bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Corneal Topographic Patterns in Ectatic Corneal Diseases
Authors: Shah Zalak , Singh Shwetambari , Shilpy Neha , Purohit Dipali 
Published: April 2022

SIGNIFICANCE
The article highlights various topographic patterns and their prevalence in a large spectrum of ectatic corneal diseases (ECDs). Knowledge of these patterns can help clinicians for quicker diagnosis and selection of appropriate contact lens design.

PURPOSE
This study aimed to determine various corneal topography patterns and their prevalence in patients with ECDs who visited a tertiary eye hospital in western India.

METHODS
Keratoconus, pellucid marginal degeneration, keratoglobus, and post–refractive surgery progressive corneal ectasia are considered under ECDs. This cross-sectional retrospective study reviewed records of 632 consecutive patients with clinical ECDs at their first presentation. The right eye was considered for pattern analysis. In cases with suspected or forme fruste ectasia in the right eye, the fellow eye was considered. A sagittal map with standard scale of Atlas 9000 topographer (Carl Zeiss Meditec AG, Jena, Germany) was used for pattern analysis. They were classified into 18 categories and grouped under five groups. The prevalence of these patterns was calculated and assessed with 95% confidence interval (CI).

RESULTS
The mean ± SD age of patients was 23.6 ± 8.2 years. The highest prevalence was of asymmetric patterns (39.6% [95% CI, 35.7 to 43.5%]; asymmetric bowtie [AB] with steepest radial axis index [SRAX], 18.8%; AB with inferior steep, 16.0%; AB with superior steep [SS], 3.2%; symmetric bowtie with SRAX, 1.6%) and of central or paracentral patterns (28.6% [95% CI, 25.1 to 32.3%]; inferior steep, 12.2%; heart, 7.4%; oval, 4.1%; symmetric bowtie, 2.4%; round, 1.6%; irregular, 0.9%) followed by advanced patterns (17.3% [95% CI, 14.4 to 20.4%; nonmeasurable, 5.4%; globus, 4.9%; indiscriminate, 7.0%). The peripheral patterns were 11.7% (95% CI, 9.3 to 14.4%) (claw, 6.3%; junctional, 3.2%; butterfly, 1.9%; SS, 0.3%). Rare patterns were 2.8% (95% CI, 1.7 to 4.5%) (superior [junctional, claw, and heart], AB with SS with SRAX, and AB with SRAX located temporally).

CONCLUSIONS
Asymmetric and central or paracentral are the most common patterns in our study. The higher prevalence of advanced patterns indicates the need for earlier diagnosis of ECDs in our population. The peripheral patterns also have significant prevalence.
The Sun Is Still Shining: Nature of Industry Payments to Transplant Surgeons From 2014 to 2019
Authors: Lombardi Conner V. , Lang Jacob J. , Clayton Deklin , Sindhwani Puneet , Rees Michael , Ekwenna Obi 
Published: April 2022

Background.
Established in 2013, the Open Payments Program (OPP) mandated that medical device and pharmaceutical manufacturers submit record of any financial incentive given to physicians to the Centers for Medicare and Medicaid Services, which is in turn made publicly available. This study aims to characterize these payments to transplant surgeons over the first 6 y of OPP data.

Methods.
The study sample included all physicians who received at least one nonresearch payment as transplant surgeons to the OPP. To capture transplant surgeons who may be listed under their pipeline specialty, the American Society of Transplant Surgeons member directory as of January 2021 was queried. Payments were analyzed temporally, geographically, and by payment type, physician, and industry payer.

Results.
In total, payments totaling $15 661 536 were made to 1335 transplant surgeons over the study period. The mean payment was $436.90 (SD, $1760), and the median payment was $52.94 (interquartile range, $18.29–$159.80). The top contributing companies were Intuitive Surgical, Inc.; Gilead Sciences, Inc.; and Novartis Pharmaceuticals. Only 5.3% ($827 236) was paid toward faculty or as a speaker for a nonaccredited and noncertified continuing education program and honorarium. Educational payments came in at $1 233 141 (7.9%) over the study period. $13 750 828.60 (87.8%) of the payments were for other categories (consulting fees, food and beverages, etc). Organ transplant and procurement region 7 and 8 transplant surgeons received the highest median payments during the study period.

