bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Burial to Exhumation: Emplacement and Metamorphism of Mafic Eclogitic Terranes Constrained Through Multimethod Petrochronology, Case Study from the Lévézou Massif (French Massif Central, Variscan Belt)
Authors: Lotout C , Poujol M , Pitra P , Anczkiewicz R , Van Den Driessche J 
Published: April 2020

Abstract
Linking mineral growth and time is required to unravel the evolution of metamorphic rocks. However, dating early metamorphic stages is a challenge due to subsequent retrograde overprinting. A fresh eclogite and a former eclogite retrogressed under amphibolite facies from the southern French Massif Central (Lévézou massif, Variscan belt) were investigated with a large panel of geochronometers (U–Pb in zircon, rutile and apatite, Lu–Hf and Sm–Nd in garnet) in a petrological context tightly constrained by petrographic observations, trace element analyses and phase equilibrium modelling. Both samples recorded similar HP conditions at 18–23 kbar and 680–800°C, whereas the retrogressed eclogite later equilibrated at 8–9·5 kbar and c.600°C. In the retrogressed sample, most of the zircon grains are characterized by negative Eu anomalies and HREE enrichment, and yield an Ordovician U–Pb date of 472·3 ± 1·7 Ma, interpreted as the emplacement age of the mafic protolith. In agreement with other data available for the Variscan belt, and based on zircon trace element record and whole-rock geochemistry, this age is considered to represent the magmatism associated with the extreme thinning of the continental margins during the Ordovician. In the same sample, a few zircon rims show a weaker HREE enrichment and yield a date of 378 ± 5·7 Ma, interpreted as a prograde pre-eclogitic age. Lu–Hf garnet dating from both samples yields identical dates of 357 ± 13 Ma and 358·0 ± 1·5 Ma inferred to approximate the age of the high-pressure metamorphic peak. Fresh and retrogressed samples yield respectively 350·4 ± 7·7 Ma and 352 ± 20 Ma dates for Sm–Nd garnet dating, and 367·8 ± 9·1 Ma and 354·9 ± 9·5 Ma for U–Pb rutile dating. Apatite grains from the retrogressed sample give a mean age of 351·8 ± 2·8 Ma. The similarity between all recorded ages from distinct chronometers and radiometric methods (U–Pb, rutile, apatite; Lu–Hf, garnet; Sm–Nd, garnet) combined with P–T estimations from high-pressure metamorphic rocks equilibrated under different conditions testifies to very fast processes that occurred during the Variscan orogeny, highlighting a major decompression of 15–8·5 kbar in less than 7 Myr, and suggesting mean exhumation rates in excess of 6·3 mm/yr.
FURTHER CLARIFICATIONS ON THE MICRODOSIMETRIC D(Z) MODEL IN RESPONSE TO ‘THE RECENT SUCCESS OF MICRODOSIMETRY’ BY Y.S. HOROWITZ
Authors: Parisi Alessio 
Published: April 2020

Abstract
After a short review of the achievements of the Microdosimetric d(z) Model in describing and predicting the response of luminescent detectors for different exposure conditions, recent comments and suggestions are systematically addressed also in light of more recent findings.
Implementation of a Research‐Based Curriculum in Student Biochemistry Labs: The BASIL Model
Authors: Sikora Arthur 
Published: April 2020

Recently there has been a lot of interest in incorporating and expanding authentic learning in the classroom. The benefits of providing a hands‐on research experiences to undergraduate students has long been known. According to a recent NAS convocation “[Many] factors constrain participation, particularly by members of groups historically underrepresented in STEM fields, many of whom could benefit considerably from being involve in research. BASIL (Biochemistry Authentic Scientific Inquiry Lab) is a model for a discovery based biochemistry lab course. This model along with the associated student and instructor modules was developed as a collaboration of multiple professors working across the country with support from an NSF IUSE grant. This approach takes advantage of the over 3700 unannotated structures in the Protein Data Bank. Using a combination of computational and traditional wet lab skills, students propose and test the likely function of their target protein of interest. One the major goals of the BASIL project is to learn more about how we can help students can learn to conduct authentic scientific inquiry and to assess the roles of faculty members and teaching assistants in this process. This presentation will explain the decisions and steps that new institutions face during a shift from traditional cookbook biochemistry labs featuring predetermined answers to ones that focus on student discovery and highlight the scientific method. Towards the goal of wider adoption, implementation strategies at two separate primarily undergraduate institutions will be highlighted. Currently the BASIL initiative is working to optimize the curriculum and support potential adopters during their transition.Support or Funding InformationThe BASIL project is supported by NSF IUSE 1503811 and 1709170.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
INVESTIGATION OF THE MECHANISTIC DETAILS OF THE RSC1 AND RSC2 SUBUNITS OF THE YEAST RSC CHROMATIN REMODELER
Authors: Obinelo Adaeze 
Published: April 2020

