bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphological Profiling of Unilateral Condylar Hyperplasia: Implications for Surgical Decision-Making
Authors: Sivakanthan Thiviya , Steinbacher Derek M.
Published: July 2024

Objective:

Unilateral condylar hyperplasia (UCH) presents challenges with functional and esthetic concerns, including facial and chin asymmetry, prognathism, class III malocclusion, and temporomandibular joint symptoms. This study aims to precisely locate condylar and mandibular asymmetry in patients with UCH, aiding targeted surgical correction and addressing persistent skeletal changes.

Methods:

This retrospective study analyzed data from patients with UCH and controls, utilizing high-quality cone beam computed tomography scans with 1 mm or fewer slices. Morphometric points were placed using Planmeca software, measuring linear distances on both affected and unaffected sides.

Results:

In a cohort of 40 patients (29 UCH, 11 controls), significant differences in condylar head and neck lengths were observed between the affected and unaffected sides in patients with UCH (P = 0.0019). However, ramus length showed no significant variation (P = 0.65). When comparing differences in condylar head and neck length between controls and patients with UCH, a substantial contrast was evident (P = 1.98e-07), while ramus length differences were not significant (P = 1.00). The median condylar head and neck lengths were 20.3 mm for controls, 19.78 mm for the unaffected side in patients with UCH, and 23.48 mm for the affected side.

Conclusion:

Facial asymmetry in UCH primarily results from differences in condylar head and neck length, not ramus length. This emphasizes the importance of high condylectomy in addition to bilateral sagittal split osteotomy to achieve improved symmetry and reduced temporomandibular joint dysfunction. Understanding these regional skeletal changes is critical for effective UCH treatment.
Using OR Black Box Technology to Determine Quality Improvement Outcomes for In-situ Timeout and Debrief Simulation
Authors: Campbell Krystle K. , Abreu Andres A. , Zeh Herbert J. , Daniel William C. , Palter Vanessa N. , Bishop Samantha J. , Sims Suzanne , Odeh Jaffer M. , Evans Kim , Dandekar Priya , Scott Daniel J.
Published: July 2024

Objective:

The purpose of this study was to determine quality improvement outcomes following the pilot implementation of an in-situ simulation designed to enhance surgical safety checklist performance.

Background:

OR Black Box (ORBB) technology allows near real-time assessment for surgical safety checklist performance. Before our study, timeout quality was 73.3%, compliance was 99.9%, and engagement was 89.7% (n=1993 cases); Debrief Quality was 76.0%, compliance was 66.9%, and engagement was 66.7% (n=1842 cases).

Methods:

This IRB-approved study used prospective convergent multi-methods. During 2 months, a 15-minute in-situ simulation, incorporating rapid cycle deliberate practice, was implemented for OR teams. ORBB analytics generated Timeout and Debrief scores for actual operations performed by surgeons who participated in simulation (Sim-group) versus those who did not (No-sim group) over 6 months, including 2 months pre-intervention, during-intervention, and post-intervention. Inductive content analysis was performed based on simulation discussions to determine team member perspectives.

Results:

Thirty simulations with 163 interprofessional participants were conducted. ORBB data from 1570 cases were analyzed. Scores were significantly better for the Sim-group compared with the No-sim group for debrief quality (84% vs. 79% P<0.001, during-intervention), compliance (73% vs. 66%, P<0.001, post-intervention), and engagement (80% vs. 73%, P=0.012, during-intervention). There were no between-group differences for Timeout scores. Thematic analysis identified 2 primary categories: “culture of safety” and “policy.”

Conclusions:

This simulation-based QI intervention created a psychologically safe training environment for OR teams. The novel use of ORBB technology facilitated outcome analysis and showed significantly better Debrief scores for simulation-trained surgeons compared with nontrained surgeons.
Peroral Endoscopic Myotomy: Short Versus Long Esophageal Myotomy for Achalasia Cardia: A Randomized Controlled Noninferiority Trial
Authors: Rai Praveer , Kumar Pankaj , Goel Amit , Singh Thakur Prashant , Mishra Prabhaker , Verma Prashant , Kumar Ajay , Kumar Vinod
Published: July 2024

Background and Aims:

The appropriate length of esophageal myotomy in peroral endoscopic myotomy (POEM) for achalasia cardia remains unclear. This study aimed to compare the outcome of short (≤3 cm) and long (≥6 cm) esophageal myotomy in patients with type I and II achalasia cardia.

Methods:

This single-blinded, randomized controlled noninferiority trial was conducted at a tertiary center between July 2021 and December 2021. Patients with achalasia types I and II were randomized into short (≤3 cm) and long (≥6 cm) esophageal myotomy groups. The primary outcome of the study was clinical success (Eckardt score ≤3) 1 year after the procedure. The secondary outcomes included a comparison of technical success, operating duration, occurrence of intraoperative adverse events, alterations in integrated relaxation pressure (IRP), change in barium column height after 5 minutes (1 mo), and gastroesophageal reflux disease (3 mo) between the groups.

