bluuebunny/crossref_metadata_2025 huggingface dataset:
Population structure and connectivity in the genusMolvain the Northeast Atlantic
Authors: McGill L , McDevitt A D , Hellemans B , Neat F , Knutsen H , Mariani S , Christiansen H , Johansen T , Volckaert F A M , Coscia I
Published: March 2023

In fisheries, operational management units and biological data often do not coincide. In many cases, this is not even known due to the lack of information about a species’ population structure or behaviour. This study focuses on two such species, the common ling Molva molva and the blue ling M. dypterygia, two Northeast Atlantic gadoids with overlapping geographical distribution, but different depth habitats. Heavily exploited throughout their ranges, with declining catches, little is known about their population structure. Genotyping-by-sequencing at thousands of genetic markers indicated that both species are separated into two major groups, one represented by samples from the coasts of western Scotland, Greenland, and the Bay of Biscay and the other off the coast of Norway. This signal is stronger for the deeper dwelling blue ling, even though adult dispersal was also identified for this species. Despite small sample sizes, fine-scale patterns of genetic structure were identified along Norway for common ling. Signatures of adaptation in blue ling consisted in signs of selections in genes involved in vision, growth, and adaptation to cold temperatures.
The Evolution of Assessing Central Nervous System Complications in Human Immunodeficiency Virus: Where Do We Go From Here?
Authors: McIntosh Roger C , Clark Uraina S , Cherner Mariana , Cysique Lucette A , Heaton Robert K , Levin Jules , Remien Robert H , Thames April , Moore David J , Rubin Leah H
Published: March 2023

In this fifth decade of the human immunodeficiency virus (HIV) epidemic, central nervous system (CNS) complications including cognitive impairment and mental health remain a burden for people with HIV (PWH) on antiretroviral therapy. Despite the persistence of these complications, which often co-occur, the underlying pathophysiology remains elusive and consequently treatments remain limited. To continue to grow our understanding of the underlying mechanisms of CNS complications among PWH, there is a need to reexamine our current approaches, which are now more than 2 decades old. At the 2021 National Institutes of Health–sponsored meeting on Biotypes of CNS Complications in PWH, the Neurobehavioral Working Group addressed the following: (1) challenges inherent to determining CNS complications; (2) heterogeneity in CNS complications; and (3) problems and solutions for examining integrated biotypes. The review below provides a summary of the main points presented and discussed by the Neurobehavioral Working Group at the meeting.
Regulation of lignocellulose degradation in microorganisms
Authors: Gurovic María Soledad Vela , Viceconte Fatima Regina , Bidegain Maximiliano Andres , Dietrich Julián
Published: March 2023

Microbial strategies for biomass deconstruction involve an incredible repertoire of enzymatic, structural, and regulatory proteins. From carbohydrate active enzymes to cellulosomes, bacteria, yeast, and filamentous fungi adapt their functional machinery to grow from alternative carbon sources such as lignocellulose and survive starvation. In that context, microbes must be able to sense, bind, degrade, and utilize lignin, cellulose, and hemicelluloses. Nature has developed specialized protein modules, RNA structures, and regulatory systems operating at a genomic, transcription, and translation level. This review briefly summarizes the main regulatory pathways involved in lignocellulose microbial degradation, including carbon catabolite repression; anti-sigma factors; regulatory RNA elements such as small RNAs, antisense RNA, RNA-binding proteins, and selective RNA processing and stabilization; and transcriptional regulators and unfolded protein response. Interplay with global regulators controlling pH response and nitrogen utilization is also revised.
Effects of low-energy diet supplemented with betaine on growth performance, nutrient digestibility, and serum metabolomic profiles in growing pigs
Authors: Fu Runqi , Liang Chan , Chen Daiwen , Tian Gang , Zheng Ping , He Jun , Yu Jie , Mao Xiangbing , Gu Zhemin , Yang Wenwu , Yu Bing
Published: March 2023

Two experiments were carried out to evaluate the effects of betaine (BET) supplementation in diets with reduced net energy (NE) levels on growth performance, nutrient digestibility, and serum metabolomic profiles in growing pigs. In experiment 1, 24 growing pigs (initial body weight, BW, 30.83 ± 2.50 kg) were allotted to one of the four treatments (six replications with 1 pig per pen) in a 2 × 2 factorial arrangement, including two dietary NE levels (2475 [N-NE] or 2395 [R80-NE] kcal/kg) and two BET doses (0 or 1500 mg/kg). In experiment 2, 72 growing pigs were used in a 2 × 3 factorial arrangement, including three dietary NE levels (2475 [N-NE], 2415 [R60-NE], or 2355 [R120-NE] kcal/kg) and two BET doses (0 or 1500 mg/kg). Pigs with initial BW of 31.44 ± 1.65 kg were divided to one of the six treatments (six replications with 2 pigs per pen). In experiment 1, lowing NE concentrations increased average daily feed intake (ADFI) by 10.69% in pigs fed the diet without BET (P > 0.05). BET significantly increased ADFI in N-NE diet (P < 0.05) but had no influence on ADFI in R80-NE diet (P > 0.05). BET enhanced the apparent digestibility of crude protein (CP), dry matter (DM), organic matter (OM), gross energy (GE), and ether extract (EE) in R80-NE diet (P < 0.05). In experiment 2, lowing NE concentrations enhanced ADFI (P > 0.05) and decreased average daily gain (ADG; P < 0.05). The reduction in feed intake by BET was further enhanced as NE concentrations decreased from 2415 to 2355 kcal/kg (P < 0.10). BET reversed the elevation of serum triglyceride, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels caused by R120-NE diet (P < 0.05). The concentrations of cholecystokinin and glucagon-like peptide 1 were increased by BET in pigs fed the R120-NE diet (P < 0.05). Serum metabolomics reveals that lowing dietary NE concentrations affected mainly amino acid biosynthetic pathways (P < 0.05). BET supplementation in R120-NE diet up-regulated serum BET levels and down-regulated homocysteine, DL-carnitine, and four amino acid secondary metabolites (P < 0.05). In conclusion, lowing dietary NE contents reduced the growth performance and caused metabolic abnormalities in growing pigs. However, BET decreased feed intake to a certain extent and improved the metabolic health of pigs fed the low-NE diets, which may be related to the dual regulation of amino acid metabolism and the secretion of appetite related hormones by BET.
Traction-related complications in hip arthroscopy for 26 years. A systematic review
Authors: Arriaza Carlos R , Navarrete Carlos Andrés , Palos Jaime , Suarez-Ahedo Carlos
Published: March 2023

