bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Postoperative Intensive Care Unit Care Necessary following Cranial Vault Remodeling for Sagittal Synostosis?
Authors: Wolfswinkel Erik M. , Howell Lori K. , Fahradyan Artur , Azadgoli Beina , McComb J. Gordon , Urata Mark M. 
Published: November 2017

Background:
Of U.S. craniofacial and neurosurgeons, 94 percent routinely admit patients to the intensive care unit following cranial vault remodeling for correction of sagittal synostosis. This study aims to examine the outcomes and cost of direct ward admission following primary cranial vault remodeling for sagittal synostosis.

Methods:
An institutional review board–approved retrospective review was undertaken of the records of all patients who underwent primary cranial vault remodeling for isolated sagittal craniosynostosis from 2009 to 2015 at a single pediatric hospital. Patient demographics, perioperative course, and outcomes were recorded.

Results:
One hundred ten patients met inclusion criteria with absence of other major medical problems. Average age at operation was 6.7 months, with a mean follow-up of 19.8 months. Ninety-eight patients (89 percent) were admitted to a general ward for postoperative care, whereas the remaining 12 (11 percent) were admitted to the intensive care unit for preoperative or perioperative concerns. Among ward-admitted patients, there were four (3.6 percent) minor complications; however, there were no major adverse events, with none necessitating intensive care unit transfers from the ward and no mortalities. Average hospital stay was 3.7 days. The institution’s financial difference in cost of intensive care unit stay versus ward bed was $5520 on average per bed per day. Omitting just one intensive care unit postoperative day stay for this patient cohort would reduce projected health care costs by a total of $540,960 for the study period.

Conclusion:
Despite the common practice of postoperative admission to the intensive care unit following cranial vault remodeling for sagittal craniosynostosis, the authors suggest that postoperative care be considered on an individual basis, with only a small percentage requiring a higher level of care.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Prospective Controlled Study of Chin Augmentation by Means of Fat Grafting
Authors: Basile Filipe V. , Basile Antonio R. 
Published: November 2017

Background:
Although fat grafting is a valuable tool for different areas of plastic surgery, its use in the chin area has never been evaluated. A variety of methods are available for adjusting suboptimal chin morphology, and they each present drawbacks.

Methods:
A prospective controlled study was performed to evaluate whether fat grafting increases the chin volume and sagittal projection and to determine the magnitude and nature of the observed changes. Forty-two consecutive patients underwent chin augmentation by means of fat grafting between October of 2014 and January of 2016. All patient images were analyzed using a software program (Fiji package of ImageJ), which creates a three-dimensional version of the chin that is used to produce reliable estimates of the volume and gain in sagittal projection.

Results:
All 42 patients showed an increase in the sagittal projection and total volume at 4 weeks and 6 months after surgery. The sagittal projection increased from 4 mm to 12 mm (average, 8.9 mm) and from 3 mm to 11 mm (average, 7 mm) after 4 weeks and 6 months, respectively. The total volume increase ranged from 3 to 11 ml (average, 8 ml) after 4 weeks and from 3 to 8 ml (average, 7.4 ml) after 6 months.

Conclusion:
Fat grafting to the chin area is a reliable method for improving chin volumes (to a maximum of approximately 10 cc in our study) and sagittal projections (to a maximum of approximately 11 mm in our study).

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Correlates of Linkage to HIV Preexposure Prophylaxis Among HIV-Testing Clients
Authors: Flash Charlene A. , Adegboyega Oluwatobi O. , Yu Xiaoying , Avalos Carmen , Johnson Syundai , Mayer Kenneth H. , Giordano Thomas P. 
Published: November 2017

Background:
Publicly funded HIV-testing sites can identify HIV preexposure prophylaxis (PrEP) candidates and provide PrEP linkage.

Setting:
Harris Health System's HIV clinic, HIV-testing program, and HIV-prevention program (HPP) in Houston, TX, a high HIV-incidence city.

Methods:
A prospective assessment of individuals aged 18 years and older recruited from walk-in HIV testing from December 2013 to April 2015 included risk assessment, HIV testing, and self-administered survey, with follow-up surveys at 6 and 12 months and medical record review.

