bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishing the spectral turnover of blazar PKS 2155−304 as an outcome of radiative losses
Authors: Jagan Sitha K , Sahayanathan S , Misra R , Ravikumar C D , Jeena K 
Published: May 2018

Abstract
The broad-band optical/UV and X-ray spectra of blazars have been often modelled as synchrotron component arising from a broken power-law distribution of electrons. A broken power-law distribution is expected, since the high-energy electrons undergo radiative losses effectively. The change in the energy index should then be ≈1 and corresponds to a spectral index difference of 0.5. However, one of the long outstanding problems has been that the observed index change is significantly different. On the other hand, recent high-quality observations of blazars suggest that their local spectra may not be a power law, instead have a slight curvature and often represented by a log-parabola model. Using XMM–Newtonobservations spanning over 12 yr for the BL Lac PKS 2155−304, we show that the optical/UV and X-ray spectra can be well represented by a broken log-parabola model. Further, we show that such a spectrum can indicate the energy dependence of the electron escape time-scale from the main acceleration zone. This novel approach, besides addressing the observed difference in the photon spectral indices, also tries to explain the spectral turn over in far-UV/soft X-rays as a result of the radiative losses.
The structure of human Nocturnin reveals a conserved ribonuclease domain that represses target transcript translation and abundance in cells
Authors: Abshire Elizabeth T , Chasseur Jennifer , Bohn Jennifer A , Del Rizzo Paul A , Freddolino Lydia , Goldstrohm Aaron C , Trievel Raymond C 
Published: May 2018

Abstract
The circadian protein Nocturnin (NOCT) belongs to the exonuclease, endonuclease and phosphatase superfamily and is most similar to the CCR4-class of deadenylases that degrade the poly-adenosine tails of mRNAs. NOCT-deficient mice are resistant to high-fat diet induced weight gain, and exhibit dysregulation of bone formation. However, the mechanisms by which NOCT regulates these processes remain to be determined. Here, we describe a pair of high-resolution crystal structures of the human NOCT catalytic domain. The active site of NOCT is highly conserved with other exoribonucleases, and when directed to a transcript in cells, NOCT can reduce translation and abundance of that mRNA in a manner dependent on key active site residues. In contrast to the related deadenylase CNOT6L, purified recombinant NOCT lacks in vitro ribonuclease activity, suggesting that unidentified factors are necessary for enzymatic activity. We also find the ability of NOCT to repress reporter mRNAs in cells depends upon the 3′ end of the mRNA, as reporters terminating with a 3′ MALAT1 structure cannot be repressed by NOCT. Together, these data demonstrate that NOCT is an exoribonuclease that can degrade mRNAs to inhibit protein expression, suggesting a molecular mechanism for its regulatory role in lipid metabolism and bone development.
Design of a clinical risk calculator for major clinical outcomes in patients with atherosclerotic renovascular disease
Authors: Vassallo Diana , Foley Robert N , Kalra Philip A 
Published: May 2018

AbstractBackgroundRisk stratification in atherosclerotic renovascular disease (ARVD) can influence treatment decisions and facilitate patient selection for revascularization. In this study, we aim to use variables with the best predictive value to design a risk calculator that can assist clinicians with risk stratification and outcome prediction.MethodsPatients with a radiological diagnosis of ARVD referred to our tertiary renal centre were recruited into this prospective cohort study between 1986 and 2014. Primary clinical endpoints included: death, progression to end-stage kidney disease and cardiovascular events (CVE). A stepwise regression model was used to select variables with the most significant hazard ratio for each clinical endpoint. The risk calculator was designed using Hypertext Markup Language. Survival and CVE-free survival were estimated at 1, 5 and 10 years.ResultsIn total, 872 patients were recruited into the Salford ARVD study with a median follow-up period of 54.9 months (interquartile range 20.2–96.0). Only models predicting death and CVE showed good performance (C-index >0.80). Survival probabilities obtained from the risk calculator show that most patients with ARVD have reduced long-term survival. Revascularization improved outcomes in patients with higher baseline estimated glomerular filtration rate and lower proteinuria but not in those with co-existing comorbidities and higher levels of baseline proteinuria.ConclusionsAlthough this risk calculator requires further independent validation in other ARVD cohorts, this study shows that a small number of easily obtained variables can help predict clinical outcomes and encourage a patient-specific therapeutic approach.
Pharmacokinetics and investigation of optimal dose ertapenem in intermittent hemodialysis patients
Authors: Hsaiky Lama M , Salinitri Francine D , Wong Judy , Jennings Sin-Ling T , Desai Neha H , Lobkovich Alison M , Cha Raymond 
Published: May 2018

