bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Alcohol Industry Action to Reduce the Harmful Use of Alcohol: Case Study from Great Britain
Authors: Anderson Peter , Jané Llopis Eva , Rehm Jürgen
Published: April 2020

Aims

To describe a case study in the British market of one of the global beer-producing companies that has set a target to increase the proportion of its products with an alcohol by volume (ABV) of 3.5% or less, and to reduce the mean ABV of its beer products.

Methods

Descriptive statistics and time-series analyses using Kantar Worldpanel’s British household purchase data for 2015–2018.

Results

As assessed by British household purchase data, 15.7% of the company’s beer products had an ABV of 3.5% or less in 2018, compared with 8.8% in 2015. The mean ABV of its beer products dropped from 4.69 in 2015 to 4.55 in 2018. Associated with these changes, the increase in purchased grams of alcohol in all beer that occurred during 2015–2016 (standardized coefficient = 0.007), plateaued during 2017 (standardized coefficient = −0.006) and decreased during 2018 (standardized coefficient = −0.034). Similar findings applied to the purchased grams of alcohol in beer other than ABI beer, suggesting some switching from other beer products to ABI products; and in all alcohol, suggesting, on balance, no overall switching to higher strength products. Greater decreases in purchases were found in the younger age groups, the highest purchasing households in terms of grams of alcohol, class groups D and E, and Scotland; there was no clear pattern by household income.

Conclusions

The proportion of the company’s beer purchased in Great Britain that had an ABV of 3.5% or less increased since the launch of the target, and the mean ABV of its beer products decreased. The changes were associated with reduced purchases of grams of alcohol within its beer products. The associated reductions in purchases of alcohol in all beer and in all alcohol products suggest no evidence of overall switching to other higher strength beer or alcohol products. Other beer-producing companies should undertake similar initiatives. A regulatory tax environment should be introduced to ensure a level-playing field favouring lower alcohol concentration across all beer and other alcohol products.
The OMEGA-NET International Inventory of Occupational Cohorts
Authors: Kogevinas Manolis , Schlünssen Vivi , Mehlum Ingrid S , Turner Michelle C
Published: April 2020

In a recent count of cohort studies in Europe capturing information on occupation and/or occupational exposures, we estimated that there are more than 60 major studies with some type of occupational information that enrolled over 30 million persons. With few exceptions there have been no large-scale analyses systematically combining cohorts from this extraordinary resource. We present the development of an inventory of cohorts with occupational information in Europe and internationally and describe the online interactive tool with detailed information on existing cohorts. The OMEGA-NET inventory can be accessed at http://occupationalcohorts.net/ includes cohorts, case-control studies nested within cohorts and intervention studies that are active or can substantiate that their data are potentially accessible; that include data on occupation and/or industry or at least one occupational exposure; and that have at least one follow-up, either already conducted or planned. We expect that this open access inventory will be an important prerequisite for use of this resource of existing studies for research and policy development.
Defense against predators incurs high reproductive costs for the aposematic moth Arctia plantaginis
Authors: Lindstedt Carita , Suisto Kaisa , Burdfield-Steel Emily , Winters Anne E , Mappes Johanna
Published: April 2020

To understand how variation in warning displays evolves and is maintained, we need to understand not only how perceivers of these traits select color and toxicity but also the sources of the genetic and phenotypic variation exposed to selection by them. We studied these aspects in the wood tiger moth Arctia plantaginis, which has two locally co-occurring male color morphs in Europe: yellow and white. When threatened, both morphs produce defensive secretions from their abdomen and from thoracic glands. Abdominal fluid has shown to be more important against invertebrate predators than avian predators, and the defensive secretion of the yellow morph is more effective against ants. Here, we focused on the morph-linked reproductive costs of secretion of the abdominal fluid and quantified the proportion of phenotypic and genetic variation in it. We hypothesized that, if yellow males pay higher reproductive costs for their more effective aposematic display, the subsequent higher mating success of white males could offer one explanation for the maintenance of the polymorphism. We first found that the heritable variation in the quantity of abdominal secretion was very low (h2 = 0.006) and the quantity of defensive secretion was not dependent on the male morph. Second, deploying the abdominal defensive secretion decreased the reproductive output of both color morphs equally. This suggests that potential costs of pigment production and chemical defense against invertebrates are not linked in A. plantaginis. Furthermore, our results indicate that environmentally induced variation in chemical defense can alter an individual’s fitness significantly.
Blood-based multi-tissue gene expression inference with Bayesian ridge regression
Authors: Xu Wenjian , Liu Xuanshi , Leng Fei , Li Wei
Published: April 2020

