bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cranioplasty length of stay: Relationship with indication, surgical decision-making factors, and sex
Authors: Northam Weston , Chandran Avinash , Adams Crystal , Barczak-Scarboro Nikki E. , Quinsey Carolyn 
Published: December 2019

Objectives Cranioplasty is being performed more often due to rising rates of decompressive craniectomy. Hospital length of stay is a quality metric which has not been directly studied after cranioplasty. This study aims to identify factors associated with length of stay after cranioplasty to better understand their outcomes. Patients and methods A retrospective review was conducted at a single academic center from 2007 to 2015 for all patients >18 years of age who received cranioplasty. Baseline data from 148 patients were recorded including demographics, clinical characteristics, and surgeon decision-making factors for cranioplasty. Post-operative complications within 30 days after cranioplasty were recorded in addition to disposition and discharge data. Weibull accelerated failure time models were used to identify significant associations with length of stay after cranioplasty. Results The overall post-operative complication rate was 27.0%, and the most frequent indication for craniectomy was traumatic brain injury. The majority (72.3%) of patients returned home, compared to other disposition, and median length of stay was 2.0 days (interquartile range = 2.0). Average length of stay was 7.7 days in men, as compared with 2.4 days in women, and even upon adjusting for covariate effects, length of stay was longer in men than in women irrespective of post-operative complications. When time-to-cranioplasty fell between 0 and 30 days, average length of stay was 19.2 days, as compared with 10.3 days when time-to-cranioplasty fell between 30 and 90 days, and 2.5 days when time-to-cranioplasty was >90 days. After adjustment for covariate effects, the association between time-to-cranioplasty and length of stay was maintained only in patients without post-operative complications. Conclusions Length of stay can inform our understanding of outcomes after cranioplasty. In our study, length of stay was associated with sex, indication for craniectomy, and surgical decision-making (time-to-cranioplasty and implant material), but time-to-cranioplasty was only associated in patients without post-operative complications. These relationships should be seen not as direct causation, but rather as tools to add to our understanding of this relatively complicated procedure.
A Novel Video-Based Patient Education Program to Reduce Penile Prosthetic Surgery Cancellations
Authors: Ballon-Landa Eric , Clavijo Raul , Gross Martin , Tapscott Ashley , Ramasamy Ranjith , Bowen Ashley , Freedman Sheldon , Wierschem Michael , Welliver Charles , Simoncini Frank , Duboy Alberto , Simhan Jay , Bullock Arnold , Perito Paul , Hsieh Tung-Chin 
Published: December 2019

Penile prosthetic surgery is an effective treatment for men with erectile dysfunction. Cancellation of surgery is disruptive and costly to patients, physicians, and the healthcare system. This pilot study sought to analyze surgery cancellations and implement a video-based patient education program to decrease surgery noncompletion. Baseline penile prosthetic surgery completion, rescheduling, and cancellation rates among consecutively scheduled surgeries were determined using a national cohort. Selected prosthetic surgeons then implemented Vidscrip, a video-based patient education program. Prerecorded videos were delivered via text message 14 days, 7 days, and 1 day preoperatively, as well as 1 day postoperatively. Subsequent analysis determined noncompletion rates, reasons for noncompletion, surgeon volume, and video utilization. Two-hundred twenty-six surgeries were scheduled in the baseline cohort; 141 were completed, and 85 were rescheduled or canceled. Among the intervention cohort, 290 patients completed, 7 rescheduled, and 37 canceled surgery. After program implementation, the surgery noncompletion rate was reduced compared to baseline (13.2% vs. 37.6%, p < .05), corresponding to a number needed to treat of 4.1. When stratified by surgeon volume, there was no difference in noncompletion rate (>20 cases vs. ≤20 cases: 8.20% vs. 32.0%, p = .35). Video utilization was widely variable among practices (median viewing time 58.6 min, IQR 5.09–113). Penile prosthetic surgery is frequently rescheduled or canceled. Implementing a video-based patient education program reduces surgery noncompletion, improving efficiency and quality of care. Wider implementation is needed to validate these findings, while cost-effectiveness analyses may further support their broad adoption.
The Differential and Combined Action of Insulin Glargine and Lixisenatide on the Fasting and Postprandial Components of Glucose Control
Authors: Gautier Thibault , Umpierrez Guillermo , Renard Eric , Kovatchev Boris 
Published: December 2019