The primary aim of the study is to determine the rate of traction-related complications in hip arthroscopy (HA) including perineal compression and distraction injuries, and the secondary objective is to report the incidence of complications in HA found on the studies selected by a systematic review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for data extraction from the PubMed and Cochrane databases obtained in February 2022. Reviewers extracted the title, author, date of publication, number of hips treated and number of complications describing the affected area, nerve and soft tissue injury related to traction. Studies on postless HA and HA combined with other procedures were excluded. Twenty-six years of HA literature was found in the search that included 35 studies and 8126 hips (89% Level IV) that reported the complications found during the procedure and described complications related to traction. A total of 623 hips (7.7%) had some sort of complications during HA, and complications related to traction were in 227 hips (36%). Injuries caused specifically by the perineal compression were in 144 hips (23%) that included the pudendal nerve and soft tissue injury of the groin area. Complications caused by the distraction were in 83 hips (13%) that included sciatic and peroneal nerve injury, numbness or pain of ankle and foot. HA complications occurred in 7.7% of hips treated, which is found in this systematic review. One-third of the complications are related to traction, 23% are caused by perineal compression and 13% are caused by distraction.
Monoclonal Antibodies for COVID-19 in Children: Case Series Should be Just the Start
Authors: Teoh Zheyi , Willis Zachary I
Published: March 2023

Two new articles describe the use and implementation of monoclonal antibodies to treat COVID-19 in children. While these studies provide valuable guidance for pediatric clinicians, more studies of monoclonal antibodies and other COVID-19 therapies in children are needed.
Marsupialization and peripheral ostectomy for the management of large odontogenic keratocyst: a case report
Authors: Khalil Ali , Albash Ziad , Sleman Nadim , Sayegh Wadie
Published: March 2023

Odontogenic keratocyst has been of particular interest due to its distinctive behavior and its tendency to frequently recurrence and the diversity of treatment methods. Researchers have differed over the past decades about the nature of this lesion, sometimes it was classified as a cyst and sometimes it was classified as a tumor because of its specific histopathologic features, high recurrence rate and aggressive behavior. We discuss a case of a large odontogenic keratocyst (OKC) that was treated by marsupialization followed by peripheral ostectomy. Based on our findings, we conclude that the marsupialization followed by peripheral ostectomy was a conservative and effective option for the management of large OKC.
Assessing the spin–orbit obliquity of low-mass planets in the breaking the chain formation model: a story of misalignment
Authors: Esteves Leandro , Izidoro André , Winter Othon C , Bitsch Bertram , Isella Andrea
Published: March 2023

The spin–orbit obliquity of a planetary system constraints its formation history. A large obliquity may either indicate a primordial misalignment between the star and its gaseous disc or reflect the effect of different mechanisms tilting planetary systems after formation. Observations and statistical analysis suggest that system of planets with sizes between 1 and 4 R⊕ has a wide range of obliquities (∼0–30○), and that single- and multiplanet transiting have statistically indistinguishable obliquity distributions. Here, we revisit the ‘breaking the chains’ formation model with focus in understanding the origin of spin–orbit obliquities. This model suggests that super-Earths and mini-Neptunes migrate close to their host stars via planet–disc gravitational interactions, forming chain of planets locked in mean-motion resonances. After gas-disc dispersal, about 90–99  per cent of these planetary systems experience dynamical instabilities, which spread the systems out. Using synthetic transit observations, we show that if planets are born in discs where the disc angular momentum is virtually aligned with the star’s rotation spin, their final obliquity distributions peak at ∼5° or less, and the obliquity distributions of single- and multiplanet transiting systems are statistically distinct. By treating the star-disc alignment as a free-parameter, we show that the obliquity distributions of single- and multiplanet transiting systems only become statistically indistinguishable if planets are assumed to form in primordially misaligned natal discs with a tilt’ distribution peaking at ≳10–20°. We discuss the origin of these misalignments in the context of star formation and potential implications of this scenario for formation models.
The connection between stellar mass, age, and quenching time-scale in massive quiescent galaxies atz≃ 1
Authors: Hamadouche M L , Carnall A C , McLure R J , Dunlop J S , Begley R , Cullen F , McLeod D J , Donnan C T , Stanton T M
Published: March 2023