Motivation

Gene expression profiling is widely used in basic and cancer research but still not feasible in many clinical applications because tissues, such as brain samples, are difficult and not ethnical to collect. Gene expression in uncollected tissues can be computationally inferred using genotype and expression quantitative trait loci. No methods can infer unmeasured gene expression of multiple tissues with single tissue gene expression profile as input.

Results

Here, we present a Bayesian ridge regression-based method (B-GEX) to infer gene expression profiles of multiple tissues from blood gene expression profile. For each gene in a tissue, a low-dimensional feature vector was extracted from whole blood gene expression profile by feature selection. We used GTEx RNAseq data of 16 tissues to train inference models to capture the cross-tissue expression correlations between each target gene in a tissue and its preselected feature genes in peripheral blood. We compared B-GEX with least square regression, LASSO regression and ridge regression. B-GEX outperforms the other three models in most tissues in terms of mean absolute error, Pearson correlation coefficient and root-mean-squared error. Moreover, B-GEX infers expression level of tissue-specific genes as well as those of non-tissue-specific genes in all tissues. Unlike previous methods, which require genomic features or gene expression profiles of multiple tissues, our model only requires whole blood expression profile as input. B-GEX helps gain insights into gene expressions of uncollected tissues from more accessible data of blood.

Availability and implementation

B-GEX is available at https://github.com/xuwenjian85/B-GEX.

Supplementary information

Supplementary data are available at Bioinformatics online.
BAI1 acts as a tumor suppressor in lung cancer A549 cells by inducing metabolic reprogramming via the SCD1/HMGCR module
Authors: Liu Lei , Chai Li , Ran Jingjing , Yang Ying , Zhang Li
Published: April 2020

Brain-specific angiogenesis inhibitor 1 (BAI1) is an important tumor suppressor in multiple cancers. However, the mechanisms behind its anti-tumor activity, particularly the relationship between BAI1 and metabolic aberrant of a tumor, remained unveiled. This study aimed to investigate whether BAI1 could inhibit biological functions in lung cancer A549 cells and the critical regulating molecules that induce metabolic reprogramming. Immunohistochemistry staining was performed to analyze whether variations in the expression of BAI1 in tumor tissues contributes to poor prognosis of lung cancer. Overexpressed BAI1 (BAI1-OE-A549) and control (Vector-NC-A549) were generated by lentiviral transfection. Biological function assays (proliferation, apoptosis, colony formation, invasion and in vivo metastasis), as well as metabolic reprogramming (by the Warburg effect and the glycolytic rate), were performed in both groups. Our results indicated that lower levels of BAI1 contributed to poor prognosis of lung cancer patients. Furthermore, overexpressed of BAI1 dramatically inhibited proliferation, migration, invasion, colony formation and in vivo metastasis of A549 cells. The Warburg effect and the Seahorse assay revealed that BAI1-OE induced metabolism reprogramming by inhibiting the Warburg effect and glycolysis. Further exploration indicated that BAI1 induced metabolic reprogramming by upregulating stearoyl-CoA desaturase 1 (SCD1) and inhibited 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Our study revealed a novel mechanism through which BAI1 acted as tumor suppressor by inducing metabolic reprogramming via the SCD1 and HMGCR module.
The Impact of Different Types of Violence on Ebola Virus Transmission During the 2018–2020 Outbreak in the Democratic Republic of the Congo
Authors: Kelly John Daniel , Wannier Sarah Rae , Sinai Cyrus , Moe Caitlin A , Hoff Nicole A , Blumberg Seth , Selo Bernice , Mossoko Mathais , Chowell-Puente Gerardo , Jones James Holland , Okitolonda-Wemakoy Emile , Rutherford George W , Lietman Thomas M , Muyembe-Tamfum Jean Jacques , Rimoin Anne W , Porco Travis C , Richardson Eugene T
Published: April 2020

Background

Our understanding of the different effects of targeted versus nontargeted violence on Ebola virus (EBOV) transmission in Democratic Republic of the Congo (DRC) is limited.