The most basic unit of Eukaryotic nuclear packing is the nucleosome. At this level, DNA is wound around histone octamers; these repeating nucleosome units then wind around one another, amalgamating into chromatin. Though condensed heterochromatin is ideal for nuclear packing, it bars the binding of DNA‐mediating proteins such as polymerases. Therefore in eukaryotes, chromatin remodelers, proteins which relax the nucleosome unit to expose DNA transcripts, are necessary for mediation of vital genetic processes. These genetic implications for chromatin remodelers necessitate an understanding of their structure, and binding mechanism. This is a challenge in the case of RSC, a 17 subunit Saccharomyces cerevisiae chromatin remodeler. Due to its substantial size, its full, detailed structure remains undetermined. Additionally, the explicit mechanism behind RSC function, that is, where it binds to the nucleosome, and when this binding occurs has yet to be demonstrated. In this work, we aim to illuminate the structure/function relationship of the yeast RSC chromatin remodeler. The RSC complex exists in two mutually exclusive isoforms, differing only in one subunit, Rsc1 or Rsc2. We expect that the Rsc1/2 bromodomains are responsible for RSC‐nucleosome binding and that the acetylation of lysine is the sequestering mechanism. Therefore, exploiting the presence of bromodomains at these subunits, we utilize an expanded genetic code in yeast and a crosslinker unnatural amino acid to scan for histone‐Rsc1/2 nucleosomal contacts as a way to identify interfaces at the chromosomal level, in vivo. We scan specifically H3 and H4 due to their high level of lysine acetylation, and use confirmatory western‐blot to identify shifts indicative of successful cross‐linking. We believe that if we can illuminate all RSC‐nucleosome contact in this way that we can create a map of RSC active‐site binding, and can then investigate how this binding changes under varying physiological conditions.Support or Funding InformationResearch conducted with the support of PI Bryan Wilkins and Manhattan College Department of Chemistry.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Burden of Rare Variants in the OTOG Gene in Familial Meniere’s Disease
Authors: Roman-Naranjo Pablo , Gallego-Martinez Alvaro , Soto-Varela Andrés , Aran Ismael , Moleon Maria del Carmen , Espinosa-Sanchez Juan Manuel , Amor-Dorado Juan Carlos , Batuecas-Caletrio Angel , Perez-Vazquez Paz , Lopez-Escamez Jose Antonio 
Published: April 2020

Objectives:
Meniere’s disease (MD) is a rare inner ear disorder characterized by sensorineural hearing loss, episodic vertigo, and tinnitus. Familial MD has been reported in 6 to 9% of sporadic cases, and few genes including FAM136A, DTNA, PRKCB, SEMA3D, and DPT have been involved in single families, suggesting genetic heterogeneity. In this study, the authors recruited 46 families with MD to search for relevant candidate genes for hearing loss in familial MD.

Design:
Exome sequencing data from MD patients were analyzed to search for rare variants in hearing loss genes in a case-control study. A total of 109 patients with MD (73 familial cases and 36 early-onset sporadic patients) diagnosed according to the diagnostic criteria defined by the Barany Society were recruited in 11 hospitals. The allelic frequencies of rare variants in hearing loss genes were calculated in individuals with familial MD. A single rare variant analysis and a gene burden analysis (GBA) were conducted in the dataset selecting 1 patient from each family. Allelic frequencies from European and Spanish reference datasets were used as controls.

Results:
A total of 5136 single-nucleotide variants in hearing loss genes were considered for single rare variant analysis in familial MD cases, but only 1 heterozygous likely pathogenic variant in the OTOG gene (rs552304627) was found in 2 unrelated families. The gene burden analysis found an enrichment of rare missense variants in the OTOG gene in familial MD. So, 15 of 46 families (33%) showed at least 1 rare missense variant in the OTOG gene, suggesting a key role in familial MD.