Conclusions.
This study is the first to characterize the payments made to transplant surgeons since the passage of the Sunshine Act. Further studies are needed to understand and interpret the relationship between industry and transplant surgeons, as the payments may or may not translate to influence in medical decisions or use of medical devices.
Methadone overdoses increased 48% during the COVID-19 epidemic
Authors: Kaufman Daniel E. , Kennalley Amy L. , McCall Kenneth L , Piper Brian J. 
Published: April 2022

AbstractBackgroundThe United States (US) is in the middle of an opioid overdose epidemic that has spanned over two decades and continues to escalate. Methadone is long-acting full opioid agonist which has been approved to treat opioid use disorder (OUD). Methadone can cause respiratory depression that may result in mortality. The restrictions on methadone availability including take-home dosing were loosened during the COVID-19 pandemic although there have been concerns about the high street value of diverted methadone. This report examined how fatal overdoses involving methadone have changed over the past two-decades including during the pandemic.MethodsThe Center for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (WONDER) database, which draws data from death certificates, was used to find the unintentional methadone related overdose death rate from 1999-2020. Unintentional methadone deaths were defined using the International Statistical Classification of Diseases (ICD), 10th revision codes: X40-44 with only data which was coded for methadone (T40.3). Data from the Automation of Reports and Consolidated Orders System (ARCOS) on methadone overall use, narcotic treatment programs use, and pain management use was gathered for all states, including the District of Columbia, for 2020 and corrected for population.ResultsThere have been dynamic changes over the past two-decades in overdoses involving methadone. Overdoses increased from 1999 (0.9/million) to 2007 (15.9) and declined until 2019 (6.5). Overdoses in 2020 (9.6) were 48.1% higher than in 2019 (t(50) = 3.05, p < .005).The correlations between overall methadone use (r(49) = +0.75, p < 0.001), and narcotic treatment program use (r(49) = +0.77, p < 0.001) were positive, strong, and statistically significant. However, methadone use for pain treatment was not associated with overdoses (r(49) = -.08, p = .57).ConclusionsOverdoses involving methadone significantly increased by 48.1% in 2020 relative to 2019. This mortality increase is much larger than the 5.3% elevation in calls involving methadone reported to poison control centers in the year following the March 16, 2020 loosening of methadone take-home regulations. Policy changes that were implemented following the COVID-19 pandemic involving methadone may warrant reconsideration.
Air pollution exposure and mitochondrial DNA copy number in the UK Biobank
Authors: Hong Yun Soo , Battle Stephanie L. , Puiu Daniela , Shi Wen , Pankratz Nathan , Zhao Di , Arking Dan E. , Guallar Eliseo 
Published: April 2022

ABSTRACTBackgroundLow levels of mitochondrial DNA copy number (mtDNA-CN) are a biomarker of mitochondrial dysfunction often induced by oxidative stress. Air pollution is a pervasive source of oxidative stress, but the association between air pollution exposure and mtDNA-CN is inconclusive.ObjectiveWe evaluated the association between long-term exposure to PM ≤ 10 µm diameter (PM10) and nitrogen dioxide (NO2) with mtDNA-CN in 195,196 adults in the UK Biobank study.MethodsAnnual average PM10 and NO2 concentrations were estimated using separate land-use regression models for years 2007 and 2010. mtDNA-CN was measured in blood samples collected between 2007 and 2010 and was calculated as the ratio of mitochondrial coverage to the nuclear genome coverage derived from whole-genome sequencing in 195,196 UK Biobank participants. We used standardized values (Z-scores) after log-transformation as the mtDNA-CN metric.ResultsThe median (interquartile range) annual average concentrations of PM10 and NO2 were 21.8 (20.3–23.6) and 28.9 (23.7–35.1) µg/m3 in 2007, and 16.2 (15.5–17.1) and 27.8 (22.7–32.4) µg/m3 in 2010. An increase of 10 µg/m3 in annual average PM10 and NO2 exposure was associated with an adjusted difference in mtDNA-CN of −0.089 (95% confidence interval; −0.090, −0.087) and −0.018 (−0.018, −0.017), respectively. The associations persisted for lags of up to 3 years. PM2.5-10 was also inversely associated with mtDNA-CN.ConclusionsIn this large-scale study, long-term exposure to PM10 and NO2 were inversely associated with mtDNA-CN. These findings suggest that oxidative stress-induced mitochondrial dysfunction, reflected by reduced mtDNA-CN, may be an additional mechanism mediating the health effects of air pollution.
BCG vaccination of Diversity Outbred mice induces cross-reactive antibodies to SARS-CoV-2 spike protein
Authors: Specht Aubrey G. , Kurtz Sherry L. , Elkins Karen L. , Specht Harrison , Beamer Gillian 
Published: April 2022