Methods

We used time-series data of case counts to compare individuals in Ebola-affected health zones in DRC, April 2018–August 2019. Exposure was number of violent events per health zone, categorized into Ebola-targeted or Ebola-untargeted, and into civilian-induced, (para)military/political, or protests. Outcome was estimated daily reproduction number (Rt) by health zone. We fit linear time-series regression to model the relationship.

Results

Average Rt was 1.06 (95% confidence interval [CI], 1.02–1.11). A mean of 2.92 violent events resulted in cumulative absolute increase in Rt of 0.10 (95% CI, .05–.15). More violent events increased EBOV transmission (P = .03). Considering violent events in the 95th percentile over a 21-day interval and its relative impact on Rt, Ebola-targeted events corresponded to Rt of 1.52 (95% CI, 1.30–1.74), while civilian-induced events corresponded to Rt of 1.43 (95% CI, 1.21–1.35). Untargeted events corresponded to Rt of 1.18 (95% CI, 1.02–1.35); among these, militia/political or ville morte events increased transmission.

Conclusions

Ebola-targeted violence, primarily driven by civilian-induced events, had the largest impact on EBOV transmission.
This IsThe ShackThat Job Built: Theodicy and Polytheism in William Paul Young’s Evangelical Bestseller
Authors: Douglas Christopher
Published: April 2020

William Paul Young’s bestselling evangelical novel The Shack (2007) is a twenty-first century re-imagining of the Biblical book of Job, a re-imagining that strangely multiplies the number of divine beings responding to the problem of suffering. I argue that Young has inadvertently rediscovered the ancient Israelite polytheism of three thousand years ago, for the simple reason that justifying the gods’ ways to humans is an easier task than justifying God’s ways to humans. A “deep time” approach to contemporary religiously-interested literature illuminates the Biblical and Ancient Near East texts with which The Shack is in dialogue. Recent critical-historical Bible scholarship, meanwhile, uncovers the pantheon of gods worshipped in ancient Israelite religion, gods whose genealogical traces lead us to The Shack’s divine characters.
Nurse workarounds in the electronic health record: An integrative review
Authors: Fraczkowski Dan , Matson Jeffrey , Lopez Karen Dunn
Published: April 2020

Objective

The study sought to synthesize published literature on direct care nurses’ use of workarounds related to the electronic health record.

Materials and Methods

We conducted an integrative review of qualitative and quantitative peer-reviewed research through a structured search of Academic Search Complete, EBSCO Cumulative Index of Nursing and Allied Health Literature (CINAHL), Embase, Engineering Village, Ovid Medline, Scopus, and Web of Science. We systematically applied exclusion rules at the title, abstract, and full article stages and extracted and synthesized their research methods, workaround classifications, and probable causes from articles meeting inclusion criteria.

Results

Our search yielded 5221 results. After removing duplicates and applying rules, 33 results met inclusion criteria. A total of 22 articles used qualitative approaches, 10 used mixed methods, and 1 used quantitative methods. While researchers may classify workarounds differently, they generally fit 1 of 3 broad categories: omission of process steps, steps performed out of sequence, and unauthorized process steps. Each study identified probable causes, which included technology, task, organizational, patient, environmental, and usability factors.