Results:
The mean age of our sample (n = 300) was 38.3 ± 11.7 years. Men constituted 63.1% of the sample and 53.7% were black non-Hispanic, 26.3% Hispanic, and 14.7% white non-Hispanic. Most were uninsured (63.5%). Only 27% always used condoms, although 67% perceived personal HIV risk. Of 300 participants, 64 (21.3%) linked to PrEP care and 49 (16.3%) took PrEP. In multivariable analysis, compared with heterosexual men, women [adjusted OR (aOR) 4.1, 95% CI: 1.5 to 11.1] and MSM (aOR 10.2, 95% CI: 3.4 to 31.0) were more likely to attend HPP and to take PrEP (aOR 3.0, 95% CI: 1.6 to 15.1 and 3.0, 95% CI: 1.1 to 8.3, respectively). Serodiscordance and PrEP interest correlated with program attendance (aOR 14.0, 95% CI: 6.1 to 32.3 and aOR 6.7, 95% CI: 1.8 to 25.4) and taking PrEP (aOR 13.1, 95% CI: 5.2 to 32.8 and 14.4, 95% CI: 1.8 to 166.9), respectively.

Conclusions:
Preexposure prophylaxis interest, being female or MSM, and serodiscordance correlated with PrEP linkage. Safety-net health systems can facilitate PrEP access in marginalized populations, but the PrEP initiation rates remain low.
Influence of Injection Drug Use–Related HIV Acquisition on CD4 Response to First Antiretroviral Therapy Regimen Among Virally Suppressed Individuals
Authors: Calkins Keri L. , Lesko Catherine R. , Chander Geetanjali , Moore Richard D. , Lau Bryan 
Published: November 2017

Background:
The inflammatory effects of injection drug use (IDU) may result in an impaired immune response to antiretroviral therapy (ART). We examined CD4 response to first ART regimen among individuals in routine HIV care, stratified by IDU-related HIV acquisition.

Setting:
Cohort study including patients who initiated ART between 2000 and 2015 in the Johns Hopkins HIV Clinic.

Methods:
We followed individuals from ART initiation until death, loss to follow-up, loss of viral load suppression (<500 copies/mL), or administrative censoring. We described CD4 trajectories after ART initiation using inverse probability weighted quantile regression models with restricted cubic splines for time. Weights accounted for differences in baseline characteristics of persons comparing those with IDU-related HIV acquisition to those with other HIV acquisition risks (non-IDU) and possible nondifferential censoring due to death, loss to follow-up, or loss of viral load suppression. We also examined CD4 response by strata of CD4 at ART initiation (≤200, 201–350, >350).

Results:
Of 1244 patients initiating ART, 30.4% were IDU. Absolute CD4 cell difference at the 50th percentile comparing IDU with non-IDU was −25 cells [95% confidence interval (CI): −63 to 35], −66 cells (95% CI: −141 to 16), and −91 cells (95% CI: −190 to −5) at 2, 4, and 6 years after ART initiation, respectively. Results were similar (non-IDU with slightly higher CD4 count, but not statistically significant differences) at other percentiles and stratified by baseline CD4.

Conclusions:
CD4 recovery after ART initiation was similar for IDU and non-IDU, conditional on consistent viral load suppression.
Debriefing to Improve Student Ability to Assess and Plan for the Care of Persons With Disability
Authors: Takeda Mikiko Y. , Smith Mark J. , Cone Catherine J. 
Published: November 2017

Introduction
Although recent literature suggests that students should be trained in the care of persons with disability (PWDs) as a form of cultural sensitivity (CS), healthcare professionals may receive limited experience during their formal training. After pharmacy students in 2 previous years of testing failed to adequately assess and plan for the care of a standardized patient’s chief complaint and disability in an Objective Structured Clinical Examination (OSCE), the investigators added debriefing to the OSCE to determine if it would improve student’s ability to assess and plan for the care of PWD.

Methods
Two sequentially enrolled second-year pharmacy school student cohorts participated in this study (control n = 90; intervention n = 82). During the OSCE, students interviewed and examined a standardized patient with a simulated physical disability and other chronic disease states. Students were then instructed to develop a care plan considering the patient’s disability and other disease states. The intervention cohort received debriefing; the control did not. Students documented the care plan in a subjective, objective, assessment, and plan (SOAP) note. Investigators assessed SOAP note score (general ability of students to write a SOAP note) and CS score (specific ability to care for PWD) to determine the effectiveness of the debriefing.

