bluuebunny/crossref_metadata_2025_split huggingface dataset:
Likelihood-Based Tests of Species Tree Hypotheses
Authors: Adams Richard , DeGiorgio Michael 
Published: July 2023

AbstractLikelihood-based tests of phylogenetic trees are a foundation of modern systematics. Over the past decade, an enormous wealth and diversity of model-based approaches have been developed for phylogenetic inference of both gene trees and species trees. However, while many techniques exist for conducting formal likelihood-based tests of gene trees, such frameworks are comparatively underdeveloped and underutilized for testing species tree hypotheses. To date, widely used tests of tree topology are designed to assess the fit of classical models of molecular sequence data and individual gene trees and thus are not readily applicable to the problem of species tree inference. To address this issue, we derive several analogous likelihood-based approaches for testing topologies using modern species tree models and heuristic algorithms that use gene tree topologies as input for maximum likelihood estimation under the multispecies coalescent. For the purpose of comparing support for species trees, these tests leverage the statistical procedures of their original gene tree-based counterparts that have an extended history for testing phylogenetic hypotheses at a single locus. We discuss and demonstrate a number of applications, limitations, and important considerations of these tests using simulated and empirical phylogenomic data sets that include both bifurcating topologies and reticulate network models of species relationships. Finally, we introduce the open-source R package SpeciesTopoTestR (SpeciesTopology Tests in R) that includes a suite of functions for conducting formal likelihood-based tests of species topologies given a set of input gene tree topologies.
Proterozoic Acquisition of Archaeal Genes for Extracellular Electron Transfer: A Metabolic Adaptation of Aerobic Ammonia-Oxidizing Bacteria to Oxygen Limitation
Authors: Gulay Arda , Fournier Greg , Smets Barth F , Girguis Peter R 
Published: July 2023

AbstractMany aerobic microbes can utilize alternative electron acceptors under oxygen-limited conditions. In some cases, this is mediated by extracellular electron transfer (or EET), wherein electrons are transferred to extracellular oxidants such as iron oxide and manganese oxide minerals. Here, we show that an ammonia-oxidizer previously known to be strictly aerobic, Nitrosomonas communis, may have been able to utilize a poised electrode to maintain metabolic activity in anoxic conditions. The presence and activity of multiheme cytochromes in N. communis further suggest a capacity for EET. Molecular clock analysis shows that the ancestors of β-proteobacterial ammonia oxidizers appeared after Earth's atmospheric oxygenation when the oxygen levels were &gt;10−4pO2 (present atmospheric level [PAL]), consistent with aerobic origins. Equally important, phylogenetic reconciliations of gene and species trees show that the multiheme c-type EET proteins in Nitrosomonas and Nitrosospira lineages were likely acquired by gene transfer from γ-proteobacteria when the oxygen levels were between 0.1 and 1 pO2 (PAL). These results suggest that β-proteobacterial EET evolved during the Proterozoic when oxygen limitation was widespread, but oxidized minerals were abundant.
Structures of CTCF–DNA complexes including all 11 zinc fingers
Authors: Yang Jie , Horton John R , Liu Bin , Corces Victor G , Blumenthal Robert M , Zhang Xing , Cheng Xiaodong 
Published: July 2023

Abstract
The CCCTC-binding factor (CTCF) binds tens of thousands of enhancers and promoters on mammalian chromosomes by means of its 11 tandem zinc finger (ZF) DNA-binding domain. In addition to the 12–15-bp CORE sequence, some of the CTCF binding sites contain 5′ upstream and/or 3′ downstream motifs. Here, we describe two structures for overlapping portions of human CTCF, respectively, including ZF1–ZF7 and ZF3–ZF11 in complex with DNA that incorporates the CORE sequence together with either 3′ downstream or 5′ upstream motifs. Like conventional tandem ZF array proteins, ZF1–ZF7 follow the right-handed twist of the DNA, with each finger occupying and recognizing one triplet of three base pairs in the DNA major groove. ZF8 plays a unique role, acting as a spacer across the DNA minor groove and positioning ZF9–ZF11 to make cross-strand contacts with DNA. We ascribe the difference between the two subgroups of ZF1–ZF7 and ZF8–ZF11 to residues at the two positions −6 and −5 within each finger, with small residues for ZF1–ZF7 and bulkier and polar/charged residues for ZF8–ZF11. ZF8 is also uniquely rich in basic amino acids, which allows salt bridges to DNA phosphates in the minor groove. Highly specific arginine–guanine and glutamine–adenine interactions, used to recognize G:C or A:T base pairs at conventional base-interacting positions of ZFs, also apply to the cross-strand interactions adopted by ZF9–ZF11. The differences between ZF1–ZF7 and ZF8–ZF11 can be rationalized structurally and may contribute to recognition of high-affinity CTCF binding sites.
Randomized trial comparing standard versus thermocontrolled haemodialysis using intradialytic cardiac, brain and renal magnetic resonance imaging
Authors: Gullapudi Venkata R Latha , Cox Eleanor F , Buchanan Charlotte E , Canaud Bernard , White Kelly , Taal Maarten W , Selby Nicholas M , Francis Susan T 
Published: July 2023