Results:

Fifty-four patients were randomized into the short (n=27) or long (n=27) esophageal myotomy groups. Technical success rates were 100% (27/27) and 96.3% (26/27) in short myotomy (SM) and long myotomy (LM) groups, respectively. The clinical success rates were 96.3% (26/27) and 96.2% (25/26) in the SM and LM groups, respectively (P=0.998). The mean (±SD) length of the esophageal myotomy was 2.75±0.36 cm in the SM and 6.69±1.35 cm in the LM groups (P<0.001). The mean (±SD) procedure time for the SM and LM groups was 61.22±8.44 and 82.42±14.70 minutes (P<0.001), respectively. The mean integrated relaxation pressure (IRP), Eckardt score, adverse events, reflux esophagitis, symptomatic gastroesophageal reflux disease, and esophageal acid exposure (>6%) did not differ significantly between the 2 groups following POEM treatment.

Conclusions:

Short myotomy is noninferior to long myotomy in terms of clinical success, gastroesophageal reflux disease, and intraoperative adverse events at the short-term follow-up (P>0.05). Short myotomy resulted in a reduced operative time (P<0.05).
Racial and Ethnic Disparities in Sacrocolpopexy Approach
Authors: Nicola-Ducey Lauren , Nolan Olivia , Cichowski Sara , Osmundsen Blake
Published: July 2024

Importance

Racial inequity elevates risk for certain diagnoses and health disparities. Current data show disparities for Black women when comparing open versus minimally invasive hysterectomy. It is unknown if a similar disparity exists in surgical management of pelvic organ prolapse.

Objective

The objective of this study was to determine whether racial or ethnic disparities exist for open abdominal versus minimally invasive sacrocolpopexy.

Study Design

Cross-sectional data of the Healthcare Cost and Utilization Project National Inpatient Sample and the Nationwide Ambulatory Surgery Sample for the year 2019 was used. Bivariate analysis identified demographic and perioperative differences between abdominal versus minimally invasive sacrocolpopexy, which were compared in a multivariable logistic regression.

Results

Forty-one thousand eight hundred thirty-seven patients underwent sacrocolpopexy: 35,820 (85.6%), minimally invasive sacrocolpopexy, and 6,016, (14.4%) abdominal sacrocolpopexy. In an unadjusted analysis, Black patients were more likely to undergo an abdominal sacrocolpopexy compared to non-Hispanic White patients (OR 2.14, 95% CI 1.16–3.92, P <0.01). Hispanic patients were more likely to undergo abdominal sacrocolpopexy compared to non-Hispanic White patients (OR 1.69, 95% CI 1.26–2.26, P <0.001). Other factors associated with abdominal sacrocolpopexy are zip code quartile, payer status, composite comorbidity score, hospital control, and hospital bed size. In the regression model, Black patients remained more likely to undergo abdominal sacrocolpopexy compared to those who identified as White (aOR 2, 95% CI 1.26–3.16, P < 0.003). Hispanic patients were more likely to undergo abdominal sacrocolpopexy compared to those who identified as White (aOR 1.73, 95% CI 1.31–2.28, P < 0.001).

Conclusion

Abdominal sacrocolpopexy was more likely to occur in patients who identified as Black or Hispanic.
A Multicenter Training and Interrater Reliability Study of the BASED Score for Infantile Epileptic Spasms Syndrome
Authors: Mytinger John R. , Albert Dara V. F. , Aylward Shawn C. , Beatty Christopher W. , Bhalla Sonam , Bhatia Sonal , Brock Guy N. , Ciliberto Micheal A. , Choudhari Purva R. , Clark Daniel J. , Cohen Jennifer Madan , Czech Theresa M. , Fredwall Megan M. , Gonzalez-Giraldo Ernesto , Harini Chellamani , Hunter Senyene E. , Sandoval Karamian Amanda G. , Katyayan Akshat , Kistler Isaac , Kulkarni Neil , Liu Virginia B. , McCabe Corinne , Murray Thomas , Neville Kerri , Patel Shital H. , Pavuluri Spriha , Phillips Donald J. , Samanta Debopam , Sirsi Deepa , Spelbrink Emily M. , Stafstrom Carl E. , Steenari Maija , Takacs Danielle S. , Terrill Tyler , Tran Linh , Vidaurre Jorge , Shrey Daniel W.
Published: July 2024

Purpose:

The best possible outcomes in infantile epileptic spasms syndrome require electroclinical remission; however, determining electrographic remission is not straightforward. Although the determination of hypsarrhythmia has inadequate interrater reliability (IRR), the Burden of AmplitudeS and Epileptiform Discharges (BASED) score has shown promise for the reliable interictal assessment of infantile epileptic spasms syndrome. Our aim was to develop a BASED training program and assess the IRR among learners. We hypothesized moderate or better IRR for the final BASED score and the presence or absence of epileptic encephalopathy (+/−EE).

Methods:

Using a web-based application, 31 learners assessed 12 unmarked EEGs (length 1–6 hours) from children with infantile epileptic spasms syndrome.

Results:

For all readers, the IRR was good for the final BASED score (intraclass correlation coefficient 0.86) and +/−EE (Marginal Multirater Kappa 0.63). For all readers, the IRR was fair to good for all individual BASED score elements.