Abstract

Background
Previous pharmacokinetic studies demonstrated an increase in serum ertapenem concentrations with decreasing kidney function, including patients receiving renal replacement therapy. This study evaluated the pharmacokinetic parameters of ertapenem in patients receiving hemodialysis.

Methods
This prospective, single-center, open-label study examined the pharmacokinetics of a single intravenous (IV) dose of ertapenem 1 g in seven hospitalized noninfected patients undergoing hemodialysis. Blood samples were collected prior to ertapenem administration and at 0.5, 1, 2, 6, 12 and 48 hours (h) after administration. Ertapenem concentrations were determined by validated liquid chromatography mass spectrometry assay.

Results
Following an IV bolus of 1 g ertapenem, plasma concentrations declined relatively slowly with a mean ±standard deviation (SD) elimination half-life of 19.3 ±6.6 h. Plasma concentrations were similar in all subjects, with maximum mean plasma concentration observed of 343±48 µg/mL postdose. The mean ±SD values for systemic plasma clearance (CL) and volume of distribution at steady state (Vss) were 2±0.5 mL/min and 3295±1187 mL, respectively. The area under the curve for 0 h–∞ (AUCinf) was 7494 ±1424 h•µg/mL. No gender effect was observed and no serious adverse events were reported.

Conclusions
Ertapenem half-life was prolonged in hemodialysis patients. Considering the nonrenal clearance and the expected 70% removal with high-efficacy hemodialysis, the dose of 1 g ertapenem, three times weekly, after hemodialysis may produce pharmacodynamically sufficient exposure for potential antimicrobial efficacy. Further studies are warranted to assess the clinical efficacy and safety of this dose with prolonged duration of therapy.
Supplemental Carbon Dioxide Stabilizes the Upper Airway in Volunteers Anesthetized with Propofol
Authors: Ruscic Katarina Jennifer , Bøgh Stokholm Janne , Patlak Johann , Deng Hao , Simons Jeroen Cedric Peter , Houle Timothy , Peters Jürgen , Eikermann Matthias 
Published: May 2018

Abstract

Background
Propofol impairs upper airway dilator muscle tone and increases upper airway collapsibility. Preclinical studies show that carbon dioxide decreases propofol-mediated respiratory depression. We studied whether elevation of end-tidal carbon dioxide (Petco
2) via carbon dioxide insufflation reverses the airway collapsibility (primary hypothesis) and impaired genioglossus muscle electromyogram that accompany propofol anesthesia.

Methods
We present a prespecified, secondary analysis of previously published experiments in 12 volunteers breathing via a high-flow respiratory circuit used to control upper airway pressure under propofol anesthesia at two levels, with the deep level titrated to suppression of motor response. Ventilation, mask pressure, negative pharyngeal pressure, upper airway closing pressure, genioglossus electromyogram, bispectral index, and change in end-expiratory lung volume were measured as a function of elevation of Petco
2 above baseline and depth of propofol anesthesia.