AbstractThe Bacillus Calmette-Guérin (BCG) vaccine, the only vaccine against tuberculosis, induces cross-protection against pathogens unrelated to Mycobacterium, including viruses. Epidemiological studies have identified potential benefits of BCG vaccination against SARS-CoV-2 infection. While BCG’s heterologous effects have been widely attributable to trained immunity, we hypothesized BCG vaccination could induce cross-reactive antibodies against the spike protein of SARS-CoV-2 Wuhan-Hu-1. The concentration of IgG reactive to SARS-CoV-2 spike protein from the sera of BCG-vaccinated, Diversity Outbred (DO) mice and C57BL/6J inbred mice was measured using ELISA. Sera from 10/15 BCG-vaccinated DO mice possessed more IgG reactive to recombinant spike protein than sera from BCG-vaccinated C57BL/6J mice and unvaccinated DO mice. Amino acid sequences common to BCG cell wall/membrane proteins and SARS-CoV-2 spike protein were identified as potential antigen candidates for future study. These results imply a humoral mechanism, influenced by genotype, by which BCG vaccination could confer immunity to SARS-CoV-2.Graphic Abstract
Biofilms preserve the transmissibility of a multi-drug resistance plasmid
Authors: Metzger Genevieve A. , Ridenhour Benjamin J. , France Michael , Gliniewicz Karol , Millstein Jack , Settles Matthew L. , Forney Larry J. , Stalder Thibault , Top Eva M. 
Published: April 2022

ABSTRACTSelf-transmissible multidrug resistance (MDR) plasmids are a major health concern because they can spread antibiotic resistance to pathogens. Even though most pathogens form biofilms, little is known about how MDR plasmids persist and evolve in biofilms. We hypothesize that (i) biofilms act as refugia of MDR plasmids by retaining them in the absence of antibiotics longer than well-mixed planktonic populations, and that (ii) the evolutionary trajectories that account for the improvement of plasmid persistence over time differ between biofilms and planktonic populations. In this study, we evolvedAcinetobacter baumanniiwith an MDR plasmid in biofilm and planktonic populations with and without antibiotic selection. In the absence of selection biofilm populations were better able to maintain the MDR plasmid than planktonic populations. In planktonic populations plasmid persistence improved rapidly but was accompanied by a loss of genes required for the horizonal transfer of plasmids. In contrast, in biofilms most plasmids retained their transfer genes, but on average plasmid persistence improved less over time. Our results showed that biofilms can act as refugia of MDR plasmids and favor the horizontal mode of plasmid transfer, which has important implications for the spread of MDR.
Change in prey genotype frequency rescues predator from extinction
Authors: Hermann Ruben Joseph , Becks Lutz 
Published: April 2022

AbstractIndirect evolutionary rescue (IER) is a mechanism where a non-evolving population is saved from extinction in an otherwise lethal environment by evolution in an interacting population. This process has been described in a predator-prey model, where extinction of the predator is prevented by a shift in the frequency of defended towards undefended prey when reduced predator densities lower selection for defended prey. We test here how increased mortality and the initial frequencies of the prey types affect IER. Combining the analysis of model simulations and experiments with rotifers feeding on an algal population we show IER in the presence of increased predator mortality. We found that IER was dependent on the ability of the prey population to evolve as well as on the frequency of the defended prey. High initial frequencies of defended prey resulted in predator extinction despite the possibility for prey evolution, as the increase in undefended prey was delayed too much to allow predator rescue. This frequency dependency for IER was more pronounced for higher predator mortalities. Our findings can help informing the development of conservation and management strategies that consider evolutionary responses in communities to environmental changes.
Autophagy modulates apical growth and development in the moss Physcomitrium patens
Authors: Pettinari Georgina , Finello Juan , Rojas Macarena Plaza , Liberatore Franco , Robert Germán , Otaiza-González Santiago , Velez Pilar , Theumer Martin , Agudelo-Romero Patricia , Gonzalez Claudio , Lascano Ramiro , Saavedra Laura 
Published: April 2022