Conclusions:

These findings support the use of our training program to quickly learn the BASED scoring method. The BASED score may be a valuable clinical and research tool. Given that the IRR for the determination of epileptic encephalopathy is not perfect, clinical acumen remains paramount. Additional experience with the BASED scoring technique among learners and advances in collaborative EEG evaluation platforms may improve IRR.
Experience-dependent sex differences in the role of dorsal striatal dopamine D1 receptor activity in methamphetamine self-administration revealed by a novel TREND model
Authors: Madhuranthakam InduMithra , Job Martin O
Published: July 2024

BACKGROUND

The role of dorsal striatal dopamine D1 receptor systems in the mechanism of methamphetamine self-administration (METH SA), and sex differences in this role, are unclear. We hypothesized that this role would be sex and METH experience-dependent. Because prior experience regulates subsequent effects of drugs, we developed a novel model to account for this interaction, termed the TREND model (Time-Related-Experience-Normalized-Dynamics) for drug SA analysis. We tested our hypothesis by comparing results from the new TREND model and the current model.

METHODS

For model validation, we reanalyzed previous data (Job et al., 2020) with the aim of determining which model (current or TREND) was more effective as an analytical tool. We compared variables from each model with the effect of Clozapine-N-Oxide (CNO, chemogenetic ligand) on METH SA. We employed regression analysis, median split, ANOVA to see which could reveal sex and experience dependency of dorsal striatal dopamine D1 receptor system.

RESULTS

The current model variables were unrelated to CNO effect, with no sex differences in these relationships. TREND model revealed new variables that were unrelated to current variables but related to CNO effect on METH in males and females, with sex differences in these relationships. TREND, but not the current model, detected sex differences when comparing males and females with prior high, but not low, behavioral response variables.

CONCLUSIONS

TREND model is more sensitive than the current model for detecting experience-dependent sex differences in the role of the dorsal striatal dopamine D1 receptor systems in the mechanism of METH SA.
Decoding the Epigenetic Landscape: Insights into 5mC and 5hmC Patterns in Mouse Cortical Cell Types
Authors: Wei Xiaoran , Li Jiangtao , Cheng Zuolin , Wei Songtao , Yu Guoqiang , Olsen Michelle L
Published: July 2024

The DNA modifications, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), represent powerful epigenetic regulators of temporal and spatial gene expression. Yet, how the cooperation of these genome-wide, epigenetic marks determine unique transcriptional signatures across different brain cell populations is unclear. Here we applied Nanopore sequencing of native DNA to obtain a complete, genome-wide, single-base resolution atlas of 5mC and 5hmC modifications in neurons, astrocytes and microglia in the mouse cortex (99% genome coverage, 40 million CpG sites). In tandem with RNA sequencing, analysis of 5mC and 5hmC patterns across cell types reveals astrocytes drive uniquely high brain 5hmC levels and support two decades of research regarding methylation patterns, gene expression and alternative splicing, benchmarking this resource. As such, we provide the most comprehensive DNA methylation data in mouse brain as an interactive, online tool (NAM-Me,https://olsenlab.shinyapps.io/NAMME/) to serve as aresourcedataset for those interested in the methylome landscape.
Fully synthetic hydrogels promote robust crypt formation in intestinal organoids
Authors: Hushka Ella A , Blatchley Michael R , Macdougall Laura J , Yavitt F Max , Kirkpatrick Bruce E , Bera Kaustav , Dempsey Peter J , Anseth Kristi S
Published: July 2024

Initial landmark studies in the design of synthetic hydrogels for intestinal organoid culture identified precise matrix requirements for differentiation, namely decompression of matrix-imposed forces and supplementation of laminin. But beyond stating the necessity of laminin, organoid-laminin interactions have gone largely unstudied, as this ubiquitous requirement of exogenous laminin hinders investigation. In this work, we exploit a fast stress relaxing, boronate ester based synthetic hydrogel for the culture of intestinal organoids, and fortuitously discover that unlike all other synthetic hydrogels to date, laminin does not need to be supplemented for crypt formation. This highly defined material provides a unique opportunity to investigate laminin-organoid interactions and how it influences crypt evolution and organoid function. Via fluorescent labeling of non-canonical amino acids, we further show that adaptable boronate ester bonds increase deposition of nascent proteins, including laminin. Collectively, these results advance the understanding of how mechanical and matricellular signaling influence intestinal organoid development.
VISUALIZING GAUSSIAN-CHAIN LIKE STRUCTURAL MODELS OF HUMAN α-SYNUCLEIN IN MONOMERIC PRE-FIBRILLAR STATE: SOLUTION SAXS DATA AND MODELING ANALYSIS
Authors: Dey Madhumita , Gupta Arpit , Badmalia Maulik D. , Ashish  , Sharma Deepak
Published: July 2024

Here, using small angle X-ray scattering (SAXS) data profile as reference, we attempted to visualize conformational ensemble accessible prefibrillar monomeric state of α-synuclein in solution. In agreement with previous reports, our analysis also confirmed that α-synuclein molecules adopted disordered shape profile under non-associating conditions. Chain-ensemble modeling protocol with dummy residues provided two weighted averaged clusters of semi-extended shapes. Further, Ensemble Optimization Method (EOM) computed mole fractions of semi-extended “twisted” conformations which might co-exist in solution. Since these were only Cαtraces of the models, ALPHAFOLD2 server was used to search for all-atom models. Comparison with experimental data showed all predicted models disagreed equally, as individuals. Finally, we employed molecular dynamics simulations and normal mode analysis-based search coupled with SAXS data to seek better agreeing models. Overall, our analysis concludes that a shifting equilibrium of curved models with low α-helical content best-represents non-associating monomeric α-synuclein.
Pre-implantation genome-wide methylation enables environmental adaptation in a social meso-carnivore
Authors: Hung Tin Hang , Tsai Ming-shan , Newman Chris , Macdonald David W. , Buesching Christina D.
Published: July 2024