Results
Petco
2 augmentation dose-dependently lowered upper airway closing pressure with a decrease of 3.1 cm H2O (95% CI, 2.2 to 3.9; P < 0.001) under deep anesthesia, indicating improved upper airway stability. In parallel, the phasic genioglossus electromyogram increased by 28% (23 to 34; P < 0.001). We found that genioglossus electromyogram activity was a significant modifier of the effect of Petco
2 elevation on closing pressure (P = 0.005 for interaction term).

Conclusions
Upper airway collapsibility induced by propofol anesthesia can be reversed in a dose-dependent manner by insufflation of supplemental carbon dioxide. This effect is at least partly mediated by increased genioglossus muscle activity.
Surgical Alteration of Genital Hiatus Size and Anatomic Failure After Vaginal Vault Suspension
Authors: Vaughan Monique H. , Siddiqui Nazema Y. , Newcomb Laura K. , Weidner Alison C. , Kawasaki Amie , Visco Anthony G. , Bradley Megan S. 
Published: May 2018

OBJECTIVE:
To compare anatomic outcomes after native tissue vaginal vault suspension among women categorized by their preoperative and 6-week postoperative genital hiatus size.

METHODS:
We performed a retrospective cohort study in women who underwent native tissue vaginal vault suspension between 2005 and 2015. We defined a wide genital hiatus as 4 cm or greater and a normal genital hiatus as less than 4 cm. We compared three groups: 1) women with a wide genital hiatus preoperatively and 6 weeks postoperatively (persistently wide group), 2) women with a wide genital hiatus preoperatively but normal genital hiatus 6 weeks postoperatively (improved group), and 3) women with a normal genital hiatus preoperatively and 6 weeks postoperatively (stably normal group). Our primary outcome was composite anatomic failure at medium term, defined as either recurrent prolapse beyond the hymen or retreatment for prolapse with surgery or a pessary. Data were analyzed with appropriate bivariate analysis and logistic regression.

RESULTS:
Our study population consisted of 260 women, with 39 of 260 (15.0%) in the persistently wide group, 157 of 260 (60.4%) improved, and 64 of 260 (24.6%) stably normal. Composite anatomic failure was significantly more likely in the persistently wide cohort as compared with the other groups (persistently wide 51.3%, improved 16.6%, stably normal 6.3%, overall P<.01, significant for all pairwise comparisons). These results were consistent when examining the anterior, apical, and posterior compartments individually. In a logistic regression analysis, the persistently wide group was associated with a 4.4-fold increased odds of composite failure (adjusted odds ratio [OR] 4.41, 95% CI 1.99–9.76, P<.01) compared with the improved group and a 15.8-fold increased odds compared with the stably normal group (adjusted OR 15.79, 95% CI 4.66–53.57, P<.01).

CONCLUSION:
Women with a preoperative genital hiatus 4 cm or greater that is not surgically normalized after native tissue vaginal vault suspension are at significantly increased odds of anatomic failure in all compartments.
Perinatal and Peripartum Outcomes in Vanishing Twin Pregnancies Achieved by In Vitro Fertilization
Authors: Romanski Phillip A. , Carusi Daniela A. , Farland Leslie V. , Missmer Stacey A. , Kaser Daniel J. , Walsh Brian W. , Racowsky Catherine , Brady Paula C. 
Published: May 2018

OBJECTIVE:
To compare perinatal and peripartum outcomes of vanishing twin gestations with singleton and dichorionic twin gestations in pregnancies conceived by in vitro fertilization.

METHODS:
We conducted a retrospective cohort study of vanishing twin pregnancies after fresh and cryopreserved autologous in vitro fertilization cycles performed at our institution from 2007 to 2015. Singleton, dichorionic twin, and dichorionic twin pregnancies with spontaneous reduction to one by 14 weeks of gestation (vanishing twins) were included. Analysis was restricted to patients with a live birth delivery at our institution at or beyond 24 weeks of gestation. The primary outcomes were gestational age and birth weight at delivery; secondary outcomes included peripartum morbidities. A subanalysis further differentiated the vanishing twin pregnancies between those in which demise of the twin occurred before compared with after identification of fetal cardiac activity. Logistic regression models were used to estimate the adjusted odds ratio (OR) with a 95% CI of outcomes.

