bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundThe 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).MethodsThe 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.ResultsThe 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.ConclusionPioglitazone 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

Abstract
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

AbstractBackgroundHIV-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.MethodsTo 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.ResultsTGFβ-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.ConclusionsConsistent 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractGene 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

AbstractBackgroundTime-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.MethodsThis 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.ResultsThere 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.ConclusionsIn 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 registrationClinicalTrials.gov:NCT03102216.