bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitivity of pituitary gonadotropes to hyperglycemia leads to epigenetic aberrations and reduced follicle‐stimulating hormone levels
Authors: Feldman Alona , Saleh Ayah , Pnueli Lilach , Qiao Sen , Shlomi Tomer , Boehm Ulrich , Melamed Philippa 
Published: August 2018

ABSTRACTThe connection between metabolism and reproductive function is well recognized, and we hypothesized that the pituitary gonadotropes, which produce luteinizing hormone and follicle‐stimulating hormone (FSH), mediate some of the effects directly via insulin‐independent glucose transporters, which allow continued glucose metabolism during hyperglycemia. We found that glucose transporter 1 is the predominant glucose transporter in primary gonadotropes and a gonadotrope precursor–derived cell line, and both are responsive to culture in high glucose; moreover, metabolite levels were altered in the cell line. Several of the affected metabolites are cofactors for chromatin‐modifying enzymes, and in the gonadotrope precursor–derived cell line, we recorded global changes in histone acetylation and methylation, decreased DNA methylation, and increased hydroxymethylation, some of which did not revert to basal levels after cells were returned to normal glucose. Despite this weakening of epigenetic‐mediated repression seen in the model cell line, FSH β‐subunit (Fshb) mRNA levels in primary gonadotropes were significantly reduced, apparently due in part to increased autocrine/paracrine effects of inhibin. However, unlike thioredoxin interacting protein and inhibin subunit α, Fshb mRNA levels did not recover after the return of cells to normal glucose. The effect on Fshb expression was also seen in 2 hyperglycemic mouse models, and levels of circulating FSH, required for follicle growth and development, were reduced. Thus, hyperglycemia seems to target the pituitary gonadotropes directly, and the likely extensive epigenetic changes are sensed acutely by Fshb. This scenario would explain clinical findings in which, even after restoration of optimal blood glucose levels, fertility often remains adversely affected. However, the relative accessibility of the pituitary provides a possible target for treatment, particularly crucial in the young in which hyperglycemia is increasingly common and fertility most relevant.—Feldman, A., Saleh, A., Pnueli, L., Qiao, S., Shlomi, T., Boehm, U., Melamed, P. Sensitivity of pituitary gonadotropes to hyperglycemia leads to epigenetic aberrations and reduced follicle‐stimulating hormone levels. FASEB J. 33, 1020–1032 (2019). www.fasebj.org
Trends in Lumbar Fusion Procedure Rates and Associated Hospital Costs for Degenerative Spinal Diseases in the United States, 2004 to 2015
Authors: Martin Brook I. , Mirza Sohail K. , Spina Nicholas , Spiker William R. , Lawrence Brandon , Brodke Darrel S. 
Published: August 2018

Study Design.
Analysis of National Inpatient Sample (NIS), 2004 to 2015.

Objective.
Describe recent trends in US rates of lumbar fusion procedures and associated costs, by surgical indication.

Summary of Background Data.
Spinal fusion is appropriate for spinal deformity and instability, but evidence of effectiveness is limited for primary disc herniation and spinal stenosis without instability. It remains controversial for treatment of axial pain secondary to degenerative disc disease. There are potential non-instability, non-deformity indications for fusion surgery, including but not limited to severe foraminal stenosis and third-time disc herniation.

Methods.
Elective lumber fusion trends were reported using Poisson regression, grouped by indication as degenerative scoliosis, degenerative spondylolisthesis, spinal stenosis, disc herniation, and disc degeneration. Generalize linear regression was used to estimate trends in hospital costs, adjusted for age, sex, indication, comorbidity, and inflation.

Results.
Volume of elective lumbar fusion increased 62.3% (or 32.1% per 100,000 US adults), from 122,679 cases (60.4 per 100,000) in 2004 to 199,140 (79.8 per 100,000) in 2015. Increases were greatest among age 65 or older, increasing 138.7% by volume (73.2% by rate), from 98.3 per 100,000 (95% confidence interval [CI] 97.2, 99.3) in 2004 to 170.3 (95% CI 169.2, 171.5) in 2015. Although the largest increases were for spondylolisthesis (+47,390 operations, 111%) and scoliosis (+16,129 operations, 186.6%), disc degeneration, herniation, and stenosis combined to accounted for 42.3% of total elective lumbar fusions in 2015. Aggregate hospital costs increased 177% during these 12 years, exceeding $10 billion in 2015, and averaging more than $50,000 per admission.