We present a spectrophotometric study of a mass-complete sample of quiescent galaxies at 1.0 < z < 1.3 with $\mathrm{log_{10}}(M_{\star }/\mathrm{{\rm M}_{\odot }}) \ge 10.3$ drawn from the VANDELS survey, exploring the relationship between stellar mass, age, and star-formation history. Within our sample of 114 galaxies, we derive a stellar–mass versus stellar–age relation with a slope of $1.20^{+0.28}_{-0.27}$ Gyr per decade in stellar mass. When combined with recent literature results, we find evidence that the slope of this relation remains consistent over the redshift interval 0 < z < 4. The galaxies within the VANDELS quiescent sample display a wide range of star-formation histories, with a mean quenching time-scale of 1.4 ± 0.1 Gyr. We also find a large scatter in the quenching time-scales of the VANDELS quiescent galaxies, in agreement with previous evidence that galaxies at z ∼ 1 cease star formation via multiple mechanisms. We then focus on the oldest galaxies in our sample, finding that the number density of galaxies that quenched before z = 3 with stellar masses $\mathrm{log_{10}}(M_{\star }/\mathrm{{\rm M}_{\odot }}) \ge 10.6$ is $1.12_{-0.72}^{+1.47} \times 10^{-5} \ \mathrm{Mpc}^{-3}$. Although uncertain, this estimate is in good agreement with the latest observational results at 3 < z < 4, tentatively suggesting that neither rejuvenation nor merger events are playing a major role in the evolution of the oldest massive quiescent galaxies within the redshift interval 1 < z < 3.
Spatially resolved observations of outflows in the radio loud AGN of UGC 8782
Authors: Riffel Rogemar A , Riffel Rogério , Bianchin Marina , Storchi-Bergmann Thaisa , Souza-Oliveira Gabriel Luan , Zakamska Nadia L
Published: March 2023

We use optical integral field spectroscopy (IFU) to study the gas emission structure and kinematics in the inner 3.4 × 4.9 kpc2 region of the galaxy UGC 8782 (3C 293), host of a radio loud active galactic nucleus (AGN). The observations were performed with the Gemini-North multi-object spectrograph (GMOS)-IFU on the Gemini North telescope, resulting in a spatial resolution of ∼725 pc at the distance of the galaxy. While the stars present ordered rotation following the orientation of the large-scale disc, the gas shows a disturbed kinematics. The emission-line profiles present two kinematic components: a narrow (σ ≲ 200 km s−1) component associated with the gas in the disc of the galaxy and a broad (σ ≳ 200 km s−1) component produced by gas outflows. Emission-line ratio diagrams indicate that the gas in the disc is excited by the AGN radiation field, while the emission of the outflow includes additional contribution of shock excitation due to the interaction of the radio jet with the environment gas. Deviations from pure rotation, of up to 30 km s−1, are observed in the disc component and likely produced by a previous merger event. The broad component is blueshifted by ∼150–500 km s−1 relative to the systemic velocity of the galaxy in all locations. We construct radial profiles of the mass outflow rate and kinetic power of the ionized gas outflows, which have the maximum values at ∼1 kpc from the nucleus with peak values of $\dot{M}_{\rm out,\Delta R} = 0.5\pm 0.1$ M⊙ yr−1 and $\dot{K}_{\rm out,\Delta R} = (6.8\pm 1.1)\times 10^{41}$ erg s−1. The kinetic coupling efficiency of these outflows are in the range of 1–3 per cent, indicating that they could be powerful enough to affect the star formation in the host galaxy as predicted by theoretical simulations.
Efficient exploration of reionization parameters for the upcoming 21 cm observations using a photon-conserving seminumerical model SCRIPT
Authors: Maity Barun , Choudhury Tirthankar Roy
Published: March 2023

One of the most promising probes to constrain the reionization history of the universe is the power spectrum of neutral hydrogen 21 cm emission fluctuations. The corresponding analyses require computationally efficient modelling of reionization, usually achieved through seminumerical simulations. We investigate the capability of one such seminumerical code, SCRIPT, to constrain the reionization parameters. Our study involves creating a mock data set corresponding to the upcoming SKA-Low, followed by a Bayesian inference method to constrain the model parameters. In particular, we explore in detail whether the inferred parameters are unbiased with respect to the inputs used for the mock and also if the inferences are insensitive to the resolution of the simulation. We find that the model is successful on both fronts. We also develop a simple template model of reionization that can mimic the complex physical processes like inhomogeneous recombinations and radiative feedback and show that it can recover the global reionization history reliably with a moderate computational cost. However, such simple models are not suitable for constraining the properties of the ionizing sources. Our results are relevant for constraining reionization using high-quality data expected in the future telescopes.
Large-Scale Identification of Known and Novel RRNPP Quorum-Sensing Systems by RRNPP_Detector Captures Novel Features of Bacterial, Plasmidic, and Viral Coevolution
Authors: Bernard Charles , Li Yanyan , Lopez Philippe , Bapteste Eric
Published: March 2023