Results
The intervention group showed a significantly higher percent mean CS score than the control group (93.6% ± 19% and 61.1% ± 30.7%, respectively, P < 0.001), translating to a mean of 56.2/60 points earned for the intervention group and 36.7/60 points earned for the control group. Scores ranged from 0 to 60 points for both intervention and control groups. Students in the intervention group had an absolute improvement in pass rates (those students scoring ≥70% on the OSCE) of 59.4% with 92.7% of the students passing in the intervention group versus 33.3% of the students passing in the control group (P < 0.001). The overall SOAP note scores were no different between the 2 cohorts (P = 0.353).

Conclusions
Debriefing added to an OSCE improved students’ performance in developing care plans for disabled patients. Ideally, longitudinal studies should be completed to determine if these skills transfer from debriefings to clinical practice. Development of effective training and assessment methods is essential for students to obtain adequate skills and knowledge to care for persons with disabilities.
Successful Desensitization of T cell Flow Cytometry Crossmatch Positive Renal Transplant Recipients Using Plasmapheresis and Super High-Dose Intravenous Immunoglobulin
Authors: Kakuta Yoichi , Satoh Shigeru , Watarai Yoshihiko , Aikawa Atsushi , Tanabe Kazunari , Harada Hiroshi , Yagisawa Takashi , Ishida Hideki , Okumi Masayoshi , Takahara Shiro 
Published: November 2017

Background
High-dose IVIG (2 g/kg) alone or low-dose IVIG (100 mg/kg) in conjunction with plasma exchange is typically administered as a renal transplantation desensitization therapy. Herein, we monitored changes in T cell and B cell flow cytometry crossmatch (FCXM) to assess the effects of short-term super high-dose IVIG (4 g/kg) administration with plasmapheresis before living-donor renal transplantation.

Methods
Seventeen patients, each showing positive T cell FCXM (median ratio, ≥ 1.4) after 2 rounds of double-filtration plasmapheresis, received 4-day regimens of IVIG (1 g/kg per day) over 1-week periods. T cell and B cell FCXM determinations were obtained after every IVIG dose and again up to 4 weeks after initiating IVIG to ascertain negative conversion of T cell FCXM (median ratio < 1.4). The primary study endpoint was the percentage of patients achieving T cell FCXM-negative status after the 4-dose IVIG regimen.

Results
Upon completion (4 g/kg total) or discontinuation of IVIG administration, 8 (47.1%) of 17 patients displayed negative T cell FCXM. Based on Kaplan-Meier estimates, the cumulative T cell FCXM-negative conversion rate 4 weeks after IVIG administration initiation was 60.3%. The T cell FCXM-negative conversion rates after cumulative doses of 1, 2, 3, and 4 g/kg IVIG were 29.4%, 35.3%, 56.3%, and 46.7%, respectively.

Conclusions
Desensitization of donor-specific antibody-positive renal transplant recipients seems achievable in only a subset of recipients through IVIG dosing (1 g/kg × 4) within 1 week after double-filtration plasmapheresis. The T cell FCXM-negative conversion rate resulting from a cumulative IVIG dose of 3 g/kg or greater surpassed that attained via conventional single-dose IVIG (2 g/kg) protocol. This short-term high-dose IVIG desensitization protocol may be an alternative to conventional protocols for recipients with donor-specific antibody.
Retinal Ganglion Cell Topography in Patients With Visual Pathway Pathology
Authors: Zehnder Simon , Wildberger Hannes , Hanson James V. M. , Lukas Sebastian , Pelz Stefan , Landau Klara , Wichmann Werner , Gerth-Kahlert Christina 
Published: November 2017

Background:
To investigate and quantify the impact of intracranial lesions at different locations within the visual pathway on the ganglion cell layer–inner plexiform layer (GCL–IPL) complex and the retinal nerve fiber layer (RNFL).

