bluuebunny/crossref_metadata_2025 huggingface dataset:
Medial and lateral dual plating of native distal femur fractures: a systematic literature review
Authors: O'Neill Dillon C. , Hakim Anne J. , DeKeyser Graham J. , Steffenson Lillia N. , Schlickewei Carsten W. , Marchand Lucas S. , Barg Alexej , Haller Justin M.
Published: January 2023

Introduction:

Lateral locked plating (LLP) development has improved outcomes for distal femur fractures. However, there is still a modest rate of nonunion in fractures treated with LLP alone, with higher nonunion risk in high-energy fractures, intra-articular involvement, poor bone quality, severe comminution, or bone loss. Several recent studies have demonstrated both the safety and the biomechanical advantage of dual medial and lateral plating (DP). The purpose of this study was to evaluate the clinical outcomes of DP for native distal femoral fractures by performing a systematic review of the literature.

Methods:

Studies reporting clinical outcomes for DP of native distal femur fractures were identified and systematically reviewed. Publications without full-text manuscripts, those solely involving periprosthetic fractures, or fractures other than distal femur fractures were excluded. Fracture type, mean follow-up, open versus closed fracture, number of bone grafting procedures, nonunion, reoperation rates, and complication data were collected. Methodologic study quality was assessed using the Coleman methodology score.

Results:

The initial electronic review and reverse inclusion protocol identified 1484 publications. After removal of duplicates and abstract review to exclude studies that did not discuss clinical treatment of femur fractures with dual plating, 101 potential manuscripts were identified and manually reviewed. After final review, 12 studies were included in this study. There were 199 fractures with average follow-up time of 13.72 months. Unplanned reoperations and nonunion occurred in 19 (8.5%) and 9 (4.5%) cases, respectively. The most frequently reported complications were superficial infection (n = 6, 3%) and deep infection (n = 5, 2.5%) postoperatively. Other complications included delayed union (n = 6, 3%) not requiring additional surgical treatment and knee stiffness in four patients (2%) necessitating manipulation under anesthesia or lysis of adhesions. The average Coleman score was 50.5 (range 13.5–72), suggesting that included studies were of moderate-to-poor quality.

Conclusions:

Clinical research interest in DP of distal femoral fractures has markedly increased in the past few decades. The current data suggest that DP of native distal femoral fractures is associated with favorable nonunion and reoperation rates compared with previously published rates associated with LLP alone. In the current review, DP of distal femoral fractures was associated with acceptable rates of complications and generally good functional outcomes. More high-quality, directly comparable research is necessary to validate the conclusions of this review.
Chronic pain concepts of pediatricians: a qualitative survey
Authors: Locher Cosima , Wörner Andreas , Carlander Maria , Kossowsky Joe , Dratva Julia , Koechlin Helen
Published: January 2023

Introduction:

Chronic pain is a prevalent, yet underrecognized, condition in children and adolescents. A biopsychosocial framework has been widely adopted over the past decades and resulted in a new pain classification in the International Classification of Diseases, 11th revision (ICD-11). Nevertheless, little is known about pediatricians' pain concepts.

Objectives:

We explored pain concepts of Swiss pediatricians by means of a qualitative analysis.

Method:

A cross-sectional online survey was sent to clinically active Swiss pediatricians registered with the Swiss Society for Pediatrics. A case vignette of a girl with chronic musculoskeletal pain was presented and pediatricians were asked (1) what they think caused the pain, and (2) how they would explain the pain to the patient and their family. Structuring content analysis was applied to describe major themes within the answers.

Results:

The following main categories emerged: psychological factors, biological factors, unclear etiology, social context, disorder specific, and multifactorial. Most pediatricians reported the belief that psychological factors explained the pain. However, when explaining the pain to the patient, biological factors were reported most often.

Conclusion:

There is a discrepancy between pediatricians' conviction that chronic pain is mostly explained by psychological factors and their exploratory model towards patients that focuses on biological factors. Promoting the biopsychosocial framework of chronic pain is key to ensure timely and effective treatment. The new pain classification in the ICD-11 has the potential to increase the use of the biopsychosocial model.
Clinical Feasibility of Automated Brain Tissue and Myelin Volumetry of Normal Brian Using Synthetic Magnetic Resonance Imaging With Fast Imaging Protocol: A Single-Center Pilot Study
Authors: Zheng Zuofeng , Yang Jiafei , Zhang Dongpo , Ma Jun , Yin Hongxia , Wang Zhenchang
Published: January 2023

Objective

This study aimed to investigate the clinical feasibility of synthetic magnetic resonance imaging (MRI) with fast imaging protocol for automated brain tissue and myelin volumetry in healthy volunteers at 3.0-T MRI.