Conclusions:
The authors found an enrichment of multiplex rare missense variants in the OTOG gene in familial MD. This finding supports OTOG as a relevant gene in familial MD and set the groundwork for genetic testing in MD.
Autogenous Bone Graft With Kirschner Wire Fixation Could Be a Reliable Treatment Option for Scaphoid Nonunion in Adolescents
Authors: Choi Eun Seok , Cha Soo Min , Shin Hyun Dae 
Published: April 2020

Background:
Scaphoid nonunion in adolescents is rare, and most treatments include prolonged immobilization and screw fixation. Many studies have shown that Kirschner wires (K-wires) show comparable outcomes in screw fixation in adult scaphoid nonunion. However, few studies have reported K-wire fixation results in the treatment of adolescent scaphoid nonunion. The purpose of this study was to evaluate the clinical and radiologic results after bone graft and K-wire fixation for scaphoid nonunion in adolescents.

Methods:
We retrospectively reviewed 12 adolescent patients, mean age 15.4 (12 to 17) years, who underwent surgical treatment of scaphoid nonunion. Autogenous bone grafts with K-wire fixation were performed for all patients. Radiologic results, including bone union and degenerative changes, were evaluated with serial radiographs. Clinical results, including range of motion, grip strength, and a visual analogue scale for pain, were assessed.

Results:
All patients received <3 years of postoperative follow-up assessments. Stable bony union was achieved in all patients. Radiologic bony unions were identified at an average of 11.4 weeks postoperatively (range, 9 to 15 wk). The mean active range of motion of the injured wrist at 3 years postoperatively was 215 degrees (range, 185 to 230 degrees). None of the patients were treated for wrist pain or needed medication during follow-up. Three patients experienced intermittent pain (visual analogue scale 1) after heavy work. The grip strength was reduced compared with the uninjured hand (31.8 and 32.8 kg, respectively), but there was no statistically significant difference (P=0.19). All patients had the K-wire removed at 12 weeks postoperatively. There was no degenerative change in the scaphoid at the final follow-up radiograph.

Conclusion:
Autogenous bone graft with K-wire fixation could be a reliable treatment option of scaphoid nonunion in adolescents.

Level of Evidence:
Level IV—retrospective case series.
Combining immunotherapy and radiotherapy in head and neck squamous cell cancers: which perspectives?
Authors: Biau Julian , Bourhis Jean 
Published: April 2020

Purpose of review
The role of the immune system is important in both initiation and development of head and neck cancers. Various immune checkpoints have been discovered that can be exploited by cancer to evade immune mediated destruction. Therefore, immune checkpoint inhibitors have been developed to overcome cancer immune-evasion and are currently in clinical use in head and neck cancers. In addition, the immune system appears to play an important role in the response to radiotherapy. The combination of immunotherapy with radiotherapy may increase the ability to induce immunogenic death by removing the locks blocking the immune system.

Recent findings
Although the antitumour efficacy of radiotherapy is based primarily on the toxicity of DNA damage, studies have suggested that this efficacy is based not only on this local cytotoxic and antiproliferative effect, but also on the interactions between the tumor and its microenvironment that are altered. Thus, the cytotoxic action of radiotherapy on tumor cells provides T lymphocytes with tumor neoantigens, and releases proinflammatory cytokines that promote the immune response. Cell death inducing this type of immune response is called immunogenic death. Therefore, several phase 3 clinical trials are currently ongoing evaluating the combination of radiotherapy and immune checkpoint inhibitors in head and neck cancers.

Summary
Combining immunotherapy and radiotherapy in head and neck cancers is promising. Several phase 3 clinical trials are ongoing that may be practice changing.
A drug-eluting Balloon for the trEatment of coronarY bifurcatiON lesions in the side branch: a prospective multicenter ranDomized (BEYOND) clinical trial in China
Authors: Jing Quan-Min , Zhao Xin , Han Ya-Ling , Gao Ling-Ling , Zheng Yang , Li Zhan-Quan , Yang Ping , Cong Hong-Liang , Gao Chuan-Yu , Jiang Tie-Min , Li Hui , Li Jun-Xia , Wang Dong-Mei , Wang Geng , Cong Zhan-Chun , Zhang Zhong 
Published: April 2020

Abstract

Background
Treatment of coronary bifurcation lesions remains challenging; a simple strategy has been preferred as of late, but the disadvantage is ostium stenosis or even occlusion of the side branch (SB). Only a few single-center studies investigating the combination of a drug-eluting stent in the main branch followed by a drug-eluting balloon in the SB have been reported. This prospective, multicenter, randomized study aimed to investigate the safety and efficacy of a paclitaxel-eluting balloon (PEB) compared with regular balloon angioplasty (BA) in the treatment of non-left main coronary artery bifurcation lesions.