Conclusion.
While the prevalence of spinal pathologies is not known, the rate of elective lumbar fusion surgery in the United States increased most for spondylolisthesis and scoliosis, indications with relatively good evidence of effectiveness. The proportion of fusions coded for indications with less evidence of effectiveness has slightly decreased in the most recent years.

Level of Evidence: 3
Transcranial Doppler in the Diagnosis of Cerebral Vasospasm: An Updated Meta-Analysis
Authors: Mastantuono Jean-Mathieu , Combescure Christophe , Elia Nadia , Tramèr Martin R. , Lysakowski Christopher 
Published: August 2018

Objectives:
To evaluate the performance of transcranial Doppler and transcranial color-coded duplex Doppler in patients with cerebral vasospasm due to aneurysm rupture. Angiography was considered as the gold standard comparator.

Data Sources:
Search in MEDLINE, Embase, and Central from January 2001 to October 2017, without language restriction. Bibliographies of retrieved articles were screened for additional studies.

Study Selection:
Randomized studies comparing transcranial Doppler or transcranial color-coded duplex Doppler with angiography in adults.

Data Extraction:
Data were extracted independently by several investigators. Sensitivity and specificity were combined across studies using a bivariate model. Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used for reporting and Quality Assessment of Diagnostic Accuracy Studies-2 for quality assessment.

Data Synthesis:
We included 18 studies. Fifteen tested transcranial Doppler. For the middle cerebral artery (10 studies, 1,408 tests), the pooled sensitivity was 66.7% (95% CI, 55.9–75.9) and specificity was 89.5% (80.3–94.7). Three studies (278 tests) tested transcranial color-coded duplex Doppler for the middle cerebral artery. The pooled sensitivity was 81.5% (66.0–90.0), and specificity was 96.6% (93.0–98.0). For an arbitrarily chosen prevalence of vasospasm of 70%, positive and negative predictive values were 93.7% (88.9–96.6) and 53.4% (46.7–60.9) for transcranial Doppler and 98.2% (96.4–99.1) and 69.1% (56.1–80.9) for transcranial color-coded duplex Doppler.

Conclusions:
Assuming a high prevalence of vasospasm of the middle cerebral artery, both transcranial Doppler and transcranial color-coded duplex Doppler are likely to detect it, but neither is useful to exclude it. There is no convincing evidence that the accuracy of transcranial color-coded duplex Doppler is any better than that of transcranial Doppler. For arteries other than middle cerebral artery, there is a lack of evidence of the usefulness of transcranial Doppler.
Timing of Rotavirus Vaccine Doses and Severe Rotavirus Gastroenteritis Among Vaccinated Infants in Low- and Middle-income Countries
Authors: Gruber Joann F. , Becker-Dreps Sylvia , Hudgens Michael G. , Brookhart M. Alan , Thomas James C. , Jonsson Funk Michele 
Published: August 2018

Background:
Altering rotavirus vaccine schedules may improve vaccine performance in low- and middle-income countries. We analyzed data from clinical trials of the monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in low- and middle-income countries to understand the association between vaccine dose timing and severe rotavirus gastroenteritis incidence.

Methods:
We assessed the association between variations in rotavirus vaccine administration schedules and severe rotavirus gastroenteritis risk. We used the complement of the Kaplan–Meier survival estimator to estimate risk differences for different schedules. To adjust risk differences (RDs) for confounding, we calibrated estimates in the vaccinated arm using estimates from the placebo arm.

Results:
There were 3,114 and 7,341 children included from the RV1 and RV5 trials, respectively. The 18-month adjusted severe rotavirus gastroenteritis risk was 4.0% (95% confidence interval [CI] = 1.1, 7.1) higher for those receiving their first RV5 dose at <6 versus ≥6 weeks. For RV1, there was a 4.0% (95% CI = 0.0, 8.2) increase in 12-month adjusted risk for a 4- versus 6-week interval between doses. Further analysis revealed those receiving their first RV5 dose at 3–4 and 5–7 weeks had 2.9% (95% CI = 0.8, 5.3) and 1.3% (95% CI = −0.3, 3.0), respectively, higher risk compared with those at 9–12 weeks. Those receiving their first dose at 8 weeks had the lowest risk (RD: −2.6% [95% CI = −5.4, −0.1]) compared with those at 9–12 weeks.