Gram-positive Firmicutes bacteria and their mobile genetic elements (plasmids and bacteriophages) encode peptide-based quorum-sensing systems (QSSs) that orchestrate behavioral transitions as a function of population densities. In their simplest form, termed “RRNPP”, these QSSs are composed of two adjacent genes: a communication propeptide and its cognate intracellular receptor. RRNPP QSSs notably regulate social/competitive behaviors such as virulence or biofilm formation in bacteria, conjugation in plasmids, or lysogeny in temperate bacteriophages. However, the genetic diversity and the prevalence of these communication systems, together with the breadth of behaviors they control, remain largely underappreciated. To better assess the impact of density dependency on microbial community dynamics and evolution, we developed the RRNPP_detector software, which predicts known and novel RRNPP QSSs in chromosomes, plasmids, and bacteriophages of Firmicutes. Applying RRNPP_detector against available complete genomes of viruses and Firmicutes, we identified a rich repertoire of RRNPP QSSs from 11 already known subfamilies and 21 novel high-confidence candidate subfamilies distributed across a vast diversity of taxa. The analysis of high-confidence RRNPP subfamilies notably revealed 14 subfamilies shared between chromosomes/plasmids/phages, 181 plasmids and 82 phages encoding multiple communication systems, phage-encoded QSSs predicted to dynamically modulate bacterial behaviors, and 196 candidate biosynthetic gene clusters under density-dependent regulation. Overall, our work enhances the field of quorum-sensing research and reveals novel insights into the coevolution of gram-positive bacteria and their mobile genetic elements.
Rye: genetic ancestry inference at biobank scale
Authors: Conley Andrew B , Rishishwar Lavanya , Ahmad Maria , Sharma Shivam , Norris Emily T , Jordan I King , Mariño-Ramírez Leonardo
Published: March 2023

Biobank projects are generating genomic data for many thousands of individuals. Computational methods are needed to handle these massive data sets, including genetic ancestry (GA) inference tools. Current methods for GA inference do not scale to biobank-size genomic datasets. We present Rye—a new algorithm for GA inference at biobank scale. We compared the accuracy and runtime performance of Rye to the widely used RFMix, ADMIXTURE and iAdmix programs and applied it to a dataset of 488221 genome-wide variant samples from the UK Biobank. Rye infers GA based on principal component analysis of genomic variant samples from ancestral reference populations and query individuals. The algorithm's accuracy is powered by Metropolis-Hastings optimization and its speed is provided by non-negative least squares regression. Rye produces highly accurate GA estimates for three-way admixed populations—African, European and Native American—compared to RFMix and ADMIXTURE (${R}^2 = \ 0.998 - 1.00$), and shows 50× runtime improvement compared to ADMIXTURE on the UK Biobank dataset. Rye analysis of UK Biobank samples demonstrates how it can be used to infer GA at both continental and subcontinental levels. We discuss user consideration and options for the use of Rye; the program and its documentation are distributed on the GitHub repository: https://github.com/healthdisparities/rye.
Cas9 off-target binding to the promoter of bacterial genes leads to silencing and toxicity
Authors: Rostain William , Grebert Theophile , Vyhovskyi Danylo , Pizarro Paula Thiel , Tshinsele-Van Bellingen Gatwa , Cui Lun , Bikard David
Published: March 2023

Genetic tools derived from the Cas9 RNA-guided nuclease are providing essential capabilities to study and engineer bacteria. While the importance of off-target effects was noted early in Cas9’s application to mammalian cells, off-target cleavage by Cas9 in bacterial genomes is easily avoided due to their smaller size. Despite this, several studies have reported experimental setups in which Cas9 expression was toxic, even when using the catalytic dead variant of Cas9 (dCas9). Specifically, dCas9 was shown to be toxic when in complex with guide RNAs sharing specific PAM (protospacer adjacent motif)-proximal sequence motifs. Here, we demonstrate that this toxicity is caused by off-target binding of Cas9 to the promoter of essential genes, with silencing of off-target genes occurring with as little as 4 nt of identity in the PAM-proximal sequence. Screens performed in various strains of Escherichia coli and other enterobacteria show that the nature of toxic guide RNAs changes together with the evolution of sequences at off-target positions. These results highlight the potential for Cas9 to bind to hundreds of off-target positions in bacterial genomes, leading to undesired effects. This phenomenon must be considered in the design and interpretation of CRISPR–Cas experiments in bacteria.
Excessive transcription-replication conflicts are a vulnerability of BRCA1-mutant cancers
Authors: Patel Parasvi S , Algouneh Arash , Krishnan Rehna , Reynolds John J , Nixon Kevin C J , Hao Jun , Lee Jihoon , Feng Yue , Fozil Chehronai , Stanic Mia , Yerlici Talya , Su Peiran , Soares Fraser , Liedtke Elisabeth , Prive Gil , Baider Gary D , Pujana Miquel Angel , Mekhail Karim , He Housheng Hansen , Hakem Anne , Stewart Grant S , Hakem Razqallah
Published: March 2023

BRCA1 mutations are associated with increased breast and ovarian cancer risk. BRCA1-mutant tumors are high-grade, recurrent, and often become resistant to standard therapies. Herein, we performed a targeted CRISPR-Cas9 screen and identified MEPCE, a methylphosphate capping enzyme, as a synthetic lethal interactor of BRCA1. Mechanistically, we demonstrate that depletion of MEPCE in a BRCA1-deficient setting led to dysregulated RNA polymerase II (RNAPII) promoter-proximal pausing, R-loop accumulation, and replication stress, contributing to transcription-replication collisions. These collisions compromise genomic integrity resulting in loss of viability of BRCA1-deficient cells. We also extend these findings to another RNAPII-regulating factor, PAF1. This study identifies a new class of synthetic lethal partners of BRCA1 that exploit the RNAPII pausing regulation and highlight the untapped potential of transcription-replication collision-inducing factors as unique potential therapeutic targets for treating cancers associated with BRCA1 mutations.
Short tandem repeats are important contributors to silencer elements in T cells
Authors: Hussain Saadat , Sadouni Nori , van Essen Dominic , Dao Lan T M , Ferré Quentin , Charbonnier Guillaume , Torres Magali , Gallardo Frederic , Lecellier Charles-Henri , Sexton Tom , Saccani Simona , Spicuglia Salvatore
Published: March 2023