Methods:
Patients with intracranial lesions affecting the optic chiasm (Group I) or the optic tract and/or lateral geniculate nucleus (Group II) were included. All patients received kinetic visual field assessment and underwent spectral domain optical coherence tomography. Peripapillary and papillomacular bundle (PMB) RNFL and macular GCL–IPL thickness in 4 perifoveal areas were measured and compared with normal values derived from 52 age-matched healthy control subjects. Z-scores for each parameter of every patient were calculated and compared with the normative data. Z-scores less than −2.0 (e.g., −2.5) were considered as being statistically significant.

Results:
Twenty-two patients (Group I and II: 13 and 9, respectively) were included. Ten of 13 patients in Group I showed significant binasal GCL–IPL thinning, with associated temporal sector thinning in 8 patients. In Group II, all 9 patients showed significant reduction of the GCL–IPL corresponding to the homonymous visual field defect, but only 4 demonstrated RNFL thinning. Contralateral RNFL thinning within the PMB clinically similar to bow-tie atrophy was evident in all patients in Group II. GCL–IPL and RNFL thinning varied in severity from mild (isolated PMB RNFL thickness reduction) to severe (bilateral asymmetrical reduction of PMB RNFL associated with asymmetric, predominantly nasal reduction of GCL–IPL) in Group I.

Conclusion:
Clinical abnormalities in patients with visual pathway lesions are more likely to demonstrate abnormalities of GCL–IPL than global peripapillary RNFL thickness. However, PMB thickness measurement appears to be a valuable tool to detect abnormalities of the anterior visual pathways. If peripapillary RNFL measurements are performed in such patients, PMB thickness should be considered the most useful quantitative parameter.
Instructive starPEG-Heparin biohybrid 3D cultures for modeling human neural stem cell plasticity, neurogenesis, and neurodegeneration
Authors: Papadimitriou Christos , Cosacak Mehmet I. , Mashkaryan Violeta , Celikkaya Hilal , Bray Laura , Bhattarai Prabesh , Hollak Heike , Chen Xin , He Shuijin , Antos Christopher L. , Thomas Alvin K. , Friedrichs Jens , Dahl Andreas , Zhang Yixin , Freudenberg Uwe , Werner Carsten , Kizil Caghan 
Published: November 2017

AbstractThree-dimensional models of human neural development and neurodegeneration are crucial when exploring stem-cell-based regenerative therapies in a tissue-mimetic manner. However, existing 3D culture systems are not sufficient to model the inherent plasticity of NSCs due to their ill-defined composition and lack of controllability of the physical properties. Adapting a glycosaminoglycan-based, cell-responsive hydrogel platform, we stimulated primary and induced human neural stem cells (NSCs) to manifest neurogenic plasticity and form extensive neuronal networks in vitro. The 3D cultures exhibited neurotransmitter responsiveness, electrophysiological activity, and tissue-specific extracellular matrix (ECM) deposition. By whole transcriptome sequencing, we identified that 3D cultures express mature neuronal markers, and reflect the in vivo make-up of mature cortical neurons compared to 2D cultures. Thus, our data suggest that our established 3D hydrogel culture supports the tissue-mimetic maturation of human neurons. We also exemplarily modeled neurodegenerative conditions by treating the cultures with Aβ42 peptide and observed the known human pathological effects of Alzheimer’s disease including reduced NSC proliferation, impaired neuronal network formation, synaptic loss and failure in ECM deposition as well as elevated Tau hyperphosphorylation and formation of neurofibrillary tangles. We determined the changes in transcriptomes of primary and induced NSC-derived neurons after Aβ42, providing a useful resource for further studies. Thus, our hydrogel-based human cortical 3D cell culture is a powerful platform for studying various aspects of neural development and neurodegeneration, as exemplified for Aβ42 toxicity and neurogenic stem cell plasticity.SignificanceNeural stem cells (NSC) are reservoir for new neurons in human brains, yet they fail to form neurons after neurodegeneration. Therefore, understanding the potential use of NSCs for stem cell-based regenerative therapies requires tissue-mimetic humanized experimental systems. We report the adaptation of a 3D bio-instructive hydrogel culture system where human NSCs form neurons that later form networks in a controlled microenvironment. We also modeled neurodegenerative toxicity by using Amyloid-beta4 peptide, a hallmark of Alzheimer’s disease, observed phenotypes reminiscent of human brains, and determined the global gene expression changes during development and degeneration of neurons. Thus, our reductionist humanized culture model will be an important tool to address NSC plasticity, neurogenicity, and network formation in health and disease.
Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPS cells
Authors: Fu Kai , Chronis Constantinos , Soufi Abdenour , Bonora Giancarlo , Edwards Miguel , Smale Steve , Zaret Kenneth S. , Plath Kathrin , Pellegrini Matteo 
Published: November 2017