Conclusions:
A modest delay in rotavirus vaccination start and increase in interval between doses may be associated with lower severe rotavirus gastroenteritis risk in low- and middle-income countries.
Age-related Changes in Globe Position
Authors: Shieh Alice C. , Blandford Alexander D. , Hwang Catherine J. , Perry Julian D. 
Published: August 2018

Purpose:
To longitudinally evaluate for changes in globe position as part of the natural aging process.

Methods:
A Cleveland Clinic Foundation imaging database of all head imaging scans performed from 1995 to 2017 was used to identify adults with normal orbits undergoing imaging studies at least 20 years apart. A total of 100 patients (200 globes) who had CT or MRI scans were studied. Globe position was determined by measuring the distance from the anterior aspect of the cornea to the zygomaticofrontal processes baseline. Clinically significant changes in globe position were defined as changes of ≥2 mm posteriorly (enophthalmos) or anteriorly (exophthalmos).

Results:
On average, globe projection decreased by 0.25 ± 2.3 and 0.26 ± 2.2 mm in the right and left eyes, respectively. Clinically significant enophthalmos with age was measured in 55 (27.5%) globes in 35 (35%) individuals, while clinically significant exophthalmos with age was measured in 43 (21.5%) globes in 26 (26%) individuals. The proportion of cases that developed enophthalmos, exophthalmos, or experienced no change were not significantly different from each other (p = 0.26). No patients developed clinically significant enophthalmos in one eye and exophthalmos in the other.

Conclusions:
Adults may develop clinically significant enophthalmos, exophthalmos, or no change in globe position over a 20-year period. This lack of uniform change in globe position with age impacts surgical considerations for treatment of the aging periocular region.
The Importance of Distinguishing Menstrual and Peripheral Blood in Forensic Casework
Authors: Tozzo Pamela , Nespeca Patrizia , Spigarolo Gloria , Caenazzo Luciana 
Published: August 2018

Abstract
This report presents a case of an 18-year-old woman found unconscious by police officers outside a club suspected to be victim of a sexual assault. She was not able to give information about the dynamics of the assault, since she was under the effect of a high amount of alcohol. She affirmed to be virgin.
The forensic genetic analyses were performed on vaginal and rectal swabs as well as bloody-like traces present on the slip. DNA and RNA analysis were performed using a multiplex for 15 autosomal short tandem repeat markers and of 19 primers specific for different tissues, respectively.
No male DNA was identified on vaginal and rectal swabs and on blood spots on the underwear. Blood, vaginal, and skin markers were scored observed in the samples obtained from slip traces and vaginal swab.
The forensic genetic analysis supports the proposition that the victim had a sexual intercourse, in the absence of male biological material, in a case where the victim, altered by high blood alcohol levels, was unable to provide information.
Complications After Scalp Suturing Posttraumatic Avulsion
Authors: Fijałkowska Marta , Antoszewski Bogusław 
Published: August 2018

Abstract
Scalp avulsion is a rare but severe trauma. Most cases of this injury happened as a result of hair entrapment in a high-speed rotating machine. Treatment of scalp avulsion can be challenging. Nowadays, microsurgical scalp replantation has become the treatment of choice. However, there are situations in which replantation or even usage of scalp as composite grafts is not possible. The aim of this paper is to present 2 cases of scalp avulsion, which needed split-thickness skin graft for covering posttraumatic scalp loss. Closing large scalp defects after its avulsion by skin graft is still a viable option, especially when replantation and even usage of scalp as a composite graft is not achievable. Scalp shaving is mandatory before any surgical procedures.
Laparoscopy in Crohn Disease
Authors: Mege Diane , Michelassi Fabrizio 
Published: August 2018

Objective:
To identify preoperative characteristics to help in selecting laparoscopy or laparotomy in Crohn disease (CD).

Summary Background:
Laparoscopy in CD is associated with high rates of conversion.

Methods:
All patients undergoing abdominal surgery for CD in 2004 to 2016 by the senior author. Patients operated by laparoscopy, laparotomy, and converted to open were compared.