The action of cis-regulatory elements with either activation or repression functions underpins the precise regulation of gene expression during normal development and cell differentiation. Gene activation by the combined activities of promoters and distal enhancers has been extensively studied in normal and pathological contexts. In sharp contrast, gene repression by cis-acting silencers, defined as genetic elements that negatively regulate gene transcription in a position-independent fashion, is less well understood. Here, we repurpose the STARR-seq approach as a novel high-throughput reporter strategy to quantitatively assess silencer activity in mammals. We assessed silencer activity from DNase hypersensitive I sites in a mouse T cell line. Identified silencers were associated with either repressive or active chromatin marks and enriched for binding motifs of known transcriptional repressors. CRISPR-mediated genomic deletions validated the repressive function of distinct silencers involved in the repression of non-T cell genes and genes regulated during T cell differentiation. Finally, we unravel an association of silencer activity with short tandem repeats, highlighting the role of repetitive elements in silencer activity. Our results provide a general strategy for genome-wide identification and characterization of silencer elements.
A hybrid structure determination approach to investigate the druggability of the nucleocapsid protein of SARS-CoV-2
Authors: Padroni Giacomo , Bikaki Maria , Novakovic Mihajlo , Wolter Antje C , Rüdisser Simon H , Gossert Alvar D , Leitner Alexander , Allain Frederic H-T
Published: March 2023

The pandemic caused by SARS-CoV-2 has called for concerted efforts to generate new insights into the biology of betacoronaviruses to inform drug screening and development. Here, we establish a workflow to determine the RNA recognition and druggability of the nucleocapsid N-protein of SARS-CoV-2, a highly abundant protein crucial for the viral life cycle. We use a synergistic method that combines NMR spectroscopy and protein-RNA cross-linking coupled to mass spectrometry to quickly determine the RNA binding of two RNA recognition domains of the N-protein. Finally, we explore the druggability of these domains by performing an NMR fragment screening. This workflow identified small molecule chemotypes that bind to RNA binding interfaces and that have promising properties for further fragment expansion and drug development.
Cancer Demographics and Time-to-Care in Belize
Authors: Wong Wayne , Dickerson James C , Valtis Yannis K , Habet Marta , Bernard Margaret , Kelly Lorna , Lattin John , Garrity Philip , Sood Rupali , Ohanian Alec , Chege Maryanne W , Bhatt Ami S , Huang Franklin W , Yacab Ramon
Published: March 2023

Background

Belize is a middle-income Caribbean country with poorly described cancer epidemiology and no comprehensive cancer care capacity. In 2018, GO, Inc., a US-based NGO, partnered with the Ministry of Health and the national hospital in Belize City to create the first public oncology clinic in the country. Here, we report demographics from the clinic and describe time intervals to care milestones to allow for public health targeting of gaps.

Patients and Methods

Using paper charts and a mobile health platform, we performed a retrospective chart review at the Karl Heusner Memorial Hospital (KHMH) clinic from 2018 to 2022.

Results

During this time period, 465 patients with cancer presented to the clinic. Breast cancer (28%) and cervical cancer (12%) were most common. Most patients (68%) presented with stage 3 or 4 disease and were uninsured (78%) and unemployed (79%). Only 21% of patients ever started curative intent treatment. Median time from patient-reported symptoms to a biopsy or treatment was 130 and 189 days. For the most common cancer, breast, similar times were seen at 140 and 178 days. Time intervals at the clinic: <30 days from initial visit to biopsy (if not previously performed) and <30 days to starting chemotherapy.

Conclusion

This study reports the first clinic-based cancer statistics for Belize. Many patients have months between symptom onset and treatment. In this setting, the clinic has built infrastructure allowing for minimal delays in care despite an underserved population. This further affirms the need for infrastructure investment and early detection programs to improve outcomes in Belize.
Detector bandwidth and polarization switching rates: spectrophotometric observations of the Sun by the Birmingham Solar Oscillations Network
Authors: Hale S J , Chaplin W J , Davies G R , Elsworth Y P , Howe R
Published: March 2023

The Birmingham Solar Oscillations Network (BiSON) observes acoustic oscillations of the Sun. The dominant noise source is caused by fluctuations of Earth’s atmosphere, and BiSON seeks to mitigate this effect by combining multiple rapid observations in alternating polarization states. Current instrumentation uses bespoke Pockels-effect cells to select the polarization state. Here, we investigate an alternative off-the-shelf solution, a liquid crystal (LC) retarder, and discuss the potential impact of differences in performance. We show through electrical simulation of the photodiode-based detectors, and assessment of both types of polarization device, that although the switching rate is slower the off-the-shelf LC retarder is a viable replacement for a bespoke Pockels-effect cell. The simplifications arising from the use of off-the-shelf components allow easier and quicker instrumentation deployment.
Changing conceptualization of innovation in the European Union and its impact on universities: Critical junctures and evolving institutional demands
Authors: Cinar Ridvan , Benneworth Paul , Coenen Lars
Published: March 2023