RESULTS:
There were 1,189 pregnancies that met inclusion criteria (798 singleton, 291 twin, and 100 vanishing twin). The mean gestational age at birth and birth weights were 38.6±2.3 weeks of gestation and 3,207±644 g in singleton pregnancies, 35.5±2.7 weeks of gestation and 2,539±610 g in twin pregnancies, and 38.5±1.8 weeks of gestation and 3,175±599 g in vanishing twin pregnancies. When compared with twins, those with a vanishing twin had lower odds of preterm delivery (OR 0.13, 95% CI 0.07–0.23; adjusted OR 0.12, 95% CI 0.07–0.22) and small-for-gestational-age birth weight (OR 0.24, 95% CI 0.13–0.45; adjusted OR 0.14, 95% CI 0.07–0.28).

CONCLUSION:
In pregnancies conceived by in vitro fertilization that progress to at least 24 weeks of gestation, vanishing twin and singleton pregnancies had similar perinatal and peripartum outcomes. Both were significantly better than twin pregnancies.
Trends in Use and Survival Associated With Fertility-Sparing Trachelectomy for Young Women With Early-Stage Cervical Cancer
Authors: Cui Rosa R. , Chen Ling , Tergas Ana I. , Hou June Y. , St. Clair Caryn M. , Neugut Alfred I. , Ananth Cande V. , Hershman Dawn L. , Wright Jason D. 
Published: May 2018

OBJECTIVE:
To assess the trends in use of trachelectomy in the United States and to examine the outcomes of the procedure compared with hysterectomy in young women with cervical cancer.

METHODS:
Data were analyzed from women younger than 50 years of age with stage IA2–IB2 cervical cancer treated with hysterectomy or trachelectomy from 2004 to 2014 who were registered in the National Cancer Database. After propensity score matching, we used Cox proportional hazard models to examine the association between treatment and survival.

RESULTS:
We identified 15,150 patients with cervical cancer, including 14,714 (97.1%) who underwent hysterectomy and 436 (2.9%) who underwent trachelectomy. Trachelectomy rates increased from 1.5% in 2004 to 3.8% by 2014 (P<.001). The greatest increase in the rate of trachelectomy was seen in women younger than 30 years of age (4.6% in 2004 to 17.0% in 2014, P<.001). Among women who underwent trachelectomy, 29.6% had tumors greater than 2 cm in diameter. In a multivariable model, younger women and those more recently diagnosed were more likely to undergo trachelectomy, whereas Medicaid recipients (risk ratio 0.39, 95% CI 0.28–0.54) and the uninsured (risk ratio 0.67, 95% CI 0.45–1.00) were less likely to undergo trachelectomy. After propensity score matching, there was no association between trachelectomy and the risk of mortality (hazard ratio 1.24, 95% CI 0.70–2.22) (mortality rate was 6.0% for hysterectomy vs 5.2% for trachelectomy). Similarly, 5-year survival rates were similar between trachelectomy and hysterectomy for all of the stages examined.

CONCLUSIONS:
Use of trachelectomy for early-stage cervical cancer has increased in the United States, particularly among women younger than 30 years of age. Within this population, survival is similar for trachelectomy and hysterectomy.
Total Laparoscopic Hysterectomy Under Regional Anesthesia
Authors: Moawad Nash S. , Santamaria Flores Estefania , Le-Wendling Linda , Sumner Martina T. , Enneking F. Kayser 
Published: May 2018

BACKGROUND:
Laparoscopic hysterectomies comprise a large proportion of all hysterectomies in the United States. Procedures completed under regional anesthesia pose a number of benefits to patients, but laparoscopic hysterectomies traditionally have been performed under general anesthesia. We describe a case of total laparoscopic hysterectomy under epidural anesthesia with the patient fully awake.