Many wild populations are increasingly stressed by rapid climatic change. While behavioural plasticity can enable limited tactical adaptive responses, standing genetic variation limits the species’ capacity to respond to climate change velocity. Epigenetic modification may provide a more rapid and plastic adaptive mechanism, but has been little studied in wild-living animals. Here we investigated CpG methylation during the pre-natal and early-life development of 95 European badger cubs between 2003 and 2011). During 10-months of delayed pre-implantation variability in precipitation between previous year’s February and April was the top determinant of methylation patterns among neonates, followed by mean temperature and temperature variability. Among the 4,641 significant weather-associated CpG sites, most occurred in the 47S rDNA region. Methylation of 47S rDNA was also associated with early-life weight, implying a mechanism that relays environmental stress to phenotypic stress. We also detected evidence for predictive adaptive response. Among the 1,641 CpG sites associated with early-life weight, pathways were associated with early-life growth, immune regulation, and to the development of aggression for competitive access to weather-limited food resources were over-represented. We conclude that a species’ epigenetics can have an important role in adaptive plasticity to environmental changes with important implications for biodiversity conservation and management.
Temporal-spatially metabolic reprogramming rewires the H3K27ac landscape to enable the initiation of liver regeneration
Authors: Zheng Qi , Li Xiaojiaoyang , Xu Zhenyu , Cai Yajie , Li Fanghong , Xue Xiaoyong , Li Shuo , Sun Rong , Fan Guifang , Wu Jianzhi , Qu Jiaorong , Liu Runping
Published: July 2024

The liver possesses extensive regenerative capacity. Nevertheless, the most proximal events driving the transition from quiescent to proliferative hepatocytes remain largely elusive. Using the combination of spatiotemporal metabolomics and transcriptomics, our study mapped out the temporal-spatial landscape of metabolic reprogramming, epigenetic remodeling, and transcriptomic rewiring from 3 to 12 hours post-partial hepatectomy. Specifically, we identified a profound metabolic shift towards hyperactive fatty acid oxidation (FAO) and suppressed phospholipid biosynthesis during the preparation phase of liver regeneration, which were surprisingly reversed afterwards. FAO-dependent accumulation of Acetyl-CoA particularly remodeled H3K27ac landscape. These metabolic reprograming and epigenetic regulation were spatially specific, aligning with the zonation of hepatocyte proliferation. Blocking FAO in etomoxir-treated or hepatocyte-specificCpt1aknockout mice, suppressing Acetyl-CoA biosynthesis, and inhibiting histone acetyltransferase all resulted in lethal liver regeneration deficiency. CUT&Tag analysis further revealed that the reshaping of H3K27ac profiles favored the transcription of genes associated with cell cycle transition and mitosis, and rewired the metabolic gene network. Collectively, we highlight a previously underappreciated role of FAO in epigenetic remodeling that is essential for the initiation of liver regeneration, offering exciting opportunity for the rescue of regeneration-deficient livers.

Graphical Abstract
Hair Cells Loss Estimation from Audiograms
Authors: Furst Miriam , Koral Yonatan , Zorea Asaf
Published: July 2024

Age-related hearing loss is characterized by a progressive loss of threshold sensitivity, especially at high frequencies. There is increasing evidence that the loss of cilia in the inner and outer hair cells is the dominant cause of hearing loss. We present a framework for calculating the human auditory threshold based on a non-linear time-domain cochlear model that incorporates hair cell damage along the cochlear partition. We successfully predicted the audiogram measured prior to death by substituting the postmortem percentage of surviving hair cells, using data from Wu et al. (Wuet al., 2020). We also present an algorithm for estimating the percentage of hair cells from a measured audiogram. Comparison with the data from Wu et al. revealed that the algorithm accurately predicted the surviving inner hair cells along the entire cochlear partition and the outer hair cells at the basal part of the cochlea.
Body oscillations reduce the aerodynamic power requirement of wild silkmoth flight
Authors: Sikandar Usama Bin , Aiello Brett R. , Sponberg Simon
Published: July 2024

Insects show diverse flight kinematics and morphologies reflecting their evolutionary histories and ecological adaptations. Many silkmoths utilizing low wingbeat frequencies and large wings to fly display body oscillations: Their bodies pitch and bob periodically – synchronized with their wing flapping cycle. Similar oscillations in butterflies augment weight support and thrust and reduce flight power requirements. However, how the instantaneous body and wing kinematics interact for these beneficial aerodynamic and power consequences is not well understood. We hypothesized that the body oscillations affect aerodynamic power requirements by influencing the wing rotation relative to the airflow. Using three-dimensional forward flight video recordings of four silkmoth species and a quasi-steady blade-element aerodynamic method, we found that the body pitch angle and the wing sweep angle maintain a narrow range of phase differences to enhance the angle of attack variation between each half-stroke due to enhanced wing rotation relative to the airflow. This redirects the aerodynamic force to increase upward and forward force during downstroke and upstroke respectively thus lowering the overall drag without compromising weight support and forward thrust. A reduction in energy expenditure is beneficial because adult silkmoths do not feed and rely on limited energy budgets.
Deletion of an evolutionarily conserved TAD boundary compromises spermatogenesis in mice
Authors: Lima Ana C. , Okhovat Mariam , Stendahl Alexandra M. , VanCampen Jake , Nevonen Kimberly A. , Herrera Jarod , Li Weiyu , Harshman Lana , Yang Ran , Fedorov Lev M. , Vigh-Conrad Katinka A. , Ahituv Nadav , Conrad Donald F. , Carbone Lucia
Published: July 2024