This article explores underlying mechanisms triggering a change in conceptualization of innovation in the European Union (EU), the impact of this change on institutional demands upon European universities and implications for evaluation procedures. We mobilize the theoretical concept of critical junctures to explore significant periods that have affected understanding of innovation in the EU as well as institutional expectations from universities. Through an analysis of European policy corpus relating to innovation, we identify three distinct periods, 1983–6, 1995–2000, and 2008–12, entailing fairly fundamental shifts that have considerably broadened the understanding of innovation and then demonstrate the way this broadening conceptualization has affected institutional demands upon universities. Following this, we discuss the implications of the critical junctures on evaluation approaches. We conclude by arguing that different approaches towards innovation have created complex institutional environment for universities to navigate and suggest that implementing more nuanced and customized evaluation schemes aligned to the institutional demands of each critical juncture could help addressing this complexity.
Performance of the 2016 ACR-EULAR myositis response criteria in juvenile dermatomyositis therapeutic trials and consensus profiles
Authors: Kim Hanna , Saygin Didem , Douglas Christian , Wilkerson Jesse , Erman Brian , Pistorio Angela , McGrath John A , Reed Ann M , Oddis Chester V , Bracaglia Claudia , van Royen-Kerkhof Annet , Bica Blanca , Dolezalova Pavla , Ferriani Virginia P L , Flato Berit , Bernard-Medina Ana G , Herlin Troels , Miller Frederick W , Vencovsky Jiri , Ruperto Nicolino , Aggarwal Rohit , Rider Lisa G ,   for the International Myositis Assessment and Clinical Studies Group (IMACS) and Paediatric Rheumatology INternational Trials Organization (PRINTO), Pinal-Fernandez Iago , Kim Susan , Ascherman Dana , Schiffenbauer Adam
Published: March 2023

Objectives

The 2016 ACR-EULAR Response Criteria for JDM was developed as a composite measure with differential weights of six core set measures (CSMs) to calculate a Total Improvement Score (TIS). We assessed the contribution of each CSM, representation of muscle-related and patient-reported CSMs towards improvement, and frequency of CSM worsening across myositis response criteria (MRC) categories in validation of MRC.

Methods

Data from JDM patients in the Rituximab in Myositis trial (n = 48), PRINTO JDM trial (n = 139), and consensus patient profiles (n = 273) were included. Observed vs expected CSM contributions were compared using Sign test. Characteristics of MRC categories were compared by Wilcoxon tests with Bonferroni adjustment. Spearman correlation of changes in TIS and individual CSMs were examined. Agreement between physician-assessed change and MRC categories was evaluated by weighted Cohen’s kappa.

Results

Of 457 JDM patients with IMACS CSMs and 380 with PRINTO CSMs, 9–13% had minimal, 19–23% had moderate and 41–50% had major improvement. The number of improved and absolute percentage change of CSMs increased by MRC improvement level. Patients with minimal improvement by MRC had a median of 0–1 CSM worsened, and those with moderate/major improvement had a median of zero worsening CSMs. Of patients improved by MRC, 94–95% had improvement in muscle strength and 93–95% had improvement in ≥1 patient-reported CSM. IMACS and PRINTO CSMs performed similarly. Physician-rated change and MRC improvement categories had moderate-to-substantial agreement (Kappa 0.5–0.7).

Conclusion

The ACR-EULAR MRC perform consistently across multiple studies, supporting its further use as an efficacy end point in JDM trials.
NATURAL RADIOACTIVITY AND ASSESSMENT OF HAZARD INDICES OF THE SOIL FOUND AT SUNG VALLEY, MEGHALAYA
Authors: Ryngnga Jodie T , Jyrwa B M , Nandy Maitreyee , Saxena Atul
Published: March 2023

In this work, the variation of the radioactivity at different depth of the soil found at the Sung Valley in West Jaiñtia Hills District of Meghalaya in India is estimated by using the gamma-ray spectroscopy. The average activity concentration of 226Ra, 232Th and 40K for soil samples at different depths are measured to be 57, 156 and 352 Bq kg−1, respectively. The radiological hazard indices for the soil samples are calculated using standard models in order to determine the safe utility of these materials that are being used to manufacture domestic products by the locals. Values of all the radiological hazard indices are observed to be within the internationally recommended values as proposed by the European Commission and the United Nations Scientific Committee on the Effects of Atomic Radiation. The present study ensures that the soil analysed presents a negligible radiation hazard, and produced poetries and artefacts radiological incidence will stay within the allowed natural limit.
FOIL ACTIVATION TECHNIQUE—A TOOL FOR THE EVALUATION OF PHOTO-NEUTRON DOSE IN RADIOTHERAPY
Authors: Sathian Deepa , Bakshi Ashok K , Kannan Umasankari , Beck Mudit , Haneefa Abdul , Cyriac Siji
Published: March 2023

Treatment of cancer is carried out using photon beams from high-energy medical linear accelerators. Photo-neutrons are also produced as an unwanted by product in the process of dose delivery to the cancer patients during their radiation treatments. In the present study, photo-neutron dose equivalents (both thermal and fast components) per unit delivered gamma-photon dose were measured at different depths, as function of distances from iso-centre in patient plane, field sizes, wedge angles and at LINAC head for a 15-MV medical linear accelerator model Elekta Precise using multi-foil activation technique. The neutron dose equivalents determined for the above-mentioned parameters were found to be lower (<0.05%) in comparison with the therapeutic photon dose delivered and within the prescribed limits recommended by the national regulatory authority.
Race, State Surveillance, and Policy Spillover: Do Restrictive Immigration Policies Affect Citizen Earnings?
Authors: Browne Irene , An Weihua , Auguste Daniel , Delia-Deckard Natalie
Published: March 2023