ABSTRACT

Background
Ischaemic end-organ damage during haemodialysis (HD) is a significant problem that may be ameliorated by intradialytic cooling. A randomised trial was performed to compare standard HD (SHD; dialysate temperature 37°C) and programmed cooling of the dialysate [thermocontrolled HD (TCHD)] using multiparametric magnetic resonance imaging (MRI) to assess structural, functional and blood flow changes in the heart, brain and kidneys.

Methods
Prevalent HD patients were randomly allocated to receive either SHD or TCHD for 2 weeks before undergoing serial MRI at four time points: pre-, during (30 min and 180 min) and post-dialysis. MRI measures include cardiac index, myocardial strain, longitudinal relaxation time (T1), myocardial perfusion, internal carotid and basilar artery flow, grey matter perfusion and total kidney volume. Participants then crossed to the other modality to repeat the study protocol.

Results
Eleven participants completed the study. Separation in blood temperature between TCHD (−0.1 ± 0.3°C) and SHD (+0.3 ± 0.2°C; P = .022) was observed, although there was no difference in tympanic temperature changes between arms. There were significant intradialytic reductions in cardiac index, cardiac contractility (left ventricular strain), left carotid and basilar artery blood flow velocities, total kidney volume, longitudinal relaxation time (T1) of the renal cortex and transverse relaxation rate (T2*) of the renal cortex and medulla, but no differences between arms. Pre-dialysis T1 of the myocardium and left ventricular wall mass index were lower after 2 weeks of TCHD compared with SHD [1266 ms (interquartile range 1250–1291) versus 1311 ± 58 ms, P = .02; 66 ± 22 g/m2 versus 72 ± 23 g/m2, P = .004].

Conclusions
HD adversely affects cardiac function, reduces carotid and basilar artery blood flow and total kidney volume, but mild dialysate cooling using a biofeedback module did not result in differences in intradialytic MRI measures compared with SHD.
MULTIPLATFORM MOLECULAR ANALYSIS OF VESTIBULAR SCHWANNOMA REVEALS TWO ROBUST SUBGROUPS WITH DISTINCT MICROENVIRONMENT
Authors: Landry Alexander P , Wang Justin Z , Suppiah Suganth , Zadeh Gelareh 
Published: July 2023

Abstract
BTFC travel award recipient
Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle and poses a significant morbidity for patients. While many exhibit benign behaviour, others have a more aggressive nature and pattern of growth. Predicting who will fall into which category consistently remains uncertain. There is a need for a better understanding of the molecular landscape, and important subgroups therein, of this disease.
METHODS: We select all vestibular schwannomas from our tumour bank with both methylation and RNA profiling available. Unsupervised clustering methods were used to define two distinct molecular subgroups of VS which were explored using computational techniques including bulk deconvolution analysis, gene pathway enrichment analysis, and drug repurposing analysis. Methylation data from two other cohorts were used to validate our findings, given a paucity of external samples with available multi-omic data. RESULTS: A total of 75 tumours were analyzed. Consensus clustering and similarity network fusion defined two subgroups ("immunogenic" and "proliferative”) with significant differences in immune, stroma, and tumour cell abundance (p&lt;0.05). Gene network analysis and computational drug repurposing found critical differences in targets of immune checkpoint inhibition PD-1 and CTLA-4, the MEK pathway, and the epithelial to mesenchymal transition program, suggesting a need for subgroup-specific targeted treatment/trial design in the future. CONCLUSIONS: We leverage computational tools with multi-omic molecular data to define two robust subgroups of vestibular schwannoma with differences in microenvironment and therapeutic vulnerabilities.
A FIRST REPORT ON OUTCOMES OF STEREOTACTIC BODY RADIOTHERAPY FOR POSTERIOR ELEMENT ONLY SPINAL METASTASES AND VALIDATION OF RECOMMENDED CLINICAL TARGET VOLUME DELINEATION PRACTICE
Authors: Burgess Laura , Zeng K Liang , Myrehaug Sten , Soliman Hany , Tseng Chia-Lin , Detsky Jay , Chen Hanbo , Palhares Daniel Moore , Witiw Christopher D , Zhang Beibei , Maralani Pejman , Sahgal Arjun 
Published: July 2023