Conclusions

Extensive study of nurse workarounds in acute settings highlights the gap in ambulatory care research. Despite decades of electronic health record development, poor usability remains a key concern for nurses and other members of care team. The widespread use of workarounds by the largest group of healthcare providers subverts quality health care at every level of the healthcare system. Research is needed to explore the gaps in our understanding of and identify strategies to reduce workaround behaviors.
Alleged predisposing dietary factors fail to increase the incidence of osteochondrosis-like lesions in growing pigs at 14 and 24 wk of age
Authors: Grez-Capdeville Mariola , Gross Nicole , Baker Joni C , Shutter Jennifer A , Haas Amanda R , Wilson Mark E , Crenshaw Thomas D
Published: April 2020

Early lesions of osteochondrosis (OC) are exhibited by regions of cartilage retention along the growth plate and articular cartilage. Progression of OC lesions may impair locomotion and necessitate euthanasia in adherence to animal welfare guides. Little is known about the role of nutrition in the initiation and early stages of OC. However, dietary components are commonly implicated as predisposing factors. In this study, diets were altered as an attempt to induce early stage OC lesions under controlled conditions. At 8 wk of age, 96 crossbred gilts (body weight [BW] = 17.4 ± 0.18 kg) were randomly assigned to one of four corn-soybean meal-based diets (four pens per diet, six pigs per pen) to assess diet effects on the number and volume of OC lesions in the distal femur. Diets included a non-pelleted control diet (Ctl); Ctl plus 20% glucose (Glc); the Ctl with increased concentrations of lysine, Ca, and P (+CaP); and the +CaP diet in a pelleted form (PEL). Femurs were collected from pigs euthanized at either 14-wk (Wk 14) or 24-wk (Wk 14) of age for assessments of OC lesions. Based on a mixed model analysis with pen as the experimental unit, dietary treatments did not affect final BW (129.3 ± 3.8 kg) or average daily gain (ADG) (1.00 ± 0.03 kg/d) over the trial. As expected, pigs fed PEL and Glc diets were more efficient (P < 0.05) in feed conversion compared with Ctl and +CaP. Using femurs as the experimental unit at Wk 14 (collected from two of the six pigs per pen), bone mineral content, determined by dual-energy x-ray absorptiometry scans, was greater (P < 0.05) in pigs fed +CaP and PEL than Ctl or Glc diets; however, only +CaP group differed (P < 0.05) at Wk 24 (collected from four pigs per pen). Computed tomography (CT) scans of femurs were reconstructed as three-dimensional images to allow detection of the number, volume, and surface area of lesions in distal growth plates. At Wk 14, pigs fed Ctl had fewer number of lesions (P < 0.05); however, no differences were detected among dietary treatments in lesion volume or lesion surface area. Pigs had fewer lesions at Wk 24 than Wk 14; however, differences were not detected among dietary treatments. At Wk 24, pigs fed Ctl diets had the greatest lesion volume among dietary treatments (P < 0.05). In conclusion, none of the pigs exhibited symptoms of lameness regardless of dietary treatment or OC lesion traits. Diet modifications due to pelleting or inclusion of rapidly digestible ingredients, such as glucose, did not increase prevalence or size of OC lesions. Image analysis of CT scans was a reliable method to quantify the number, size, and location of OC lesions.
Effects of increased lysine and energy feeding duration prior to parturition on sow and litter performance, piglet survival, and colostrum quality
Authors: Gourley Kiah M , Swanson Analicia J , DeRouchey Joel M , Tokach Mike D , Dritz Steve S , Goodband Robert D , Woodworth Jason C
Published: April 2020