Results:
Four hundred fifty-eight procedures were performed in 427 patients [F:M 1:1; median age = 41 (12–95) yrs], through laparotomy (n = 157, 34%) or laparoscopy (n = 301, 66%). Laparotomy rates decreased over time. Concomitant surgical procedures requiring laparotomy continued to dictate an open approach throughout the study. Sixty-five cases (21.6%) required conversion to laparotomy which occurred within 15’ from start of case in 77%. Most common reasons for conversion included dense adhesions (34%), pelvic sepsis with fistulizing disease (26%), large inflammatory mass (18%), and thickened mesentery (9%). After multivariate analysis, predictive factors for conversion included recurrent disease after previous small bowel resection, thickened mesentery, large inflammatory mass, and extensive disease.

Conclusion:
Despite the increasing experience with laparoscopy in CD, one-fifth of selected cases still need conversion. Recurrent disease with dense adhesions, pelvic sepsis with fistulizing disease, large inflammatory mass, and thickened mesentery are all conditions predisposing to a conversion. When the severity of these conditions is known preoperatively or a simultaneous procedure requires a laparotomy, an open approach should be considered; if laparoscopy is selected, conversion to laparotomy can be decided early in the performance of the case.
The Strain Ratio as Obtained by Endoscopic Ultrasonography Elastography Correlates With the Stroma Proportion and the Prognosis of Local Pancreatic Cancer
Authors: Shi Si , Liang Chen , Xu Jin , Meng Qingcai , Hua Jie , Yang Xiujiang , Ni Quanxing , Yu Xianjun 
Published: August 2018

Objective:
The aim of this study was to investigate the association of the strain ratio (SR) with clinicopathologic features and the prognostic value of the SR in local pancreatic cancer.

Background:
The SR as obtained by endoscopic ultrasonography elastography is useful in the differential diagnosis of pancreatic diseases. However, its role in the prognostic prediction of pancreatic cancer remains unknown.

Methods:
A total of 78 resected pancreatic cancer patients and 93 locally advanced pancreatic cancer (LAPC) patients were enrolled in this study according to the inclusion criteria. Masson trichrome staining was used to evaluate the stromal proportion. Survival rates were calculated according to the Kaplan–Meier method and were compared using the log rank test. Multivariate analysis was performed with a Cox regression model.

Results:
The SR was positively associated with the stromal proportion of resected pancreatic cancer (R = 0.768, P < 0.001). High SR was more likely in males (P = 0.039) and was related to perineural invasion (P = 0.022). High SR predicted unfavorable overall survival (OS) relative to low SR (15.4 vs. 25.8 mo, P = 0.017). SR was confirmed as an independent prognostic factor for resected pancreatic cancer based on multivariate analysis (hazard ratio = 1.939, P = 0.020). For LAPC patients who received nab-paclitaxel and gemcitabine, high SR was associated with improved prognosis (OS: 14.9 vs. 11.6 mo, P = 0.045), but this positive association was not observed in patients treated with other gemcitabine-based regimens (OS: 10.7 vs. 12.4 mo, P = 0.478).

Conclusions:
A high SR as obtained by endoscopic ultrasonography elastography was associated with poor prognosis of resected pancreatic cancer but predicted improved survival for LAPC patients treated with the nab-paclitaxel and gemcitabine regimen.
CryoEM structures of MDA5-dsRNA filaments at different stages of ATP hydrolysis
Authors: Yu Qin , Qu Kun , Modis Yorgo 
Published: August 2018

SummaryDouble-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection. Long cytosolic dsRNA is recognized by MDA5. The cooperative assembly of MDA5 into helical filaments on dsRNA nucleates the assembly of a multiprotein type-I-interferon signaling platform. Here, we determined cryoEM structures of MDA5-dsRNA filaments with different helical twists and bound nucleotide analogs, at resolutions sufficient to build and refine atomic models. The structures identify the filament forming interfaces, which encode the dsRNA binding cooperativity and length specificity of MDA5. The predominantly hydrophobic interface contacts confer flexibility, reflected in the variable helical twist within filaments. Mutation of filament-forming residues can result in loss or gain of signaling activity. Each MDA5 molecule spans 14 or 15 RNA base pairs, depending on the twist. Variations in twist also correlate with variations in the occupancy and type of nucleotide in the active site, providing insights on how ATP hydrolysis contributes to MDA5-dsRNA recognition.eTOCStructures of MDA5 bound to double-stranded RNA reveal a flexible, predominantly hydrophobic filament forming interface. The filaments have variable helical twist. Structures determined with ATP and transition state analogs show how the ATPase cycle is coupled to changes in helical twist, the mode of RNA binding and the length of the RNA footprint of MDA5.HighlightsCryoEM structures of MDA5-dsRNA filaments determined for three catalytic statesFilament forming interfaces are flexible and predominantly hydrophobicMutation of filament-forming residues can cause loss or gain of IFN-β signalingATPase cycle is coupled to changes in filament twist and size of the RNA footprint
Physicochemical amino acid properties better describe substitution rates in large populations
Authors: Weber Claudia C. , Whelan Simon 
Published: August 2018