This paper investigates whether restrictive immigration policy affects earnings among White, African-American, and Latinx US citizens. Incorporating sociological theories of race that point to state surveillance of Black and Latinx bodies as a linchpin of racial inequality, we ask: Do immigration policies that expand the reach of law enforcement spill over to lower or to raise earnings of employed US citizens? If so, are the effects of these policies greater for Latinx and African-American citizens compared to their White counterparts? Are the effects of these policies stronger among Latinx and African-American men—who are more directly targeted by surveillance policing as a function of their gender—than for co-ethnic women? To investigate these questions, we combine two nationally representative longitudinal datasets—the 1979 National Longitudinal Survey of Youth and the 1997 National Longitudinal Survey of Youth. We find that immigration policies that expand the reach of law enforcement raise wages among native-born Whites. However, we also find that state policies enhancing immigration law enforcement decrease wages among Latinx and African-American citizens compared to Whites. We find no gender/race interactions influencing spillover effects of immigration policy on earnings.
Evolution of semiaquatic habits in hippos and their extinct relatives: insights from the ear region
Authors: Orliac Maëva J , Mourlam Mickaël J , Boisserie Jean-Renaud , Costeur Loïc , Lihoreau Fabrice
Published: March 2023

Since molecular data identified hippopotamids as the closest living relatives of cetaceans, a common aquatic/semiaquatic ancestor hypothesis for these modern taxa has naturally been proposed. However, recent molecular studies concluded that most molecular adaptations in extant cetaceans occurred after their split from hippopotamids. If the question of aquatic affinities of the first cetaceans has been investigated at large, it has not been the case for the forebears of hippopotamids. Sensory organs are drastically affected by underwater perception. In this work, we question the aquatic affinities of fossil hippopotamoids through an investigation of the morphology and morphometrics of the petrosal bone and cochlea of 12 extinct hippopotamoid taxa. Petrosal and bony labyrinth morphological characters constitute a source of structured phylogenetic signal, both supporting major hippopotamoid clades and bringing original relationships. The morphometric study of functional measurements of the cochlear canal shows that anthracotheres bridge the morphological gap between terrestrial artiodactyls and modern hippopotamids. The integrated functional signal of the ear region further supports convergent acquisitions of semiaquatic behaviour in hippopotamids and cetaceans and indicates that terrestrial hearing was an ancestral trait among Hippopotamoidea. We highlight multiple convergent acquisitions of semiaquatic traits in the ear region of hippopotamoids and new robust phylogenetic characters.
Molecular analysis of 12 Chinese patients with 11β‐hydroxylase deficiency and in vitro functional study of 20 CYP11B1 missense variants
Authors: Sun Bang , Lu Lin , Xie Shaowei , Zhang Wei , Zhang Xiaoxia , Tong Anli , Chen Shi , Wu Xueyan , Mao Jiangfeng , Wang Xi , Qiu Ling , Nie Min
Published: March 2023

Steroid 11β‐hydroxylase deficiency (11β‐OHD) is a rare autosomal recessive disorder caused by pathogenic variants of CYP11B1 gene. This study aimed to perform molecular analysis of a Chinese 11β‐OHD series and in vitro functional study of twenty CYP11B1 missense variants. Twelve Chinese patients with clinical diagnosis of 11β‐OHD were included in the study to analyze their molecular etiology. Genomic DNA of patients was extracted to be sequenced all coding exons and intronic flanking sequences of CYP11B1. Fourteen missense variants found in 12 patients mentioned above along with 6 missense variants previously reported by our team were evaluated functionally. Amino acid substitutions were analyzed with computational program to determine their effects on the three‐dimensional structure of CYP11B1 protein. Clinical characteristics and hormone levels at baseline of the 18 patients carrying 18 missense variants aforementioned were recorded to perform genotype–phenotype correlation. A total of 21 rare variants including 9 novel and 12 recurrent ones were identified in 12 patients, out of which 17 were missense, 2 were nonsense, 1 was a splice site variant, and 1 was a deletion–insertion variant. Results of in vitro functional study revealed that 3 out of 20 missense mutants (p.Leu3Pro, p.Gly267Ser, and p.Ala367Ser) had partial enzyme activity and the other 17 had little enzymatic activity. The impairment degree of enzymatic activity in vitro functional study was also reflected in the severity degree of interaction change between the wild‐type/mutant‐type amino acid and its adjacent amino acids in three‐dimensional model. In conclusion, the addition of 9 novel variants expands the spectrum of CYP11B1 pathogenic variants. Our results demonstrate that twenty CYP11B1 variants lead to impaired 11β‐hydroxylase activity in vitro. Visualizing these variants in the three‐dimensional model structure of CYP11B1 protein can provide a plausible explanation for the results measured in vitro.
Availability of Specific Programs and Medications for Addiction Treatment to Vulnerable Populations: Results from the Addiction Treatment Locator, Assessment, and Standards (ATLAS) Survey
Authors: Oldfield Benjamin J. , Chen Kevin , Joudrey Paul J. , Biegacki Emma T. , Fiellin David A.
Published: March 2023

Objectives

This study aimed to describe addiction treatment facilities by their offerings of medications for alcohol use disorder (MAUD) and/or for opioid use disorder (MOUD), and by their offering services to groups with barriers to care: uninsured and publicly insured, youth, seniors, individuals preferring to receive care in Spanish, and sexual minority individuals.

Methods

We examined addiction treatment facility survey data in 6 US states. We performed bivariate analyses comparing facilities that offered MAUD, MOUD, and both (main outcomes). We then constructed a multivariable model to identify predictors of offering MAUD, MOUD, or both, including exposures that demonstrate programming for special populations.