A total of 467 sows were used to evaluate the effect of feeding duration of increased lysine (Lys) and metabolizable energy (ME) prior to farrowing on sow and litter performance, piglet survival, and colostrum quality. Sows were blocked by body weight (BW) and parity category on day 106 of gestation and allotted to one of three dietary regimens starting on day 107 of gestation: 1) Control: 2.0 kg/d gestation feed (12.5 g standardized ileal digestible [SID] Lys and 6.5 Mcal ME) until day 113 of gestation, then 2.7 kg/d lactation feed (28 g SID Lys and 9.4 Mcal ME) until parturition; 2) 2.0 kg/d gestation feed (12.5 g SID Lys and 6.5 Mcal ME) until day 113 of gestation, then 3.8 kg/d lactation feed (40 g SID Lys and 13.3 Mcal ME) until parturition; or 3) 3.8 kg/d lactation feed (40 g SID Lys and 13.3 Mcal ME) until parturition. Data were analyzed for treatment within parity effects using the GLIMMIX procedure of SAS. Increasing the duration of feeding additional Lys and ME increased (P < 0.05) sow weight gain from day 106 to 113. Sow backfat gain from day 106 to 113 of gestation increased (P < 0.05) in gilts and sows fed 3.8 kg/d of the lactation diet starting on day 107 vs. the control regimen. Average total born and born alive piglet birth weight (BiWt) were greater (P < 0.05) in gilts fed 3.8 kg/d lactation diet starting on day 107 or 113 vs. control, with no evidence (P > 0.05) for the difference in piglet BiWt in sows or weaning weight in gilts and sows. Piglet mortality after cross-fostering to weaning was decreased (P < 0.05) in sows fed 3.8 kg/d lactation diet starting on day 113 vs. control or increased lactation diet starting on day 107 but not in gilts. Litter gain from cross-foster to weaning was decreased (P < 0.05) in gilts fed 3.8 kg/d lactation diet starting on day 107 compared with control, with no evidence for difference in sows. Colostrum immunoglobulin G was increased (P < 0.05) in gilts and sows fed 3.8 kg/d of the lactation diet starting on day 113 compared with control. There was no evidence that dietary regimen influenced (P > 0.05) piglet colostrum intake or colostrum yield. There was also no evidence for difference (P > 0.05) among regimens in wean-to-estrus interval, subsequent farrowing rate, or subsequent litter characteristics. In conclusion, feeding increased Lys and ME prior to farrowing increased BW and backfat. Feeding increased Lys and ME when gilts were moved into the farrowing room increased BiWt, but reduced litter growth to weaning, with little evidence that sow performance was influenced in this study.
The Affordable Care Act’s Medicaid Expansion and Impact Along the Cancer-Care Continuum: A Systematic Review
Authors: Moss Haley A , Wu Jenny , Kaplan Samantha J , Zafar S Yousuf
Published: April 2020

Background

Health reform and the merits of Medicaid expansion remain at the top of the legislative agenda, with growing evidence suggesting an impact on cancer care and outcomes. A systematic review was undertaken to assess the association between Medicaid expansion and the goals of the Patient Protection and Affordable Care Act in the context of cancer care. The purpose of this article is to summarize the currently published literature and to determine the effects of Medicaid expansion on outcomes during points along the cancer care continuum.

Methods

A systematic search for relevant studies was performed in the PubMed/MEDLINE, EMBASE, Scopus, and Cochrane databases. Three independent observers used an abstraction form to code outcomes and perform a quality and risk of bias assessment using predefined criteria.

Results

A total of 48 studies were identified. The most common outcomes assessed were the impact of Medicaid expansion on insurance coverage (23.4% of studies), followed by evaluation of racial and/or socioeconomic disparities (17.4%) and access to screening (14.5%). Medicaid expansion was associated with increases in coverage for cancer patients and survivors as well as reduced racial- and income-related disparities.

Conclusions

Medicaid expansion has led to improved access to insurance coverage among cancer patients and survivors, particularly among low-income and minority populations. This review highlights important gaps in the existing oncology literature, including a lack of studies evaluating changes in treatment and access to end-of-life care following implementation of expansion.
Unusual pulmonary vein variant in a patient with right upper lobe lung cancer
Authors: Tobita Rika , Nakamura Ryota , Inage Yoshihisa
Published: April 2020

It is essential to understand individual pulmonary anatomy, and the relationship between the tumor and surrounding organ, when lung resection is conducted. Recently, many anomalous pulmonary venous variations have been detected using three-dimensional computed tomography (3D-CT). Herein, we report the case of a 62-year-old women with lung cancer and an anomalous right upper lobe pulmonary vein that drained into the left atrium between the pulmonary artery and bronchus. Preoperative 3D-CT clearly demonstrated the anomalous pulmonary vein, and we safely performed lung resection by thoracoscopic surgery. Therefore, 3D-CT images can help ensure the safety of patients with aberrant vasculature during lung resection.
Dynamical friction-driven orbital circularization in rotating discs: a semi-analytical description
Authors: Bonetti Matteo , Bortolas Elisa , Lupi Alessandro , Dotti Massimo , Raimundo Sandra I
Published: April 2020