Abstract
Spine stereotactic body radiotherapy (SBRT) improves local control and pain response compared to conventional external beam radiotherapy. Consensus stipulates MRI-based delineation of the clinical target volume (CTV) and is based on spine segment sector involvement. The applicability to metastases limited to the posterior elements remains to be validated. We aimed to determine the patterns of failure and safety of treating posterior element metastases when the vertebral body (VB) was intentionally excluded from the CTV.
METHODS AND MATERIALS: A retrospective review of a prospectively maintained database of 605 patients and 1412 spine segments treated with spine SBRT was performed. Only treated segments involving the posterior elements alone were included. The primary outcome was local failure and secondary outcomes included patterns of failure, toxicities. RESULTS: 24/605 patients and 31/1412 segments were treated to the posterior elements only. Local failure occurred in 11/31 segments. The cumulative rate of local recurrence was 9.7% at 12 months and 30.8% at 24 months. Amongst local failures, the most common histologies were renal cell carcinoma (36.4%) and non-small cell lung cancer (36.4%) and 73% had baseline paraspinal disease extension. 6/11 (54.5%) failed exclusively within treated CTV sectors and 5/11 (45.5%) with both treated and adjacent untreated sectors. 4/5 cases had recurrent disease extending into the VB, but no failure was observed exclusively within the VB. CONCLUSIONS: Posterior element alone metastases are rare. Our analyses support SBRT consensus contouring guidelines such that the VB can be excluded from CTV in spinal metastases confined to the posterior elements.
BEVACIZUMAB FOR SYMPTOMATIC RADIATION NECROSIS IN BRAIN METASTASES: OUTCOMES FROM A SINGLE-CENTER RETROSPECTIVE ANALYSIS
Authors: Roberto Katrina , Tyono Ivan , Soliman Hany , Sahgal Arjun , Perry James , Lim-Fat Mary Jane 
Published: July 2023

Abstract
Radiation necrosis is a late complication after radiotherapy and can be treated with bevacizumab, however predictors of response are not well established. We performed a single-institution retrospective chart review of patients with previously irradiated brain metastases who developed radiation necrosis and were treated with bevacizumab. 19 patients (86% female, median age of 62 years) were included. 50% had metastatic lung cancer, 37% had breast cancer and 11 % had melanoma. 18 had perfusion imaging, 9 had chemical exchange saturation transfer (CEST) imaging to increase diagnostic confidence. 6 cases were tissue-confirmed, 3 before treatment, and 3 upon recurrence after bevacizumab. All patients received a dose of 7.5 mg/kg per infusion every 3 weeks and 63% received 4 infusions. All were symptomatic before treatment. Clinical response was seen in 89% while radiographic response was achieved in 95% of patients. Dexamethasone was successfully discontinued in 71% of steroid-dependent patients. The median duration of response (interval between first infusion and recurrence) was 7.2 months (range: 2.3 to 43.2). Of the nine diagnosed using perfusion and CEST imaging, 89% had clinical response, 100% had a reduction in T2/FLAIR volume and 89% in T1 post-gadolinium enhancement, 83% discontinued dexamethasone. Grade 1/2 adverse events occurred in 8 patients (hypertension, fatigue, rash, joint pain, intracranial hemorrhage). One patient developed a grade 3 bowel perforation requiring surgery. Bevacizumab resulted in significant and prolonged clinical and radiographic improvement in a series of carefully selected patients. CEST imaging helped select responders to bevacizumab in our cohort.
CEREBELLAR DIFFUSE MIDLINE GLIOMA, H3K27M ALTERED IN A FIFTY-FIVE-YEAR-OLD PATIENT
Authors: Ibdah Haleem , Pejhan Shervin , Ang Lee , Hawkins Cynthia , Fisher Barbara , Megyesi Joseph , MacDonald Maria 
Published: July 2023

