gradually decreased during the growth and developmental stages to reach the lowest level at 18 days post-infection. SjFrzb2 gene expression was higher in female worms than in male worms and was significantly higher in female worms from a single-sex infection than in female worms from a bisexual infection. The functions of SjFrzb2 were explored via a small interfering RNA-based gene silencing approach and the soaking method. The results showed that SjFrzb2 gene knockdown impaired the growth and development of S. japonicum in mice, affecting not only the survival and morphological structure of the worms but also their reproductive ability and the viability of the produced eggs. Collectively, these observations imply that Frzb2 may be a novel target for the development of immuno- and/or small molecule-based therapeutics to control schistosomiasis fecundity and transmission.
Roles of extracellular polymeric substances in uranium immobilization by anaerobic sludge
Authors: Zhang Hai-Ling , Cheng Meng-Xi , Li Shi-Cheng , Huang He-Xiang , Liu Wei-Dong , Lyu Xian-Jin , Chu Jian , Ding Huan-Huan , Zhao Dong , Wang Yong-Peng , Huang Feng-Yu
Published: December 2019

The specific roles of extracellular polymeric substances (EPS) and how factors influenced EPS’s roles during U(VI) immobilization are still unclear. In this study, high content of U with the main form of nanoparticles was detected in EPS, accounting for 10–42% of total U(VI) removal. EPS might be utilized as energy source or even as electron donors when external carbon source was unavailable. The influencing degree of each experimental parameter to uranium (U) removal process was elucidated. The influential priority to U(IV)/U(VI) ratios in sludge was as follows: acetate, U(VI), and nitrate. The influential priority to total EPS contents was as follows: U(VI), nitrate and acetate. The complex interaction mechanism between U(VI) and EPS in the U immobilization process was proposed, which might involve three ways including biosorption, bioreduction and bioprecipitation. These results indicate important and various roles of EPS in U(VI) immobilization.
Product of composition and differentiation operators and closures of weighted Bergman spaces in Bloch type spaces
Authors: Zhang Li-Xu
Published: December 2019

Closures of weighted Bergman spaces in Bloch type spaces are investigated in the paper. Moreover, the boundedness and compactness of the product of composition and differentiation operators from Bloch type spaces to closures of weighted Bergman spaces spaces in Bloch type spaces are characterized.
Downregulation of miR-542-3p promotes osteogenic transition of vascular smooth muscle cells in the aging rat by targeting BMP7
Authors: Liu Huan , Wang Hongwei , Yang Sijin , Qian Dehui
Published: December 2019

Background

Aging is believed to have a close association with cardiovascular diseases, resulting in various pathological alterations in blood vessels, including vascular cell phenotypic shifts. In aging vessels, the microRNA(miRNA)-mediated mechanism regulating the vascular smooth muscle cell (VSMC) phenotype remains unclarified. MiRNA microarray was used to compare the expressions of miRNAs in VSMCs from old rats (oVSMCs) and young rats (yVSMCs). Quantitative reverse transcription real-time PCR (qRT-PCR) and small RNA transfection were used to explore the miR-542-3p expression in oVSMCs and yVSMCs in vitro. Calcification induction of yVSMCs was conducted by the treatment of β-glycerophosphate (β-GP). Alizarin red staining was used to detect calcium deposition. Western blot and qRT-PCR were used to investigate the expression of the smooth muscle markers, smooth muscle 22α (SM22α) and calponin, and the osteogenic markers, osteopontin (OPN), and runt-related transcription factor 2 (Runx2). Lentivirus was used to overexpress miR-542-3p and bone morphogenetic protein 7 (BMP7) in yVMSCs. Luciferase reporter assay was conducted to identify the target of miR-542-3p.

Results

Compared with yVSMCs, 28 downregulated and 34 upregulated miRNAs were identified in oVSMCs. It was confirmed by qRT-PCR that oVSMC expressed four times lower miR-542-3p than yVSMCs. Overexpressing miR-542-3p in yVSMCs suppressed the osteogenic differentiation induced by β-GP. Moreover, miR-542-3p targets BMP7 and overexpressing BMP7 in miR-542-3p–expressing yVSMCs reverses miR-542-3p’s inhibition of osteogenic differentiation.

Conclusions

miR-542-3p regulates osteogenic differentiation of VSMCs through targeting BMP7, suggesting that the downregulation of miR-542-3p in oVSMCs plays a crucial role in osteogenic transition in the aging rat.
Gender-specific cephalometric features related to obesity in sleep apnea patients: trilogy of soft palate-mandible-hyoid bone
Authors: Cho Seok Hyun , Jeon Jae-Yun , Jang Kun-Soo , Kim Sang Yoon , Kim Kyung Rae , Ryu Seungho , Hwang Kyung-Gyun
Published: December 2019

Background

The aim of this study is to investigate the relationship between gender-specific and obesity-related airway anatomy in patients with obstructive sleep apnea (OSA) by using cephalometric analyses.