Spermatogenesis is a complex process that can be disrupted by genetic and epigenetic changes, potentially leading to male infertility. Recent research has rapidly increased the number of protein coding mutations causally linked to impaired spermatogenesis in humans and mice. However, the role of non-coding mutations remains largely unexplored. As a case study to evaluate the effects of non-coding mutations on spermatogenesis, we first identified an evolutionarily conserved topologically associated domain (TAD) boundary near two genes with important roles in mammalian testis function:Dmrtb1andLrp8. We then used CRISPR-Cas9 to generate a mouse line where 26kb of the boundary was removed including a strong and evolutionarily conserved CTCF binding site. ChIP-seq and Hi-C experiments confirmed the removal of the CTCF site and a resulting increase in the DNA-DNA interactions across the domain boundary. Mutant mice displayed significant changes in testis gene expression, abnormal testis histology, a 35% drop in the estimated efficiency of spermatogenesis and a 28% decrease in daily sperm production compared to littermate controls. Despite these quantitative changes in testis function, mutant mice show no significant changes in fertility. This suggests that non-coding deletions affecting testis gene regulation may have smaller effects on fertility compared to coding mutations of the same genes. Our results demonstrate that disruption of a TAD boundary can have a negative impact on sperm production and highlight the importance of considering non-coding mutations in the analysis of patients with male infertility.
Direct Percutaneous Embolization of Head, Neck and Spine Tumors: A Single Center Experience
Authors: Topiwala Karan , Huang Shiwei , Sabal Luke , Kahmeyer Bailey , Grande Andrew , Jagadeesan Bharathi
Published: July 2024

Introduction

Transarterial embolization is a well-established adjunct in the management of hypervascular head, neck, and spine tumors. Few case-series have described the role of direct percutaneous embolization (DPE).

Method

We report our experience with DPE (with or without transarterial embolization) in patients with head, neck, and spine tumors treated between 2012-2023. Baseline demographics, angiographic imaging, tumoral pathology, and relevant clinical variables were retrospectively reviewed and descriptively analyzed.

Result

A total of 55 patients underwent direct percutaneous embolization (19 of whom also received transarterial embolization either before [n=7] or after [n=12] DPE). The most commonly embolized lesions were malignant carcinomas (n=16), followed by juvenile nasopharyngeal angiofibromas (n=11), paragangliomas (n=8), hemangiomas (n=7), and others (hemangioblastoma, schwannoma, neurofibroma, esthesioneuroblastoma, meningioma and hemangiopericytoma). The most common locations were sinonasal/nasopharyngeal (n=21), followed by scalp/subcutaneous (n=18), carotid body (n=6), spinal/paraspinal (n=4), skull base (n=5), and intracranial (n=1). A median of 4 (interquartile range 4-6) twenty-two-gauge spinal needles were used per embolization with a median fluoroscopy time of 50.5 (23.2-77.8) minutes resulting in median radiation exposure of 3055 (840.5-5053.5) mGy. Seven patients received more than one embolic agent, withn-butyl cyanoacrylate (glue, n=44, 81.5%) being the mostly commonly used embolic, followed by ethylene-vinyl alcohol copolymer (Onyx, n=7, 12.9%), 98% dehydrated ethanol (n=7, 12.9%), sodium tetradecyl sulfate (n=2, 3.7%) and poly-vinyl alcohol particles (n=1, 1.8%). The median volume of embolic agent injected was 5.5(4-7.6) mL resulting in total/near-total (90%-99%) angiographic devascularization in 74.5% cases. The median operative blood-loss was 250(75-700) mL. One patient underwent trans-calavarial DPE for a cerebellar hemangioblastoma and suffered diffuse subarachnoid hemorrhage from profuse tumoral bleeding. One patient had an asymptomatic parent-vessel occlusion from retrograde embolic extension.

Conclusion

Our single-center study reinforces prior experience that DPE of Sino-nasal carcinomas, angiofibromas and paragangliomas with adhesive and non-adhesive liquid embolic agents is safe, feasible and effective. Further, it suggests that these benefits may also be extended to non-traditional head, neck and spine tumors. Caution must be exercised when applying these techniques to intracranial tumors with robust intratumoral arteriovenous shunting.
Trait genetic architecture and population structure determine model selection for genomic prediction in naturalArabidopsis thalianapopulations
Authors: Gibbs Patrick M. , Paril Jefferson F. , Fournier-level Alexandre
Published: July 2024

Genomic prediction applies to a wide range of agronomically relevant traits, with distinct ontologies and genetic architectures. Selecting the most appropriate model for the distribution of genetic effects and their associated allele frequencies in the training population is crucial. Linear regression models are often preferred for genomic prediction. However, linear models may not suit all genetic architectures and training populations. Machine Learning approaches have been proposed to improve genomic prediction owing to their capacity to capture complex biology including epistasis. However, the applicability of different genomic prediction models, including non-linear/non-parametric approaches, have not been rigorously assessed across a wide variety of plant traits in natural outbreeding populations. This study evaluates genomic prediction sensitivity to trait ontology and the impact of population structure on model selection and prediction accuracy. Examining 36 quantitative traits measured for 1000+ natural genotypes of the model plantArabidopsis thaliana, we assessed the performance of penalised regression, random forest, and multilayer perceptron at producing genomic predictions. Regression models were generally the most accurate, except for biochemical traits where random forest performed best. We link this result to the genetic architecture of each trait – notably that biochemical traits have simpler genetic architecture than macroscopic traits. Moreover, complex macroscopic traits, particularly those related to flowering and yield, were strongly correlated to population structure, while molecular traits were better predicted by fewer, independent markers. This study highlights the relevance of machine learning approaches for simple molecular traits and underscores the need to consider ancestral population history when designing training samples.