Abstract
H3 K27M mutations were first identified in Pediatric Diffuse Intrinsic Pontine Glioma and are now recognized in gliomas occurring in other midline locations such as the thalamus, spinal cord and cerebellum. These gliomas were renamed to Diffuse Midline Glioma (DMG) H3 K27-altered in the 2021 WHO classification due to the discovery of alternate mechanisms of H3 K27 loss. These gliomas are more commonly found in children but also occur in adolescents and young adults. We present the case of a 55- year-old woman who presented with a 2.5-month history of nausea, vomiting and gait impairment. Imaging revealed a partially cystic, enhancing lesion in the midline of the cerebellum. She had a gross total resection with pathology revealing Diffuse Midline Glioma, H3K27 altered, subgroup DMG, H3 wildtype with EZHIP over-expression, WHO grade 4. The patient completed chemoradiation with temozolomide with plans to enroll in a clinical trial upon progression. However due to loss of ambulation and function she was admitted to hospice. The patient survived 24 months after her surgery, a period longer than the reported median overall survival in DMG with EZIP overexpression which is 16 months. This case illustrates the importance of considering DMG H3K27- altered glioma in adults older than 40 years who present with infiltrative IDH wildtype glioma in midline locations. Recognition of this diagnosis may allow enrollment in clinical trials and should prompt molecular testing for concurrent targetable alterations in the RAS-MAPK-pathway (e.g., mutations in BRAF V600E, FGFR1, NF1 and NTRK) and PI3K-mTOR pathway (e.g., PIK3CA mutation).
30 GY IN 4 STEREOTACTIC BODY RADIOTHERAPY (SBRT) FRACTIONS FOR COMPLEX SPINAL METASTASES: MATURE OUTCOMES SUPPORTING THIS NOVEL REGIMEN
Authors: Moore-Palhares Daniel , Sahgal Arjun , Liang Zeng K , Myrehaug Sten , Tseng Chia-Lin , Detsky Jay , Chen Hanbo , Ruschin Mark , Atenafu Eshetu G , Wilson Jeff , Larouche Jeremie , da Costa Leodante , Maralani Pejman Jabehdar , Soliman Hany 
Published: July 2023

Abstract
We designed a 30 Gy in 4 fractions stereotactic body radiotherapy (SBRT) protocol, as an alternative option to our standard 2-fraction approach, for primarily large volume, multilevel, or previously radiated spinal metastases. We report imaging-based outcomes of this novel fractionation scheme.
MATERIALS AND METHODS: Retrospective analysis of all patients who underwent 30 Gy/4 fractions from 2010-2021 identified from an institutional database. Primary outcomes were magnetic resonance-based vertebral compression fracture (VCF) and local failure (LF). RESULTS: We reviewed 245 treated segments in 116 patients. The median number of consecutive segments within the treatment volume was 2 (range, 1-6) and clinical target volume (CTV) was 126.2 cc (range, 10.4-863.5). Fifty-four percent had received at least one prior course of radiotherapy. The cumulative incidence of LF was 10.7% (95% CI 7.1-15.2) at 1 year and 16% (95% CI 11.5-21.2) at 2 years. The cumulative incidence of VCF was 7.3% (95% CI 4.4-11.2) at 1 and 11.2% (95% CI 7.5-15.8) at 2 years. On multivariable analysis, age ≥68 years (p=0.038), CTV volume ≥72 cc (p=0.021), and no prior surgery (p=0.021) predicted for VCF. The risk of VCF for CTV volumes &lt;72 cc/≥72 cc was 1.8%/14.6% at 2 years. No case of radiation-induced myelopathy was observed. CONCLUSION: 30 Gy in 4 fractions was safe and efficacious despite a population at increased risk of toxicity. The lower risk of VCF in previously stabilized segments highlights the potential for a multi-modal treatment approach for complex metastases, especially for those with CTV volume ≥72 cc.
What, where, and how: Regulation of translation and the translational landscape in plants
Authors: Wu Hsin-Yen Larry , Jen Joey , Hsu Polly Yingshan 
Published: July 2023