AbstractSubstitutions between chemically distant amino acids are known to occur less frequently than those between more similar amino acids. This knowledge, however, is not reflected in most codon substitution models, which treat all non-synonymous changes as if they were equivalent in terms of impact on the protein. A variety of methods for integrating chemical distances into models have been proposed, with a common approach being to divide substitutions into radical or conservative categories. Nevertheless, it remains unclear whether the resulting models describe sequence evolution better than their simpler counterparts.We propose a parametric codon model that distinguishes between radical and conservative substitutions, allowing us to assess if radical substitutions are preferentially removed by selection. Applying our new model to a range of phylogenomic data, we find differentiating between radical and conservative substitutions provides significantly better fit for large populations, but see no equivalent improvement for smaller populations. Comparing codon- and amino acid models using these same data shows that alignments from large populations tend to select phylogenetic models containing information about amino acid exchangeabilities, whereas the structure of the genetic code is more important for smaller populations.Our results suggest selection against radical substitutions is, on average, more pronounced in large populations than smaller ones. The reduced observable effect of selection in smaller populations may be due to stronger genetic drift making it more challenging to detect preferences. Our results imply an important connection between the life history of a phylogenetic group and the model that best describes its evolution.
Unique morphogenetic signatures define mammalian neck muscles and associated connective tissues
Authors: Heude Eglantine , Tesarova Marketa , Sefton Elizabeth M. , Jullian Estelle , Adachi Noritaka , Grimaldi Alexandre , Zikmund Tomas , Kaiser Jozef , Kardon Gabrielle , Kelly Robert G. , Tajbakhsh Shahragim 
Published: August 2018

ABSTRACTIn vertebrates, head and trunk muscles develop from different mesodermal populations and are regulated by distinct genetic networks. Neck muscles at the head-trunk interface remain poorly defined due to their complex morphogenesis and dual mesodermal origins. Here, we use genetically modified mice to establish a 3D model that integrates regulatory genes, cell populations and morphogenetic events that define this transition zone. We show that the evolutionary conserved cucullaris-derived muscles originate from posterior cardiopharyngeal mesoderm, not lateral plate mesoderm, and we define new boundaries for neural crest and mesodermal contributions to neck connective tissue. Furthermore, lineage studies and functional analysis ofTbx1-andPax3-null mice reveal a unique genetic program for somitic neck muscles that is distinct from that of somitic trunk muscles. Our findings unveil the embryological and developmental requirements underlying tetrapod neck myogenesis and provide a blueprint to investigate how muscle subsets are selectively affected in some human myopathies.
Population size history from short genomic scaffolds: how short is too short?
Authors: Gower Graham , Tuke Jono , Rohrlach AB , Soubrier Julien , Llamas Bastien , Bean Nigel , Cooper Alan 
Published: August 2018

AbstractThe Pairwise Sequentially Markov Coalescent (PSMC), and its extension PSMC′, model past population sizes from a single diploid genome. Both models have been widely applied, even to organisms with scaffold-level genome reference assemblies of limited contiguity. However it is unclear how PSMC and PSMC′ perform on short scaffolds. We evaluatedpsmcandmsmc, implementations of the PSMC and PSMC′ models respectively, on simulated genomes with low contiguity, and compared results to those from fully contiguous data. Simulations with scaffolds from 100 Mb to 10 kb revealed thatpsmcmaintains high accuracy down to lengths of 100 kb, whilemsmcis accurate down to 1 Mb. The discrepancy is not due to differing models, but stems from an implementation detail ofmsmc—homozygous tracts at the ends of scaffolds are discarded, makingmsmcunreliable for low contiguity genomes. We recommend excluding data that are aligned to shorter scaffolds when undertaking demographic inference.