Background: iGlarLixi is an injectable combination of long acting insulin glargine (iGlar) and glucagon-like peptide 1 receptor agonist lixisenatide in a fixed ratio, which was proven safe and effective for the treatment of type 2 diabetes. Lixisenatide and iGlar act differently on fasting and postprandial plasma glucose (fasting plasma glucose [FPG] and postprandial glucose [PPG]). Here, we deconstruct quantitatively their respective FPG and PPG effects. Method: This post hoc study analyzes data from the Lixilan-O trial, where 1170 subjects with type 2 diabetes were randomly assigned to 30 weeks of once daily injections of lixisenatide, iGlar, and iGlarLixi (1:2:2). The FPG and PPG components of glucose control were assessed in terms of mean glucose (fasting mean plasma glucose [FMPG] and prandial mean plasma glucose [PMPG], respectively). The MPGP was computed across all meals as a delta between post- and premeal glucose; glucose variability was measured by the high blood glucose index (HBGI) (fasting HBGI and prandial HBGI [PHBGI], respectively), and glycemic exposure measured by area under the curve (AUC) computed overall. All metrics were derived from seven-point self-monitoring glucose profiles. Results: Insulin glargine lowered significantly FMPG by 15.3 mg/dL ( P < .01) without any significant change in PMPG. Lixisenatide, when added to iGlar, reduced PMPG by 9.7 mg/dL ( P < .01), AUC by 96.3 mg∙h/dL ( P < .01), and PHBGI by 2.4 ( P < .01), primarily due to attenuation of PPG and without significant change in mean FPG. Conclusion: Insulin glargine and lixisenatide act selectively on FPG and PPG. Their combination iGlarLixi offers more effective glucose control than its components due to the cumulative effect on FPG and PPG, which is evidenced by reduced average glycemia, glycemic exposure, and glucose variability.
The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease
Authors: Srinagesh Hrishikesh K. , Özbek Umut , Kapoor Urvi , Ayuk Francis , Aziz Mina , Ben-David Kaitlyn , Choe Hannah K. , DeFilipp Zachariah , Etra Aaron , Grupp Stephan A. , Hartwell Matthew J. , Hexner Elizabeth O. , Hogan William J. , Karol Alexander B. , Kasikis Stelios , Kitko Carrie L. , Kowalyk Steven , Lin Jung-Yi , Major-Monfried Hannah , Mielke Stephan , Merli Pietro , Morales George , Ordemann Rainer , Pulsipher Michael A. , Qayed Muna , Reddy Pavan , Reshef Ran , Rösler Wolf , Sandhu Karamjeet S. , Schechter Tal , Shah Jay , Sigel Keith , Weber Daniela , Wölfl Matthias , Wudhikarn Kitsada , Young Rachel , Levine John E. , Ferrara James L. M. 
Published: December 2019

Key Points
The MAGIC algorithm probability, computed from 2 serum biomarkers, predicts mortality in all GVHD grades after 4 weeks of treatment. Dynamic changes in the MAGIC algorithm probability occur within all biomarker risk groups and can guide therapy.
Antiviral activity of mitoxantrone dihydrochloride against human herpes simplex virus mediated by suppression of the viral immediate early genes
Authors: Huang Qiang , Hou Jue , Yang Peng , Yan Jun , Yu Xiaoliang , Zhuo Ying , He Sudan , Xu Feng 
Published: December 2019

Abstract
Background
HSV-1 is a common pathogen that infects 50–90% of the human population worldwide. HSV-1 causes numerous infection-related diseases, some of which are severely life-threatening. There are antiviral medications with activity against HSV-1. However, with the emergence of drug-resistant mutant strains of HSV-1, there is an urgent need to develop new effective anti-HSV-1 agents.

Methods
Therefore, we screened a chemical library of approximately 1500 compounds to identify inhibitors of HSV-1-induced toxicity for further drug development. Moreover, we performed several experiments, including western blot analysis, Q-PCR analysis and luciferase activity assay, to explore the antiviral mechanism of the candidates.

Results
Here, we identified a small molecule, mitoxantrone dihydrochloride, with potency against HSV-1-induced toxicity. Furthermore, the viral titers and expression levels of HSV-1 viral proteins were potently reduced by the presence of MD in many cell lines. Using Q-PCR analysis, we found that MD efficiently reduced the transcription of viral genes that are essential for DNA synthesis, namely, UL5, UL9, UL29, UL30, UL42 and UL52. Notably, MD also significantly inhibited the transcription of the immediate early genes ICP0, ICP22, ICP27 and ICP47, all of which are required for the expression of early and late viral gene products. Using immunofluorescence and western blot analysis, we found that the antiviral effect of MD was independent of the activation of the NF-κB and MAPK pathways. Furthermore, we found that the reduction in the transcription of viral immediate early genes was not related to the promoter activities of ICP0.