Article summary

Machine learning and linear models were tested for genomic prediction of multiple traits in the model plantArabidopsis thaliana. We associate the performance of genomic prediction models to trait ontology, finding machine learning approaches applicable to biochemical traits, and linear models best for macroscopic traits. We link this result to the genetic architecture of each trait and patterns of selection in the association panel’s ancestral population, thus underscoring the relevance of these two sensitivities to genomic prediction in plant breeding.
Local genetic adaptation to habitat in wild chimpanzees
Authors: Ostridge Harrison J. , Fontsere Claudia , Lizano Esther , Soto Daniela C. , Schmidt Joshua M. , Saxena Vrishti , Alvarez-Estape Marina , Barratt Christopher D. , Gratton Paolo , Bocksberger Gaëlle , Lester Jack D. , Dieguez Paula , Agbor Anthony , Angedakin Samuel , Assumang Alfred Kwabena , Bailey Emma , Barubiyo Donatienne , Bessone Mattia , Brazzola Gregory , Chancellor Rebecca , Cohen Heather , Coupland Charlotte , Danquah Emmanuel , Deschner Tobias , Dotras Laia , Dupain Jef , Egbe Villard Ebot , Granjon Anne-Céline , Head Josephine , Hedwig Daniela , Hermans Veerle , Hernandez-Aguilar R. Adriana , Jeffery Kathryn J. , Jones Sorrel , Junker Jessica , Kadam Parag , Kaiser Michael , Kalan Ammie K. , Kambere Mbangi , Kienast Ivonne , Kujirakwinja Deo , Langergraber Kevin E. , Lapuente Juan , Larson Bradley , Laudisoit Anne , Lee Kevin C. , Llana Manuel , Maretti Giovanna , Martín Rumen , Meier Amelia , Morgan David , Neil Emily , Nicholl Sonia , Nixon Stuart , Normand Emmanuelle , Orbell Christopher , Ormsby Lucy Jayne , Orume Robinson , Pacheco Liliana , Preece Jodie , Regnaut Sebastien , Robbins Martha M. , Rundus Aaron , Sanz Crickette , Sciaky Lilah , Sommer Volker , Stewart Fiona A. , Tagg Nikki , Tédonzong Luc Roscelin , van Schijndel Joost , Vendras Elleni , Wessling Erin G. , Willie Jacob , Wittig Roman M. , Yuh Yisa Ginath , Yurkiw Kyle , Vigilant Linda , Piel Alex , Boesch Christophe , Kühl Hjalmar S. , Dennis Megan Y. , Marques-Bonet Tomas , Arandjelovic Mimi , Andrés Aida M.
Published: July 2024

How populations adapt to their environment is a fundamental question in biology. Yet we know surprisingly little about this process, especially for endangered species such as non-human great apes. Chimpanzees, our closest living relatives, are particularly interesting because they inhabit diverse habitats, from rainforest to woodland-savannah. Whether genetic adaptation facilitates such habitat diversity remains unknown, despite having wide implications for evolutionary biology and conservation. Using 828 newly generated exomes from wild chimpanzees, we find evidence of fine-scale genetic adaptation to habitat. Notably, adaptation to malaria in forest chimpanzees is mediated by the same genes underlying adaptation to malaria in humans. This work demonstrates the power of non-invasive samples to reveal genetic adaptations in endangered populations and highlights the importance of adaptive genetic diversity for chimpanzees.

One-Sentence Summary

Chimpanzees show evidence of local genetic adaptation to habitat, particularly to pathogens, such as malaria, in forests.
A unique mechanism of snRNP core assembly
Authors: Wang Yingzhi , Chen Xiaoshuang , Kong Xi , Chen Yunfeng , Xiang Zixi , Xiang Yue , Hu Yan , Hou Yan , Zhou Shijie , Shen Congcong , Mu Li , Su Dan , Zhang Rundong
Published: July 2024

The assembly of spliceosomal snRNP cores involves seven Sm proteins (D1/D2/F/E/G/D3/B) forming a ring around each snRNA and typically requires several essential assembly chaperones, particularly the SMN-Gemins complex implicated in spinal muscular atrophy (SMA). Strikingly, in budding yeast, snRNP core assembly only involves Brr1, a nonessential homolog of Gemin2. To unravel this enigma, we systematically investigated snRNP core assembly in budding yeast using biochemical and genetic approaches. We discovered two distinct pathways in budding yeast: chaperone-mediated and direct. The chaperone-mediated pathway involves two proteins, Brr1 and a novel protein, Lot5, but is inefficient. Lot5 binds D1/D2/F/E/G to form a heterohexameric ring (6S). Brr1 binds D1/D2/F/E/G and 6S but cannot displace Lot5 to facilitate assembly. Disruption of both BRR1 and LOT5 genes caused mild growth retardation, but LOT5 overexpression substantially impeded growth. The direct pathway uniquely involves F/E/G as a trimer and a stable D1/D2/F/E/G intermediate complex, explaining the non-essentiality of assembly chaperones. These findings unveil a unique assembly mechanism of snRNP cores, illuminate the evolution of assembly chaperones, and suggest avenues for studying SMA pathophysiology.
Reconstruction and identification of the native PLP synthase complex from Methanosarcina acetivorans lysate
Authors: Agnew Angela , Humm Ethan , Zhou Kang , Gunsalus Robert P. , Zhou Z. Hong
Published: July 2024