Methods
Between December 2014 and November 2015, a total of 222 consecutive patients with bifurcation lesions were enrolled in this study at ten Chinese centers. Patients were randomly allocated at a 1:1 ratio to a PEB group (n = 113) and a BA group (n = 109). The primary efficacy endpoint was angiographic target lesion stenosis at 9 months. Secondary efficacy and safety endpoints included target lesion revascularization, target vessel revascularization, target lesion failure, major adverse cardiac and cerebral events (MACCEs), all-cause death, cardiac death, non-fatal myocardial infarction, and thrombosis in target lesions. The main analyses performed in this clinical trial included case shedding analysis, base-value equilibrium analysis, effectiveness analysis, and safety analysis. SAS version 9.4 was used for the statistical analyses.

Results
At the 9-month angiographic follow-up, the difference in the primary efficacy endpoint of target lesion stenosis between the PEB (28.7% ± 18.7%) and BA groups (40.0% ± 19.0%) was –11.3% (95% confidence interval: –16.3% to –6.3%, P
superiority <0.0001) in the intention-to-treat analysis, and similar results were recorded in the per-protocol analysis, demonstrating the superiority of PEB to BA. Late lumen loss was significantly lower in the PEB group than in the BA group (–0.06 ± 0.32 vs. 0.18 ± 0.34 mm, P < 0.0001). For intention-to-treat, there were no significant differences between PEB and BA in the 9-month percentages of MACCEs (0.9% vs. 3.7%, P = 0.16) or non-fatal myocardial infarctions (0 vs. 0.9%, P = 0.49). There were no clinical events of target lesion revascularization, target vessel revascularization, target lesion failure, all-cause death, cardiac death or target lesion thrombosis in either group.

Conclusions
In de novo non-left main coronary artery bifurcations treated with provisional T stenting, SB dilation with the PEB group demonstrated better angiographic results than treatment with regular BA at the 9-month follow-up in terms of reduced target lesion stenosis.

Trial registration
ClinicalTrials.gov, NCT02325817; https://clinicaltrials.gov
Self-reported Prostate Cancer Progression Status Is Accurate
Authors: Daugherty Sarah E. , Wright Jonathan L. , Black Amanda , Stanford Janet L. , Hoover Robert , Berndt Sonja I. 
Published: April 2020

Background:
Studies of prostate cancer progression are important for discovering risk factors that may increase the risk of prostate cancer–specific death; however, little is known about the validity of self-reported prostate cancer progression.

Methods:
We conducted a validation study of self-reported prostate cancer progression in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and in a prostate cancer cohort enrolled in a Fred Hutchinson Cancer Research Center (FHCRC)–based study. We calculated measures of validity for self-reported progression, including sensitivity, specificity, positive predictive value, and negative predictive value using medical records as the gold standard.

Results:
Our results suggest that ascertaining prostate cancer progression-related events (i.e., prostate-specific antigen elevation, recurrence, metastasis, and use of secondary treatment) through self-report may be a viable option for identifying men whose disease has progressed after diagnosis or initial therapy, particularly when multiple questions related to progression are included in the assessment (aggregate cluster of questions: sensitivity = 0.76 [PLCO]; 0.93 [FHCRC], specificity = 0.80 [PLCO]; 0.97 [FHCRC]). With an aggregate positive predictive value of 0.50 (PLCO), however, our PLCO results suggest that additional medical record verification of self-reported progression events may be necessary to rule out false positives. Most individuals reporting no evidence of progression-related events, however, were true negatives (aggregate negative predictive value = 0.92 [PLCO]; 0.98 [FHCRC]). Thus, there may be limited utility to investing resources in chart review to confirm self-reported nonevents.