AbstractBoth human and mouse fibroblasts can be reprogrammed to pluripotency with Oct4, Sox2, Klf4, and c-Myc (OSKM) transcription factors. While both systems generate pluripotency, human reprogramming takes considerably longer than mouse. To assess additional similarities and differences, we sought to compare the binding of the reprogramming factors between the two systems. In human fibroblasts, the OSK factors initially target many more closed chromatin sites compared to mouse. Despite this difference, the intra- and intergenic distribution of target sites, target genes, primary binding motifs, and combinatorial binding patterns between the reprogramming factors are largely shared. However, while many OSKM binding events in early mouse cell reprogramming occur in syntenic regions, only a limited number is conserved in human. In summary, these findings suggest similar general effects of OSKM binding across these two species, even though the detailed regulatory networks have diverged significantly.
Deferiprone, an Iron Chelator, is Preventive and Therapeutic in Experimental Crescentic Glomerulonephritis
Authors: Chen Tai-Di , Ko Jeong-Hun , Prendecki Maria , McAdoo Stephen P. , Pusey Charles D. , Terence Cook H. , Behmoaras Jacques 
Published: November 2017

AbstractCrescentic glomerulonephritis represents the most severe form of antibody-mediated glomerulonephritis. It is an important cause of renal dysfunction worldwide and there is a need for more effective treatment. Deferiprone, an orally active iron chelator, is widely used in patients with thalassemia. Here we present the preventive and therapeutic effects of deferiprone in experimental crescentic glomerulonephritis. Nephrotoxic nephritis was induced in Wistar Kyoto rats, and preventive treatment with deferiprone substantially lowered glomerular crescent formation by 84%, with 70% reduction in proteinuria. In established glomerulonephritis, deferiprone treatment effectively halted glomerular inflammation, reversed progression of proteinuria, and prevented deterioration of renal function. Deferiprone reduced glomerular inflammatory cell proliferationin vivo.It was internalised by monocyte/macrophages and inhibited their proliferationin vitro,without showing cellular toxicity. Interestingly, deferiprone showed a neutralizing effect on superoxide anions, and prevented the expression of monocyte chemoattractant protein-1 and matrix metalloproteinase 9, 12 and 14, by primary macrophages. These results suggest that deferiprone partly exerts its renal protective effect through inhibition of monocyte/macrophage proliferation and function by iron-chelating and anti-oxidant properties, respectively. We conclude that deferiprone is an effective treatment in a severe and reproducible model of antibody-mediated glomerular inflammation that resembles human crescentic glomerulonephritis, indicating its therapeutic potential.
Prioritized memory access explains planning and hippocampal replay
Authors: Mattar Marcelo G. , Daw Nathaniel D. 
Published: November 2017

AbstractTo make decisions, animals must evaluate outcomes of candidate choices by accessing memories of relevant experiences. Yet little is known about which experiences are considered or ignored during deliberation, which ultimately governs choice. Here, we propose a normative theory to predict which memories should be accessed at each moment to optimize future decisions. Using nonlocal “replay” of spatial locations in hippocampus as a window into memory access, we simulate a spatial navigation task where an agent accesses memories of locations sequentially, ordered by utility: how much extra reward would be earned due to the computation enabling better choices. This prioritization balances two desiderata: the need to evaluate imminent choices, vs. the gain from propagating newly encountered information to predecessor states. We show that this theory offers a unifying account of a range of hitherto disconnected findings in the place cell literature such as the balance of forward and reverse replay, biases in the replayed content, and effects of experience. Accordingly, various types of nonlocal events during behavior and rest are re-interpreted as instances of a single choice evaluation operation, unifying seemingly disparate proposed functions of replay including planning, learning and consolidation, and whose dysfunction may underlie pathologies like rumination and craving.