Conclusions
Therefore, the identification of compound MD as an inhibitor of toxicity induced by HSV-1 highlights its potential use in the development of novel anti-HSV-1 drugs.
A case report of two siblings with Alstrom syndrome without hearing loss associated with two new ALMS1 variants
Authors: Shurygina Maria F. , Parker Maria A. , Schlechter Catie L. , Chen Rui , Li Yumei , Weleber Richard G. , Yang Paul , Pennesi Mark E. 
Published: December 2019

Abstract
Background
Alström syndrome (AS) is a rare monogenic disorder characterized by progressive multi-organ pathology including retinal degeneration, hearing impairment and type 2 diabetes. Here we present clinical features in two siblings diagnosed with Alström syndrome associated with two novel changes in ALMS1.

Case presentation
Two siblings originally diagnosed as having achromatopsia presented with mild light sensitivity, nonspecific otitis media, and mild developmental delay during the first decade of life with a relatively stable ocular appearance during second decade, late onset of nystagmus and dyschromatopsia (after 20 years) and preserved vision during the third decade of life. One sibling had late onset hearing loss and both siblings had symmetric high myopia, normal stature, and ptosis. Clinical findings revealed structural and functional tests consistent with a cone-rod dystrophy. Novel variants c.9894dupC (p.S3298 fs) and c.10769delC (p.T3590 fs) in ALMS1 gene were found.

Conclusions
Two North American siblings who presented with a mild clinical phenotype of Alström syndrome were found to have novel mutations in ALMS1. These two frame-shift mutations segregated with the disease phenotype lending evidence to their pathogenicity.
The maternal antibody against diphtheria, tetanus and pertussis showed distinct regional difference in China
Authors: Meng Qinghong , Qian Qinghui , Li Li , Liu Dandan , Gao Wei , Yuan Lin , Yao Kaihu 
Published: December 2019

Abstract
Background
Passive transferred antibodies to the fetus play an essential role on protecting neonates and young infants until infant vaccination is more efficacious. However, very little is known about the discrepancy of DTP vaccine associated antibodies level in neonates from different economic areas in China.

Methods
In 2018, 200 neonates hospitalized in Shunyi Women and Children’s Hospital in Beijing, and 238 neonates hospitalized in Qianjiang Central Hospital located in the southwestern mountainous areas were included in this study. Antibodies specific for the antigens covered by DTP vaccine were determined using ELISA Kits (Euroimmun, Lübeck, Germany). The cut off value of ≥0.1 IU/ml (anti-diphtheria, anti-Dtx), > 0.1 IU/ml (anti-tetanus, anti-Ttx) and > 40 IU/ml (anti-pertussis toxin, anti-Ptx) were used to assess the percentage of protected neonates, respectively.

Results
The antibody levels in the neonates from Qianjiang (0.04 IU/ml for anti-Dtx IgG and 0.07 IU/ml for anti-Ttx IgG) were significantly lower than those from Shunyi (0.12 IU/ml for anti-Dtx IgG and 0.18 IU/ml for anti-Ttx IgG). The prevalence of protective anti-Dtx and anti-Ttx IgG were lower in the neonates from Qianjiang (7.1% for anti-Dtx IgG and 7.6% for anti-Ttx IgG) than in those from Shunyi (30.5% for anti-Dtx and 38.5% for anti-Ttx). The neonates from Qianjiang also had lower detectable rate of anti-Dtx (57.5%) and anti-Ttx IgG (55.8%) than neonates from Shunyi (97.5% for anti-Dtx and 71.0% for anti-Ttx). However, the detectable rate of anti-Ptx IgG in neonates from Qianjiang (39.9%) was higher significantly than in those from Shunyi (30.5%). Two neonates from Qianjiang have anti-PT IgG ≥100.0 IU/ml, which suggested that their mothers have a recent pertussis course.

Conclusions
The regional discrepancy of the protective antibody rates might be caused by different vaccine coverage and pertussis exposure, which suggested the importance of Tdap booster immunization for pregnant women or women at childbearing age, those living undeveloped areas in particular.
The incidence of bone marrow oedema at the sacroiliac joints in a non-rheumatological population — a retrospective cohort study
Authors: Nygaard A. , Jurik A. G. , Lund C. , Schiøttz-Christensen B. 
Published: December 2019

Abstract
Background
The purpose of this study is to determine the incidence of bone marrow oedema (BME) at magnetic resonance imaging (MRI) of the sacroiliac joints (SIJ) in a non- rheumatological population, and to explore whether patient-reported outcome measures are suitable for predicting BME at the SIJ at referral. Furthermore, to investigate the final clinical diagnoses three months after initial SIJ MRI.