Many protein-protein interactions behave differently in biochemically purified forms as compared to theirin vivostates. As such, determining native protein structures may elucidate structural states previously unknown for even well-characterized proteins. Here we apply the bottom-up structural proteomics method,cryoID, toward a model methanogenic archaeon. While they are keystone organisms in the global carbon cycle and active members of the human microbiome, there is a general lack of characterization of methanogen enzyme structure and function. Through thecryoIDapproach, we successfully reconstructed and identified the nativeMethanosarcina acetivoranspyridoxal 5’-phosphate (PLP) synthase (PdxS) complex directly from cryogenic electron microscopy (cryoEM) images of fractionated cellular lysate. We found that the native PdxS complex exists as a homo-dodecamer of PdxS subunits, and the previously proposed supracomplex containing both the synthase (PdxS) and glutaminase (PdxT) was not observed in cellular lysate. Our structure shows that the native PdxS monomer fashions a single 8α/8β TIM-barrel domain, surrounded by seven additional helices to mediate solvent and interface contacts. A density is present at the active site in the cryoEM map and is interpreted as ribose 5-phosphate. In addition to being the first reconstruction of the PdxS enzyme from a heterogeneous cellular sample, our results reveal a departure from previously published archaeal PdxS crystal structures, lacking the 37 amino acid insertion present in these prior cases. This study demonstrates the potential of applying thecryoIDworkflow to capture native structural states at atomic resolution for archaeal systems, for which traditional biochemical sample preparation is nontrivial.
Characteristics of Suicide Prevention Apps: A Content Analysis of Apps Available in Canada and the United Kingdom
Authors: Bennett-Poynter Laura , Groves Samantha , Kemp Jessica , Shin Hwayeon Danielle , Sequeira Lydia , Lascelles Karen , Strudwick Gillian
Published: July 2024

Objective

We aimed to examine the characteristics, features, and content of suicide prevention mobile apps available in app stores in Canada and the United Kingdom.

Design

Suicide prevention apps were identified from Apple and Android app stores between March-April 2023. Apps were screened against predefined inclusion criteria, and duplicate apps were removed. Data were then extracted based on descriptive (e.g., genre, app developer), security (e.g., password protection), and design features (e.g., personalization options). Content of apps were assessed using the Essential Features Framework. Extracted data were analyzed using a content analysis approach including narrative frequencies and descriptive statistics.

Results

Fifty-two (n=52) suicide prevention apps were included within the review. Most were tailored for the general population and were in English language only. One app had the option to increase app accessibility by offering content presented using sign language. Many apps allowed some form of personalization by adding text content, however most did not facilitate further customization such as the ability to upload photo and audio content. All identified apps included content from at least one of the domains of the Essential Features Framework. The most commonly included domains were sources of suicide prevention support, and information about suicide. The domain least frequently included was screening tools followed by wellness content. No identified apps had the ability to be linked to patient medical records.

Conclusions

The findings of this research present implications for the development of future suicide prevention apps. Development of a co-produced suicide prevention app which is accessible, allows for personalization, and can be integrated into clinical care may present an opportunity to enhance suicide prevention support for individuals experiencing suicidal thoughts and behaviours.

Article Summary

Strengths and limitations of this study

This app review used an established method for systematically identifying and examining suicide prevention apps, which has been successfully used previously.

There is potential for overlap between different domains of the Essential Features Framework, which could lead to changes in reporting of percentages relating to app review findings.

Only apps available in the UK and Canada in the English language were assessed. Current provision and content of suicide prevention apps may differ across countries, including those available in lower- and middle-income countries.

Due to resource and time constraints, the quality of apps were not assessed.
The Safety, Effectiveness and Prognostic Factors of Intravitreal Avastin (Bevacizumab) Injection for the Treatment of Macular Edema at the University of Gondar Tertiary Eye Care and Training Center, NW Ethiopia
Authors: Gizachew Yoseph , Tsegaw Asamere , Wuletaw Tarekegn
Published: July 2024

Introduction

The current management of macular edema (ME) is intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs and this represents an important advance in the treatment of ME.

Studies done in the western eye care settings have confirmed that intravitreal injection of Avastin is effective for the treatment of ME. However, data on this drug’s efficacy and safety in African eye care settings are very scarce.

Objective

To assess the Safety and Effectiveness of intravitreal Bevacizumab (Avastin) injection for the treatment of Macular Edema (ME) due to retina vascular diseases at university of Gondar tertiary eye care and training center, NW Ethiopia.

Method

A retrospective study was done on patients who were given intravitreal avastin (IVA) for the treatment of diabetic macular edema (DME), retinal vein occlusion (RVO) and Neovascular Age related macular degeneration (AMD). The main outcome measure was visual acuity (VA) and central macular thickness (CMT) measured by spectral domain OCT.