CASE:
A 51-year-old woman with abnormal uterine bleeding underwent an uncomplicated total laparoscopic hysterectomy, bilateral salpingectomy, and excision of endometriosis. The procedure was completed under epidural anesthesia without intravenous sedation or systemic narcotics. Pneumoperitoneum with a pressure of 12 mm Hg and Trendelenburg to 15° allowed for adequate visualization. Anesthesia was achieved with midthoracic and low lumbar epidural catheters. Bilevel positive airway pressure was used for augmentation of respiratory function.

CONCLUSION:
With a committed patient, adequate planning, and knowledge of the potential intraoperative complications, regional anesthesia is an option for select women undergoing laparoscopic hysterectomy.
Risk of Gynecologic Cancer According to the Type of Endometriosis
Authors: Saavalainen Liisu , Lassus Heini , But Anna , Tiitinen Aila , Härkki Päivi , Gissler Mika , Pukkala Eero , Heikinheimo Oskari 
Published: May 2018

OBJECTIVE:
To assess the risks of gynecologic cancer according to the type of endometriosis in women with surgically verified endometriosis.

METHODS:
This is a population-based study of women with surgically verified endometriosis retrieved from the Finnish Hospital Discharge Register 1987–2012 (N=49,933); the subtypes of ovarian (n=23,210), peritoneal (n=20,187), and deep infiltrating (n=2,372) endometriosis were analyzed separately. Gynecologic cancers were obtained from the Finnish Cancer Registry. The outcome measure was the standardized incidence ratio (95% CI) calculated as the ratio between the observed to the expected number of cancers and defined for each gynecologic cancer and further stratified according to the histology, follow-up time since surgery, and age at follow-up. The follow-up was 838,685 person-years, and the Finnish female population served as the reference.

RESULTS:
Endometriosis was associated with increased risk of ovarian cancer (standardized incidence ratio 1.76 [95% CI 1.47–2.08]), especially with endometrioid (3.12 [2.15–4.38]) and clear cell (5.17 [3.20–7.89]) histologic type and to a lesser extent with serous type (1.37 [1.02–1.80]). The risk of ovarian cancer was highest among women with ovarian endometriosis and especially for endometrioid (4.72 [2.75–7.56]) and clear cell (10.1 [5.50–16.9]) ovarian cancer, occurring 5–10 years after the index surgery. The overall risk of ovarian cancer was not increased among women with peritoneal and deep infiltrating endometriosis. However, peritoneal endometriosis was associated with a twofold increase in risk of endometrioid histology. The risk of endometrial cancer was not altered in the entire cohort. The standardized incidence ratio for precancerous cervical lesions was 0.81 (0.71–0.92) and for invasive squamous cell carcinoma of the cervical cancer 0.46 (0.20–0.91).

CONCLUSION:
The excess risk of ovarian cancer among women with ovarian endometriosis translates into two excess cases per 1,000 patients followed for 10 years. Acknowledging these risks is important when planning long-term management of women with endometriosis.
PD-L1 Expression is Increased in Metastasizing Squamous Cell Carcinomas and Their Metastases
Authors: García-Díez Irene , Hernández-Ruiz Eugenia , Andrades Evelyn , Gimeno Javier , Ferrándiz-Pulido Carla , Yébenes Mireia , García-Patos Vicenç , Pujol Ramón M. , Hernández-Muñoz Inmaculada , Toll Agustí 
Published: May 2018