Methods
This study was a retrospective cohort study consisting of patients 18–45 years of age that were referred for a SIJ MRI between 1 July 2016 to 30 June 2017 at the Department of Radiology in Lillebaelt Hospital, Denmark. The SIJ MRI radiological reports were evaluated for signs of BME. Principal and secondary diagnoses according to the 10th version of International Classification of Diseases (ICD-10)—three months after the initial MRI—were identified in the electronic patient record system. For a subgroup of patients, patient- reported outcome measures, such as the 23-item Roland Morris Disability Questionnaire, quality of life and pain intensity in the back and leg were included from the local SpineData database.

Results
In total, 333 patients were included, and 187 (56.2%) of those patients received a final diagnosis within three months after the SIJ MRI. BME was detected in 63 (18.9%) patients; 17 (9.1%) patients had both BME at SIJ MRI and were diagnosed with spondyloarthritis (M45/M46). There was no statistically significant difference between patients with and without BME regarding demographics, quality of life, pain descriptions or function.

Conclusions
The incidence of BME in the cohort correlates well to previous studies regarding the incidence of SIJ MRI changes in non-rheumatological populations in Denmark. Patient-reported outcome measures do not seem to contribute to identifying patients with early-phase BME in a non-rheumatological population.
iRGD-guided tamoxifen polymersomes inhibit estrogen receptor transcriptional activity and decrease the number of breast cancer cells with self-renewing capacity
Authors: Diaz Bessone María Inés , Simón-Gracia Lorena , Scodeller Pablo , Ramirez María de los Angeles , Lago Huvelle María Amparo , Soler-Illia Galo J. A. A. , Simian Marina 
Published: December 2019

Abstract
Background
Tamoxifen (Tam) is the most frequent treatment for estrogen receptor (ER) positive breast cancer. We recently showed that fibronectin (FN) leads to Tam resistance and selection of breast cancer stem cells. With the aim of developing a nanoformulation that would simultaneously tackle ER and FN/β1 integrin interactions, we designed polyethylene glycol-polycaprolactone polymersomes polymersomes (PS) that carry Tam and are functionalized with the tumor-penetrating iRGD peptide (iRGD-PS-Tam).

Results
Polyethylene glycol-polycaprolactone PS were assembled and loaded with Tam using the hydration film method. The loading of encapsulated Tam, measured by UPLC, was 2.4 ± 0.5 mol Tam/mol polymer. Physicochemical characterization of the PS demonstrated that iRGD functionalization had no effect on morphology, and a minimal effect on the PS size and polydispersity (176 nm and Pdi 0.37 for iRGD-TAM-PS and 171 nm and Pdi 0.36 for TAM-PS). iRGD-PS-Tam were taken up by ER+ breast carcinoma cells in 2D-culture and exhibited increased penetration of 3D-spheroids. Treatment with iRGD-PS-Tam inhibited proliferation and sensitized cells cultured on FN to Tam. Mechanistically, treatment with iRGD-PS-Tam resulted in inhibition ER transcriptional activity as evaluated by a luciferase reporter assay. iRGD-PS-Tam reduced the number of cells with self-renewing capacity, a characteristic of breast cancer stem cells. In vivo, systemic iRGD-PS-Tam showed selective accumulation at the tumor site.

Conclusions
Our study suggests iRGD-guided delivery of PS-Tam as a potential novel therapeutic strategy for the management of breast tumors that express high levels of FN. Future studies in pre-clinical in vivo models are warranted.
Renal function change after switching tenofovir disoproxil fumarate for tenofovir alafenamide in the HIV-positive patients of a metropolitan sexual health service
Authors: Turner Dane , Drak Douglas , O’Connor Catherine C. , Templeton David J. , Gracey David M. 
Published: December 2019

Abstract
Background
Tenofovir disoproxil fumarate (TDF) is widely used in the management of HIV-infection, but has been associated with renal impairment in a small proportion of patients. Tenofovir alafenamide (TAF), a novel prodrug of tenofovir, causes less renal impairment and can improve renal function in patients switched from TDF. The factors which predict improved renal function in patients switching from TDF to TAF have yet to be described.

Aim
To determine which patient factors are associated with an improvement in renal function following the switch from a TDF- to a TAF-based HIV antiretroviral regimen.