Conclusion:
Ascertaining prostate cancer progression through self-report provides an efficient and valid approach to enhancing existing cancer cohorts with updated data on progression status. See video abstract at, http://links.lww.com/EDE/B658.
Integrating Surveillance Data to Estimate Race/Ethnicity-specific Hysterectomy Inequalities Among Reproductive-aged Women
Authors: Gartner Danielle R. , Delamater Paul L. , Hummer Robert A. , Lund Jennifer L. , Pence Brian W. , Robinson Whitney R. 
Published: April 2020

Background:
Inequalities by race and ethnicity in hysterectomy for noncancerous conditions suggest that some subgroups may be shouldering an unfair burden of procedure-associated negative health impacts. We aimed to estimate race- and ethnicity-specific rates in contemporary hysterectomy incidence that address three challenges in the literature: exclusion of outpatient procedures, no hysterectomy prevalence adjustment, and paucity of non-White and non-Black estimates.

Methods:
We used surveillance data capturing all inpatient and outpatient hysterectomy procedures performed in North Carolina from 2011 to 2014 (N = 30,429). Integrating data from the Behavior Risk Factor Surveillance System and US Census population estimates, we calculated prevalence-corrected hysterectomy incidence rates and differences by race and ethnicity.

Results:
Prevalence-corrected estimates show that non-Hispanic (nH) Blacks (62, 95% confidence interval [CI] = 61, 63) and nH American Indians (85, 95% CI = 79, 93) per 10,000 person-years (PY) had higher rates, compared with nH Whites (45 [95% CI = 45, 46] per 10,000 PY), while Hispanic (20, 95% CI = 20, 21) and nH Asian/Pacific Islander rates (8, 95% CI = 8.0, 8.2) per 10,000 PY were lower than nH Whites.

Conclusion:
Through strategic surveillance data use and application of bias correction methods, we demonstrate wide differences in hysterectomy incidence by race and ethnicity. See video abstract at, http://links.lww.com/EDE/B657.
Drugs in pregnancy
Authors: Andersen Jon T. , Futtrup Tina Bergmann 
Published: April 2020

Summary
Since the thalidomide scandal in the 1960's use of drugs in pregnancy has often been associated with great uncertainty, it can affect both the mother and the fetus. However, the concern may mistakenly lead to nonharmful drugs being attributed teratogenic effects. The drug use during pregnancy and the safety of the most commonly used drugs are in the following being discussed. Furthermore, a practical guide to risk assessment and considerations when initiating a drug treatment is presented.
Oral Fluid to Blood Concentration Ratios of Different Psychoactive Drugs in Samples from Suspected Drugged Drivers
Authors: Bakke Eirin , Høiseth Gudrun , Furuhaugen Håvard , Berg Thomas , Arnestad Marianne , Gjerde Hallvard 
Published: April 2020

Background:The ratio between the concentrations of drugs in the oral fluid and blood (OF/B ratio) reflects the transfer of drugs from blood to oral fluid, which is influenced by several factors such as oral fluid contamination. OF/B drug concentration ratios for psychoactive drugs, including interindividual variation, were investigated in this study. For a portion of the material, oral fluid concentrations in both sides of the mouth were compared.Methods:Samples of whole blood and oral fluid collected using the Intercept device were obtained from 489 suspected drugged drivers. Concentrations of amphetamine, methamphetamine, THC, diazepam, N-desmethyldiazepam, clonazepam, alprazolam, oxazepam, nitrazepam, morphine, buprenorphine, and methadone were determined in blood and oral fluid samples using liquid chromatography–tandem mass spectrometry.Results:Median OF/B ratios were 18.6 for amphetamine, 13.8 for methamphetamine, 3.8 for morphine, 24.8 for buprenorphine, 3.7 for methadone, 0.026 for diazepam, 0.031 for N-desmethyldiazepam, 0.28 for alprazolam, 0.16 for clonazepam, 0.12 for oxazepam, 0.099 for nitrazepam, and 4.3 for THC. Large interindividual variations in OF/B ratios were observed. The median difference in concentrations in oral fluid from both sides of the mouth was less than 20% for all drugs, except THC and buprenorphine, which had median differences of 32%–34%.Conclusions:High OF/B ratios were found for amphetamines and opioids, reflecting a high degree of drug transfer from blood to oral fluid and a longer detection window in oral fluid than in blood. For benzodiazepines, low OF/B ratios were found. Results of the concentration measurements in oral fluid from both sides of the mouth could indicate that some remnants of THC and buprenorphine were present in the oral cavity. The large variations among individuals and between the 2 sides of the mouth suggest that drug concentrations in oral fluid do not accurately reflect drug concentrations in the blood.