Abstract:
Programmed cell death ligand 1 (PD-L1) expression by tumor cells plays an important role in the inhibition of T cell–mediated immune response in cancer. PD-L1 expression by tumor cells has been linked to poor prognosis in a wide variety of cancers. However, PD-L1 expression in cutaneous squamous cell carcinoma (cSCC) has been scarcely studied, and its role as a prognosis biomarker remains controversial. The association of PD-L1 expression and the metastatic risk in a series of cSCC was assessed. PD-L1 and CD8 immunostainings of full excision sections of 99 primary tumors and 24 lymphatic metastases were semiquantitatively evaluated. Primary cSCCs were grouped according to the development of lymphatic metastatic spread [metastasizing squamous cell carcinoma (MSCC)] (n = 48) or the absence of progression [nonmetastasizing squamous cell carcinoma (NMSCC)] (n = 51). PD-L1–positive expression (cut off ≥1%) was found in 26% NMSCCs and in 50% MSCCs (P = 0.02). PD-L1 association with an increased metastatic risk was confirmed in the multivariate analysis (P < 0.05), along with the following features: recurrence, poor differentiation, and perineural invasion. Ninety percent of the metastases of PD-L1–positive tumors were also positive for PD-L1, displaying a trend toward a higher PD-L1 expression when compared with their primary tumors (P = 0.058). No significant differences in the peritumoral inflammatory infiltrate or in the expression of CD8 were found between metastasizing and nonmetastasizing primary tumors. Our results suggest that PD-L1 may play a relevant role in metastatic spread and may be a candidate prognostic biomarker in cSCC.
Two Cases of Chronic Candidiasis in Keratitis–Ichthyosis–Deafness Syndrome
Authors: Bartenstein Diana , Chung Hye Jin , Hussain Sadaf 
Published: May 2018

Abstract:
Keratitis–ichthyosis–deafness (KID) syndrome is a rare genodermatosis that typically results from mutations of the GJB2 gene or, less commonly, the GJB6 gene. Patients with KID syndrome are at higher risk of malignancy and infections. Here, we present 2 patients with KID syndrome who developed verrucous plaques. Given that patients with KID syndrome are at high risk of developing squamous cell carcinoma, biopsies were performed. Both cases revealed histologic findings of marked papillomatous epidermal hyperplasia with numerous fungal spores and pseudohyphae in the stratum corneum. For one case, daily oral fluconazole was initiated. The patient demonstrated dramatic resolution of his foot plaques over the course of 2 years. These cases highlight that, for the dermatopathologist, chronic fungal infection should be sought for verrucous plaques in patients with KID syndrome as, if present, this finding may alter treatment and quality of life.
Impact of Mohs Micrographic Surgery on Tumor Staging of Cutaneous Squamous Cell Carcinoma: A Comparison of the 7th and 8th Editions of the American Joint Committee on Cancer Guidelines
Authors: Montuno Michael A. , Brown Brandon , Konda Sailesh , Motaparthi Kiran 
Published: May 2018

BACKGROUND
Based on current AJCC-7 guidelines for staging cutaneous squamous cell carcinoma (cSCC), patients with T2 tumor staging represent a prognostically heterogeneous group. The new AJCC-8 guidelines seek to provide improved stratification by inclusion of independent risk factors in the T3 category. These features may be identified in tissue stages during Mohs micrographic surgery (MMS). Thus, low-risk cSCC may be upstaged after MMS, impacting prognosis, additional evaluation, and adjuvant nonsurgical treatment.

OBJECTIVE
To examine the impact of MMS on cSCC staging under AJCC-7 and AJCC-8 guidelines.

MATERIALS AND METHODS
The medical record was queried for patients who underwent MMS for cSCC. Data were recorded for 190 MMS specimens and corresponding biopsies. Tumor staging according to AJCC-7 and AJCC-8 was assigned.

RESULTS
High-risk histologic features are more likely identified with MMS than biopsies. Cutaneous squamous cell carcinoma was equally likely to be upstaged during MMS under both AJCC-7 and AJCC-8, with 10.5% being classified as AJCC-8 T3. Seventy percent of these were only classified as T3 after MMS. Upstaging to T3 during MMS under AJCC-8 is less likely than upstaging to T2 under AJCC-7.

CONCLUSION
Mohs surgeons have a significant impact on accurate staging of high-risk cSCC. AJCC-8 improves risk stratification of cSCC.