Results

Among 2474 facilities, 1228 (50%) responded between October 2019 and January 2020. Programs were offered for youth (30%), elderly (40%), Spanish-speaking (37%), and sexual minority populations (39%), with 58% providing MAUD, 67% providing MOUD, and 56% providing both. Among those providing MAUD, MOUD, or both, a majority (>60% for all exposures) offered programming to vulnerable populations. With Delaware as reference, Louisiana (adjusted odds ratio [aOR], 0.28; 95% confidence interval [CI], 0.12–0.67) and North Carolina (aOR, 0.33; 95% CI, 0.15–0.72) facilities had lesser odds of offering both MAUD and MOUD. All exposures identifying facilities offering treatment to vulnerable groups were associated with offerings of MAUD and/or MOUD except for offerings to youth; these facilities had less odds of offering MOUD (aOR, 0.31; 95% CI, 0.31–0.62).

Conclusions

There are facility-level disparities in providing MAUD and MOUD by state, and facilities with youth programming have lesser odds of offering MOUD than other facilities.
Outcomes of Extremely Prolonged (> 50 d) Venovenous Extracorporeal Membrane Oxygenation Support
Authors: Malas Jad , Chen Qiudong , Shen Tao , Emerson Dominic , Gunn Tyler , Megna Dominick , Catarino Pedro , Nurok Michael , Bowdish Michael , Chikwe Joanna , Cheng Susan , Ebinger Joseph , Kumaresan Abirami
Published: March 2023

Objectives:

There has been a sustained increase in the utilization of venovenous extracorporeal membrane oxygenation (ECMO) over the last decade, further exacerbated by the COVID-19 pandemic. We set out to describe our institutional experience with extremely prolonged (> 50 d) venovenous ECMO support for recovery or bridge to lung transplant candidacy in patients with acute respiratory failure.

Design:

Retrospective cohort study.

Setting:

A large tertiary urban care center.

Patients:

Patients 18 years or older receiving venovenous ECMO support for greater than 50 days, with initial cannulation between January 2018 and January 2022.

Interventions:

None.

Measurements and Main Results:

One hundred thirty patients were placed on venovenous ECMO during the study period. Of these, 12 received prolonged (> 50 d) venovenous ECMO support. Eleven patients (92%) suffered from adult respiratory distress syndrome (ARDS) secondary to COVID-19, while one patient with prior bilateral lung transplant suffered from ARDS secondary to bacterial pneumonia. The median age of patients was 39 years (interquartile range [IQR], 35–51 yr). The median duration of venovenous ECMO support was 94 days (IQR, 70–128 d), with a maximum of 180 days. Median time from intubation to cannulation was 5 days (IQR, 2–14 d). Nine patients (75%) were successfully mobilized while on venovenous ECMO support. Successful weaning of venovenous ECMO support occurred in eight patients (67%); 6 (50%) were bridged to lung transplantation and 2 (17%) were bridged to recovery. Of those successfully weaned, seven patients (88%) were discharged from the hospital. All seven patients discharged from the hospital were alive 6 months post-decannulation; 83% (5/6) with sufficient follow-up time were alive 1-year after decannulation.

Conclusions:

Our experience suggests that extremely prolonged venovenous ECMO support to allow native lung recovery or optimization for lung transplantation may be a feasible strategy in select critically ill patients, further supporting the expanded utilization of venovenous ECMO for refractory respiratory failure.
MALIGNANT TRANSFORMATION OF A CHOROIDAL NEVUS AFTER 19 YEARS OF OBSERVATION FOLLOWED BY RAPID PROGRESSION OF THE CHOROIDAL MELANOMA
Authors: Istre-Wilz Hannah M. , Di Nicola Maura , Augsburger James J. , Williams Basil K.
Published: March 2023

Purpose:

To describe the case of a woman who developed rapid progression of a choroidal melanoma after 19 years of observation of a previously treated choroidal nevus.

Methods:

A 71-year-old woman with a 22-year history of a choroidal nevus was observed for 19 years after undergoing transpupillary thermotherapy for a localized, macula-involving, exudative, retinal detachment. Five months after her most recent stable examination, she presented for routine follow-up.

Results:

The lesion was noted to have increased thickness with the development of lipofuscin and subretinal fluid, suggestive of malignant transformation. In the 1 month between diagnosis and treatment with iodine-125 plaque brachytherapy, the lesion continued to expand, requiring a radiation dose adjustment.

Conclusion:

Choroidal nevus transformation into melanoma has been well-documented, highlighting the need for routine follow-up. Treatment within 1 month is typically sufficient for appropriate management. Occasionally, melanomas may grow substantially between diagnosis and treatment, suggesting that repeat measurement may be necessary in rare instances to ensure appropriate radiation treatment.
Characteristics of Fecal Incontinence
Authors: Hoedl Manuela , Osmancevic Selvedina , Bauer Silvia
Published: March 2023

Objectives

The aim of conducting this study was to investigate the relations between different characteristics of fecal incontinence (FI) and incontinence-associated dermatitis (IAD), placing a focus on stool consistency.

Methods

This is a secondary data analysis of data from cross-sectional studies. We merged data from the years 2014, 2015, and 2016.

Results

Of all participating persons, 1.9% were only fecal incontinent and 8.6% lost both urine and fecal material, of which 28.8% lost liquid fecal material and 71.2% lost solid stool. The prevalence of IAD among persons with FI was 5.6%. Persons with liquid FI had a 2.786-time higher risk of developing an IAD than persons with solid stool.

Conclusion

Because of the higher risk of developing an IAD, persons with liquid FI should be analyzed in further studies by applying the definition of FI from the International Continence Society and referring to the Bristol stool chart.