Results

Medical records of 50 patients (66 eyes) were reviewed of which 46 (69.7%) were males and mean age of 54.2 years (range 20-80). The means of baseline VA and CMT were 1.0logMAR and 379.4 µm respectively. At the end of follow up and after mean injection of 2.5 times per eye, the mean VA improved to 0.7 logMAR (p=0.001) and the mean CMT reduced to 295 µm (p=0.0001). Baseline mean VA was significant prognostic factor for VA improvement (p=0.0001). Baseline mean CMT (P=0.007), number of injection (P=0.009) and diffuse macular edema (P=0.03) were significant factors for CMT reduction.

Conclusions

IVA injection for ME edema due to retinal vascular diseases resulted in a significant improvement in mean VA (p=0.001) and CMT (p=0.0001) at the end of follow up. There was no any ocular or systemic complication of IVA injection.
Environmental differences impactAcinetobacter baumanniiphage isolation and infectivity
Authors: Alseth Ellinor O , Roush Carli , Irby Iris , Kopylov Mykhailo , Bobe Daija , Nguyen Kristy , Xu Huaijin , Bryksin Anton V , Rather Philip N
Published: July 2024

With the global rise of antimicrobial resistance, phage therapy is increasingly re-gaining traction as a strategy to treat bacterial infections. For phage therapy to be successful however, we first need to isolate appropriate candidate phages for both clinical and experimental research. Acinetobacter baumanniiis an opportunistic pathogen known for its ability to rapidly evolve resistance to antibiotics, making it a prime target for phage therapy. Yet phage isolation is often hampered byA. baumannii’s ability to rapidly switch between capsular states. Here, we report the discovery and structural characterisation of a novel lytic phage, Mystique. This phage was initially isolated against the wild-type AB5075: a commonly used clinical model strain against which no phage has previously been readily available for the capsulated form. When screening Mystique on 103 highly diverse isolates ofA. baumannii, we found that it has a broad host range, being able to infect 85.4% of all tested strains when tested on bacterial lawns – a host range which expanded to 91.3% when tested in liquid culture. This variation between solid and liquid environments on phage infectivity was also observed for several other phages in our collection that were assumed unable to infect AB5075, and capsule negative mutants that initially seemed completely resistant to Mystique proved susceptible when assayed in liquid. Overall, through the discovery of a novel phage we demonstrate how environmental differences can drastically impact phage infectivity with important consequences for phage isolation and characterisation efforts.

Author summary

Bacterial infections caused byAcinetobacter baumanniiare a major global health concern due to high antibiotic resistance, earning it a critical priority pathogen ranking by the WHO. Phage therapy is resurging as a treatment option, with some success againstA. baumannii. However, the wild-type clinical model strain used to assess new therapies lacks an available phage, and isolating phages forA. baumanniiis challenging due to its complex capsule. Here, we report the discovery of a novel lytic phage, Mystique, which exhibits a broad host range, infecting 94 out of 103 testedA. baumanniistrains. We conducted genomic sequencing and structural analysis to fully characterise Mystique. Additionally, we found that the testing environment significantly impacts results; some phages that do not form plaques on bacterial lawns can still infect and amplify in liquid cultures of the same strain. Moreover, mutants resistant to Mystique based on plaque assays were susceptible in liquid culture assays. This work underscores the necessity of a multifaceted approach for phage isolation and characterisation, as traditional phage assays may not be sufficient for studying bacteria-phage dynamics in certain bacteria such asA. baumannii.
Maternal prenatal stress induces sex-dependent changes in tRNA fragment families and cholinergic pathways in newborns
Authors: Vaknine Treidel Shani , Lobmaier Silvia , Sharma Ritika , Madrer Nimrod , Shulman Dana , Greenberg Pnina , Bennett Estelle R , Greenberg David S , Turjeman Adi , Zelgert Camilla , Zimmermann Peter , Frasch Martin G , Carmel Liran , Antonelli Marta C , Soreq Hermona
Published: July 2024

Maternal perceived prenatal stress (PPS) is a known risk factor for diverse developmental impairments in newborns, but the underlying molecular processes are incompletely understood. Here, we report that maternal PPS altered the birth profiles of blood transfer RNA fragments (tRFs), 16-50nt long non-random cleavage products of tRNAs, in a sex-dependent manner. Importantly, comparing stressed versus control maternal and umbilical cord blood serum presented alterations that were not limited to individual tRFs, but rather reflected selective changes in particular tRF families grouped by their mitochondrial or nuclear genome origin, parental tRNA coded amino acid, and cleavage type. tRF families that show stress- and sex-specific effects, revealed shared length and expression patterns which were strongest in the female newborns. Several of these tRFs carry complementary motifs to specific cholinergic mRNAs, suggesting possible translational regulation similar to microRNAs. Compatible with the cholinergic regulation of stress reactions, those "CholinotRFs" achieved an AUC of 95% when classifying female newborns according to maternal PPS. Moreover, we found altered catalytic activity of serum acetylcholinesterase, which was particularly elevated in male newborns, marking a second sex-specific effect. Our findings demonstrate an association of tRF families' patterns with newborns' sex-specific stress response to PPS and may lead to better diagnosis and therapeutic tools for these and other stressors.