Abstract
Translation is a crucial step in gene expression and plays a vital role in regulating various aspects of plant development and environmental responses. It is a dynamic and complex program that involves interactions between mRNAs, transfer RNAs, and the ribosome machinery through both cis- and trans-regulation while integrating internal and external signals. Translational control can act in a global (transcriptome-wide) or mRNA-specific manner. Recent advances in genome-wide techniques, particularly ribosome profiling and proteomics, have led to numerous exciting discoveries in both global and mRNA-specific translation. In this review, we aim to provide a “primer” that introduces readers to this fascinating yet complex cellular process and provide a big picture of how essential components connect within the network. We begin with an overview of mRNA translation, followed by a discussion of the experimental approaches and recent findings in the field, focusing on unannotated translation events and translational control through cis-regulatory elements on mRNAs and trans-acting factors, as well as signaling networks through 3 conserved translational regulators TOR, SnRK1, and GCN2. Finally, we briefly touch on the spatial regulation of mRNAs in translational control. Here, we focus on cytosolic mRNAs; translation in organelles and viruses is not covered in this review.
Multifidus dysfunction and restorative neurostimulation: a scoping review
Authors: Tieppo Francio Vinicius , Westerhaus Benjamin D , Carayannopoulos Alexios G , Sayed Dawood 
Published: July 2023

AbstractObjectiveChronic low back pain (CLBP) is multifactorial in nature, with recent research highlighting the role of multifidus dysfunction in a subset of nonspecific CLBP. This review aimed to provide a foundational reference that elucidates the pathophysiological cascade of multifidus dysfunction, how it contrasts with other CLBP etiologies and the role of restorative neurostimulation.MethodsA scoping review of the literature.ResultsIn total, 194 articles were included, and findings were presented to highlight emerging principles related to multifidus dysfunction and restorative neurostimulation. Multifidus dysfunction is diagnosed by a history of mechanical, axial, nociceptive CLBP and exam demonstrating functional lumbar instability, which differs from other structural etiologies. Diagnostic images may be used to grade multifidus atrophy and assess other structural pathologies. While various treatments exist for CLBP, restorative neurostimulation distinguishes itself from traditional neurostimulation in a way that treats a different etiology, targets a different anatomical site, and has a distinctive mechanism of action.ConclusionsMultifidus dysfunction has been proposed to result from loss of neuromuscular control, which may manifest clinically as muscle inhibition resulting in altered movement patterns. Over time, this cycle may result in potential atrophy, degeneration and CLBP. Restorative neurostimulation, a novel implantable neurostimulator system, stimulates the efferent lumbar medial branch nerve to elicit repetitive multifidus contractions. This intervention aims to interrupt the cycle of dysfunction and normalize multifidus activity incrementally, potentially restoring neuromuscular control. Restorative neurostimulation has been shown to reduce pain and disability in CLBP, improve quality of life and reduce health care expenditures.
Glucocorticoid treatment in SLE is associated with infections, comorbidities and mortality—a national cohort study
Authors: Frodlund Martina , Jönsen Andreas , Remkus Lauren , Telg Gunilla , Söderdahl Fabian , Leonard Dag 
Published: July 2023

Abstract

Objectives
Patients with SLE have an increased risk of comorbidities and impaired survival. We aimed to assess whether various thresholds of oral CS (OCS) can predict development of infections, comorbidities, malignancies and survival in SLE using data from national health registries in Sweden.

Methods
All incident SLE cases, age &gt;18 years, in Sweden (n = 5309) between 2005 and 2020 and matched population controls (n = 26 545) were included and followed until 2020, a total of 257 942 patient years. Data from national registers were retrieved including information from the National Prescribed Drug Register. Risk factors were analysed using time-dependent Cox regression models.

Results
Compared with no OCS, &gt;0 to &lt;5.0 mg/day, 5.0–7.5 mg/day as well as &gt;7.5 mg/day OCS predicted development of infections (pneumonia, influenza, herpes zoster and urinary tract infection), osteoporosis, osteonecrosis, gastroduodenal ulcers, cataracts, hypertension and mortality (all P &lt; 0.05). OCS &gt;0 to &lt;5.0 mg/day was associated with lower hazard ratios for these comorbidities than higher doses of OCS. Fifteen years after diagnosis, 48% of patients were taking OCS at a median dose of 5.7 mg/day. A small reduction of OCS treatment 5 years after diagnosis in patients diagnosed with SLE 2006–10 compared with 2011–15 was observed, 49% vs 46% respectively (P = 0.039).

Conclusion
Results highlight the potential harm associated with even low OCS dose treatment in SLE and the need to judiciously use OCS at the lowest possible dose to maximize efficacy and minimize harm.