ABSTRACTDifferent to root hairs and pollen tubes, Physcomitrium patens apical growing protonemal cells have the singularity that they continue to undergo cell divisions as the plant develops, allowing to study autophagy in the context of a multicellular apical growing tissue coupled to development. Herein, we showed that the core autophagy machinery is present in the moss P. patens, and deeply characterized the growth and development of wild-type, atg5 and atg7 loss-of-function mutants under optimal and nutrient-deprived conditions. Our results showed that the growth of the different morphological and functional protonemata apical growing cells, chloronema and caulonema, is differentially modulated by this process. These differences depend on the protonema cell type and position along the protonemal filament, and growth condition. As a global plant response, the absence of autophagy triggers the spread of the colony through protonemata growth at the expense of a reduction in buds and gametophore development, and thus the adult gametophytic and reproductive phases. Altogether this study provides valuable information indicating that autophagy has roles during apical growth with differential responses within the cell types of the same tissue and contributes to life cycle progression and thus the development of the 2D and 3D tissues of P. patens.HIGHLIGHTAutophagy is differentially induced in protonemal cells, and contributes to apical growth, life cycle progression, and thus the development of the 2D and 3D tissues of P. patens.
Modular safe-harbor transgene insertion (MosTI) for targeted single-copy and extrachromosomal array integration in C. elegans
Authors: Mouridi Sonia El , Alkhaldi Faisal , Frøkjær-Jensen Christian 
Published: April 2022

AbstractEfficient and reproducible transgenesis facilitates and accelerates research using genetic model organisms. Here we describe a modular safe harbor transgene insertion (MosTI) for use in C. elegans which improves targeted insertion of single-copy transgenes by homology directed repair and targeted integration of extrachromosomal arrays by non-homologous end-joining. MosTI allows easy conversion between selection markers at insertion site and a collection of universal targeting vectors with commonly used promoters and fluorophores. Insertions are targeted at three permissive safe-harbor intergenic locations and transgenes are reproducibly expressed in somatic and germ cells. Chromosomal integration is mediated by CRISPR/Cas9, and positive selection is based on a set of split markers (unc-119, hygroR, and gfp) where only animals with chromosomal insertions are rescued, resistant to antibiotics, or fluorescent, respectively. Single-copy insertion is efficient using either constitutive or heat-shock inducible Cas9 expression (25 - 75%) and insertions can be generated from a multiplexed injection mix. Extrachromosomal array integration is also efficient (7 - 44%) at MosTI landing sites or at the endogenous unc-119 locus. We use short-read sequencing to estimate the plasmid copy numbers for eight integrated arrays (6 to 37 copies) and long-read Nanopore sequencing to determine the structure and size (5.4 Mb) of one array. Using universal targeting vectors, standardized insertion strains, and optimized protocols, it is possible to construct complex transgenic strains which should facilitate the study of increasingly complex biological problems in C. elegans.
Development of transformation for genome editing of an emerging model organism
Authors: Yamamoto Yutaka , Gerbi Susan A. 
Published: April 2022