Methods
A retrospective analysis was performed of a cohort from a publicly funded sexual health clinic in Sydney, Australia. All HIV-positive clinic patients switched from a TDF- to TAF-containing regimen between January 2016 and August 2018 were eligible for inclusion. Laboratory results were obtained from patients’ electronic medical records. The statistical significance of differences between pre- and post-switch means was determined by paired t-tests, adjusted for baseline values, and associations between continuous variables by univariate linear regression.

Results
79 patients met inclusion criteria. The majority were male (89%), with a median age of 44 years (IQR: 34.5 to 53). Patients had a mean pre-switch estimated glomerular filtration rate (eGFR) of 95 ± 2 mL/min/1.73 m2, and there was no significant change post-switch (p = 0.062). Pre-switch eGFR was a significant predictor of the magnitude of eGFR change after the switch (p < 0.001), but there was no significant association with age (p = 0.189), cumulative TDF exposure (p = 0.454) or baseline urinary protein to creatinine ratio (p = 0.814).

Conclusion
While there was no significant difference in mean eGFR, in patients switched from TDF to TAF, baseline eGFR was a significant predictor of the change in eGFR. This suggests that patients on TDF with poorer baseline renal function would benefit more from switching to TAF. Further study to explore this association is warranted.
Prophylactic antibiotic bundle compliance and surgical site infections: an artificial neural network analysis
Authors: Walczak Steven , Davila Marbelly , Velanovich Vic 
Published: December 2019

Abstract
Background
Best practice “bundles” have been developed to lower the occurrence rate of surgical site infections (SSI’s). We developed artificial neural network (ANN) models to predict SSI occurrence based on prophylactic antibiotic compliance.

Methods
Using the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) Tampa General Hospital patient dataset for a six-month period, 780 surgical procedures were reviewed for compliance with SSI guidelines for antibiotic type and timing. SSI rates were determined for patients in the compliant and non-compliant groups. ANN training and validation models were developed to include the variables of age, sex, steroid use, bleeding disorders, transfusion, white blood cell count, hematocrit level, platelet count, wound class, ASA class, and surgical antimicrobial prophylaxis (SAP) bundle compliance.

Results
Overall compliance to recommended antibiotic type and timing was 92.0%. Antibiotic bundle compliance had a lower incidence of SSI’s (3.3%) compared to the non-compliant group (8.1%, p = 0.07). ANN models predicted SSI with a 69–90% sensitivity and 50–60% specificity. The model was more sensitive when bundle compliance was not used in the model, but more specific when it was. Preoperative white blood cell (WBC) count had the most influence on the model.

Conclusions
SAP bundle compliance was associated with a lower incidence of SSI’s. In an ANN model, inclusion of the SAP bundle compliance reduced sensitivity, but increased specificity of the prediction model. Preoperative WBC count had the most influence on the model.
DNMT1 recruited by EZH2-mediated silencing of miR-484 contributes to the malignancy of cervical cancer cells through MMP14 and HNF1A
Authors: Hu Yang , Wu Fuxia , Liu Yankun , Zhao Qian , Tang Hua 
Published: December 2019

AbstractBackgroundEmerging evidence indicates that dysregulation of microRNAs (miRNAs) contributes to cervical cancer (CC) tumorigenesis and development. Previous work showed that miR-484 which regulated the EMT process was obviously downregulated in CC. However, little is known about the precise mechanism.ResultsWe found that the deficiency of EZH2-recruited DNA methyltransferases DNMT1 reduced the CpG methylation of miR-484 promoter and then increased the miR-484 expression. Furthermore, the cell membrane-bound matrix metalloproteinase (MMP14) and the hepatocyte nuclear factor 1A (HNF1A) were found to be downregulated by miR-484. miR-484 repressed the expression of MMP14 and HNF1A inhibiting CC growth and metastasis in vitro and in vivo. Upregulation of MMP14 and HNF1A promotes the CC cell adhesion and EMT, all of which contribute to cell motility and metastasis. Moreover, miR-484 negatively regulates the WNT/MAPK and TNF signaling pathway by downregulating HNF1A and MMP14 respectively. Thus, miR-484, who is downregulated by DNMT1-mediated hypermethylation in its promoter, functions as a tumor suppressor by inhibiting MMP14 and HNF1A expression in CC.ConclusionOur finding characterizes miR-484 as a key suppressive regulator in CC metastasis and reveals a DNMT1-mediated epigenetic mechanism for miR-484 silencing, expanding our understanding of the molecular mechanism underlying CC progression and metastasis.Graphical abstract