We present and validate a novel semi-analytical approach to study the effect of dynamical friction (DF) on the orbits of massive perturbers in rotating stellar discs. We find that DF efficiently circularizes the orbit of co-rotating perturbers, while it constantly increases the eccentricity of counter-rotating ones until their angular momenta reverse, then once again promoting circularization. Such ‘drag toward circular co-rotation’ could shape the distribution of orientations of kinematically decoupled cores in disc galaxies, naturally leading to the observed larger fraction of co-rotating cores.
Latent Trajectories and Profiles of Commercial Cigarette Smoking Frequency From Adolescence to Young Adulthood Among North American Indigenous People
Authors: Hautala Dane , Sittner Kelley , Walls Melissa
Published: April 2020

Introduction

North American Indigenous people (ie, American Indian/Alaska Native and Canadian First Nations) have the highest rates of commercial cigarette smoking, yet little is known about long-term trajectories of use among this population. The purpose of this study is to examine heterogeneous trajectories and profiles of Indigenous cigarette use frequency from early adolescence (mean age: 11.1 years) to young adulthood (mean age: 26.3 years).

Aims and Methods

Data come from a nine-wave prospective longitudinal study spanning early adolescence through young adulthood among Indigenous people in the Upper Midwest of the United States and Canada (N = 706). Smoking frequency was examined at each wave, and latent class growth analysis was used to examine heterogeneous patterns. Early adolescent and young adult demographics and smoking-related characteristics were examined across these latent trajectory groups.

Results

In young adulthood, 52% of participants smoked daily/near-daily, and an additional 10% smoked weekly or monthly. Four latent trajectory groups emerged: low/non-smokers (35.2%) who had low probabilities of smoking across the study; occasional smokers (17.2%) who had moderate probabilities of smoking throughout adolescence and declining probabilities of smoking into young adulthood; mid-adolescent onset smokers (21.6%) who showed patterns of smoking onset around mid-adolescence and escalated to daily use in young adulthood; and early-adolescent onset smokers (25.9%) who showed patterns of onset in early adolescence and escalated to stable daily use by late adolescence.

Conclusions

The findings suggest multiple critical periods of smoking risk, as well as a general profile of diverse smoking frequency patterns, which can inform targeted intervention and treatment programming.

Implications

Nearly two-thirds (62%) of this sample of Indigenous people were current smokers by early adulthood (mean age = 26.3 years), which is substantially higher than national rates in the United States and Canada. Moreover, in all but one trajectory group, smoking prevalence consistently increased over time, suggesting these rates may continue to rise into adulthood. The longitudinal mixture modeling approach used in this study shows that smoking patterns are heterogeneous, and implications for public health policy likely vary across these diverse patterns characterized by timing of onset of use, escalation in frequency of use, and stability/change over time.
Chronic Pulmonary Histoplasmosis—A Scoping Literature Review
Authors: Baker Jacob , Kosmidis Chris , Rozaliyani Anna , Wahyuningsih Retno , Denning David W
Published: April 2020

Chronic pulmonary histoplasmosis (CPH) is an uncommon manifestation of Histoplasma infection with features similar to pulmonary tuberculosis (TB). In endemic areas, it may be misdiagnosed as smear-negative pulmonary TB. Historical case series mainly from patients with presumed TB described a high frequency of cavitation and poor prognosis, likely resulting from delayed presentation. More recent reports suggest that CPH can present with nodules, lymphadenopathy, or infiltrates, with cavities being a less common feature. Emphysema is the main risk factor for cavitary CPH. CPH is therefore an umbrella term, with chronic cavitary pulmonary histoplasmosis and Histoplasma nodules being the main long-term manifestations in nonimmunocompromised individuals. Diagnosis relies on a high index of suspicion, use of fungal culture of respiratory samples, antibody testing, and compatible radiological picture. Treatment with itraconazole for at least 12 months is recommended. Morbidity from CPH results from slow progression of cavities and gradual loss of lung function, especially if not recognized and treated. Studies on the epidemiology of CPH are needed in order to improve understanding of the disease.
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

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

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 Information

The 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 Information

Research 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.

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

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

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.