AbstractWith the advances in genomic sequencing, many organisms with novel biological properties are ripe for use as emerging model organisms. However, to make full use of them, transformation methods need to be developed to permit genome editing. Here, we present development of transformation for the fungus flySciara (Bradysia) coprophila; this may serve as a paradigm for development of transformation for other emerging systems, especially insects.Sciarahas a variety of unique biological features including locus-specific developmentally-regulated DNA amplification; chromosome imprinting; a monopolar spindle in male meiosis I; non-disjunction of the X chromosome in male meiosis II; X chromosome elimination in early embryogenesis; germ line limited (L) chromosomes; high resistance to radiation. Mining the unique biology ofSciararequires a transformation system to test mutations of DNA sequences that may play roles for these features. We describe aSciaratransformation system using a modified piggyBac transformation vector and detailed protocols we have developed to accommodateSciara-specific requirements. This advance will provide a platform for us and others in the growingSciaracommunity to take advantage of this unique biological system. In addition, the versatile piggyBac vectors described here and transformation methods will be useful for other emerging model systems.Author BiographiesSusan A. Gerbi(Ph.D. with Joseph Gall at Yale University 1970) is the George Eggleston, Professor of Biochemistry at Brown University. Her research includes chromosomes, DNA replication and ribosomal RNA. She was President and is a Fellow of ASCB, a Fellow of AAAS and received the RI Governor’s Award for Scientific Achievement. Other honors include RNA Society/CSHL Press Distinguished Research Mentor award; GSA George Beadle award; ASCB Senior Leadership/ Mentoring Award. She is a national leader in graduate education, including member of the National Academy of Sciences Panel on Bridges to Independence that led to the NIH K99 program, Chair of the AAMC Graduate Research Education Training Group; Chair of the FASEB Consensus Conference on Graduate Education.Yutaka Yamamoto(M.D. Kansai Medical University 1990; Ph.D. with Walter Gehring at Biozentrum – Basel 1995; postdoc with David Glover at Dundee University and University of Cambridge) is a research associate at Brown University.Graphical Abstract
Clearing of ribosome collisions by the ribosome quality control trigger complex RQT
Authors: Best Katharina , Ikeuchi Ken , Kater Lukas , Best Daniel , Musial Joanna , Matsuo Yoshitaka , Berninghausen Otto , Becker Thomas , Inada Toshifumi , Beckmann Roland 
Published: April 2022

AbstractAfter translational stalls, colliding eukaryotic ribosomes are cleared through dissociation into subunits by the ribosome quality control trigger complex, RQT, by an unknown mechanism. Here we show that RQT requires accessible mRNA and the presence of a neighboring ribosome. Cryo-EM of several RQT-ribosome complexes revealed the structural basis of splitting: RQT engages the 40S subunit of the lead ribosome and can switch between two conformations. We propose a mechanistic model in which the Slh1 helicase subunit of RQT applies a pulling force on the mRNA, causing destabilizing conformational changes of the 40S subunit. The collided ribosome functions as a ram or giant wedge, ultimately resulting in subunit dissociation. Our findings provide a first conceptual framework for a helicase driven ribosomal splitting mechanism.One-Sentence SummaryRQT clears collided ribosomes by pulling mRNA to trigger destabilizing conformational transitions for subunit dissociation.
Cystin is required for maintaining fibrocystin (FPC) levels and safeguarding proteome integrity in mouse renal epithelial cells A mechanistic connection between the kidney defects incpkmice and human ARPKD
Authors: Zhang Yiming , Yang Chaozhe , Wang Wei , Harafuji Naoe , Stasiak Piotr , Bell P. Darwin , Caldovic Ljuba , Sztul Elizabeth , Guay-Woodford Lisa M. , Bebok Zsuzsanna 
Published: April 2022

ABSTRACTAutosomal recessive polycystic kidney disease (ARPKD) is caused primarily by mutations inPKHD1, encoding fibrocystin (FPC), butPkhd1mutant mice fail to express renal cystic disease. In contrast, the renal lesion inCys1cpk/cpk(cpk) mice with loss of the cystin protein, closely phenocopy ARPKD. Recent identification of patients withCYS1-related ARPKD prompted the investigations described herein. We analyzed cystin and FPC expression in mouse models (cpk, rescued-cpk(r-cpk),Pkhd1mutants) and cortical collecting duct (CCD) cell lines (wild type (wt), cpk). We found that cystin deficiency led to diminished FPC in bothcpkkidneys and CCD cells. Inr-cpkkidneys, FPC increased and siRNA ofCys1inwtCCD cells reduced FPC. Conversely, FPC deficiency inPkhd1mutants did not affect cystin levels. Cystin deficiency and the associated reduction in FPC levels impacted the architecture of the primary cilium, but not ciliogenesis. SimilarPkhd1mRNA levels inwt, cpkkidneys and CCD cells suggested posttranslational mechanisms directed FPC loss and studies of cellular protein degradation systems revealed selective autophagy as a possible mechanism. Loss of FPC from the NEDD4 E3 ubiquitin ligase complexes caused reduced polyubiquitination and elevated levels of functional epithelial sodium channel (NEDD4 target) incpkcells. We propose that cystin is necessary to stabilize FPC and loss of cystin leads to rapid FPC degradation. FPC removal from E3-ligase complexes alters the cellular proteome and may contribute to cystogenesis through multiple mechanisms, that include MYC transcriptional regulation.