Methods

We retrospectively evaluated 206 patients with suspected OSA undergoing polysomnography and anthropometric measurements such as body mass index, neck circumference, and waist-hip ratio. We checked lateral cephalometry to measure tissue landmarks including angle from A point to nasion to B point (ANB), soft palate length (SPL), soft palate thickness (SPT), retropalatal space (RPS), retrolingual space (RLS), and mandibular plane to hyoid (MPH).

Results

Male with OSA showed significantly increased SPL (P = .006) compared with controls. SPL and MPH had significant correlation with apnea-hypopnea index (AHI) and central obesity. Female with OSA showed significantly increased ANB (P = .013) and SPT (P = .004) compared with controls. The receiver operating characteristic curves revealed that SPT in male and ANB and SPT in female were significant in model 1 (AHI ≥ 5) and model 2 (AHI ≥ 15). MPH was also significant for male in model 2.

Conclusion

Male and female with OSA had distinct anatomic features of the upper airway and different interactions among soft palate, mandible, and hyoid bone.
Multimeasurement aliased-noise attenuation for sparse land seismic acquisition using compressed sensing
Authors: Allouche Nihed , Øzdemir Kemal , Özbek Ali , Hopperstad Jon-Fredrik
Published: December 2019

Land data are contaminated by energetic surface waves that have low apparent velocities relative to the seismic signal. The conventional land acquisition approach to noise attenuation is to deploy arrays of hard-wired geophones whose combined response acts as a spatial filter. Besides the shortcomings of a fixed array response that is sensitive to perturbations, using a large amount of equipment limits the field efficiency of array-based acquisition. The advent of point-receiver acquisition technology addresses some of these limitations by enabling measurement of each single geophone along a receiver line and removing the slowest energetic noise by velocity-based filtering. However, according to the classic sampling theorem, the proper sampling of noise requires sampling the shortest wavelength twice. Because surface waves have slow propagation velocities, it is not feasible to sample the noise properly and a compromise is made between quality and efficiency. We have developed two different methods to improve the efficiency of point-receiver technology by allowing for wider receiver spacing without compromising the coherent noise attenuation capabilities. First, we combine compressed sensing-based methods such as the matching pursuit approach with the gradient measurement inferred from a novel 5C sensor to dealias and attenuate source-generated noise. Second, we have developed a method to design optimized acquisition geometries by using the spectral characteristics of the surface waves, where the objective is to place a limited number of receivers at the most favorable locations to help attenuate the coherent noise. We determine the effectiveness of our methods through synthetic and field data examples in which we find that spatially aliased coherent noise can be reconstructed to a denser grid and attenuated.
Effect of variations in microstructure on clay elastic anisotropy
Authors: Sayers Colin M. , den Boer Lennert D.
Published: December 2019

Rock physics provides a crucial link between seismic and reservoir properties, but it requires knowledge of the elastic properties of rock components. Whereas the elastic properties of most rock components are known, the anisotropic elastic properties of clay are not. Scanning electron microscopy studies of clay in shales indicate that individual clay platelets vary in orientation but are aligned locally. We present a simple model of the elastic properties of a region (domain) of locally aligned clay platelets that accounts for the volume fraction, aspect ratio, and elastic-stiffness tensor of clay platelets, as well as the effective elastic properties of the interplatelet medium. Variations in clay anisotropy are quantified by examining the effects of varying model parameters upon the effective transverse-isotropic (TI) elastic-stiffness tensor of a domain. Statistics of these distributions and correlations between stiffnesses and anisotropy parameters enable the most probable sets of stiffnesses to be identified for rock physics calculations. The mean of these distributions is on the order of twice the mode for in-plane stiffnesses ([Formula: see text], [Formula: see text], [Formula: see text]), but it is of the same order as the mode for out-of-plane stiffnesses ([Formula: see text], [Formula: see text], [Formula: see text]). Despite random sampling, well-defined relations emerge, consistent with similar shale relations reported in the literature. Expressing these relations in terms of [Formula: see text] for a single domain of aligned clay platelets facilitates their general application. In the limit that the volume fraction approaches unity, the elastic stiffnesses thus derived reproduce those of the clay mineral assumed as platelets. Given the elastic-stiffness tensor of a single domain of aligned clay platelets, the effective TI elastic-stiffness tensor of clay is obtained by integrating over the clay-platelet orientation-distribution function.