Methods

Thirty-four healthy volunteers were scanned using synthetic MRI with 3 sets of scan parameters: groups Fast (FAS; 2 minutes, 29 seconds), Routine (ROU; 4 minutes, 7 seconds), and Research (RES; 7 minutes, 46 seconds). White matter (WM), gray matter (GM), cerebrospinal fluid (CSF), non-WM/GM/CSF (NoN), brain parenchymal volume (BPV), intracranial volume (ICV), and myelin volume (MYV) were compared between 3 groups. Linear correlation analysis was performed for measured volumes of groups FAS and ROU versus group RES.

Results

Significant differences were found in all the measured brain tissue volumes between groups FAS and ROU (P < 0.001), FAS and RES (P < 0.05), and ROU and RES (P < 0.05), except for NoN between groups ROU and RES (P = 0.0673), ICV between groups FAS and ROU (P = 0.2552), and ICV between groups FAS and RES (P = 0.4898). The intergroup coefficients of variation were 4.36% for WM, 6.39% for GM, 10.14% for CSF, 67.5% for NoN, 1.21% for BPV, 0.08% for ICV, and 5.88% for MYV. Strong linear correlation was demonstrated for WM, GM, CSF, BPV, ICV, and MYV (R = 0.9230–1.131) between FAS versus RES, and ROU versus RES.

Conclusions

Using synthetic MRI with fast imaging protocol can change the measured brain tissue volumes of volunteers. It is necessary to use consistent acquisition protocols for comparing or following up cases quantitatively.
Environmental Impact and Cost Savings of Operating Room Quality Improvement Initiatives: A Scoping Review
Authors: Sullivan Gwyneth A , Petit Hayley J , Reiter Audra J , Westrick Jennifer C , Hu Andrew , Dunn Jennifer B , Gulack Brian C , Shah Ami N , Dsida Richard , Raval Mehul V
Published: January 2023

BACKGROUND:

Operating rooms are major contributors to a hospital’s carbon footprint due to the large volumes of resources consumed and waste produced. The objective of this study was to identify quality improvement initiatives that aimed to reduce the environmental impact of the operating room while decreasing costs.

STUDY DESIGN:

A literature search was performed using PubMed, Scopus, CINAHL, and Google Scholar and included broad terms for “operating room,” “costs,” and “environment” or “sustainability.” The “triple bottom line” framework, which considers the environmental, financial, and social impacts of interventions to guide decision making, was used to inform data extraction. The studies were then categorized using the 5 “Rs” of sustainability—refuse, reduce, reuse, repurpose, and recycle—and the impacts were discussed using the triple bottom line framework.

RESULTS:

A total of 23 unique quality improvement initiatives describing 28 interventions were included. Interventions were categorized as “refuse” (n = 11; 39.3%), “reduce” (n = 8; 28.6%), “reuse” (n = 3; 10.7%), and “recycle” (n = 6; 21.4%). While methods of measuring environmental impact and cost savings varied greatly among studies, potential annual cost savings ranged from $873 (intervention: education on diverting recyclable materials from sharps containers; environmental impact: 11.4 kg sharps waste diverted per month) to $694,141 (intervention: education to reduce regulated medical waste; environmental impact: 30% reduction in regulated medical waste).

CONCLUSIONS:

Quality improvement initiatives that reduce both cost and environmental impact have been successfully implemented across a variety of centers both nationally and globally. Surgeons, healthcare practitioners, and administrators interested in environmental stewardship and working toward a culture of sustainability may consider similar interventions in their institutions.
Setting the Standard for Cutaneous Melanoma Wide Local Excision: An Overview of the American College of Surgeons Commission on Cancer Standard 5.5
Authors: Lillemoe Heather A , Williams Jelani K , Teshome Mediget K , Zheng Linda , Francescatti Amanda B , Hieken Tina J , Katz Matthew HG , Hunt Kelly H , Vreeland Timothy J , Asare Elliot A
Published: January 2023

The purpose of this article is to review the objectives of the American College of Surgeons Commission on Cancer Operative Standards with a specific focus on Standard 5.5, which pertains to curative intent wide local excision of primary cutaneous melanoma lesions. We review the details and rationale of the standard itself, including its requirement to include specific elements and responses in synoptic format in operative reports.
A global perspective on bacterial diversity in the terrestrial deep subsurface
Authors: Soares A. , Edwards A. , An D. , Bagnoud A. , Bradley J. , Barnhart E. , Bomberg M. , Budwill K. , Caffrey S. M. , Fields M. , Gralnick J. , Kadnikov V. , Momper L. , Osburn M. , Mu A. , Moreau J. W. , Moser D. , Purkamo L. , Rassner S. M. , Sheik C. S. , Sherwood Lollar B. , Toner B. M. , Voordouw G. , Wouters K. , Mitchell A. C.
Published: January 2023

While recent efforts to catalogue Earth’s microbial diversity have focused upon surface and marine habitats, 12–20 % of Earth’s biomass is suggested to exist in the terrestrial deep subsurface, compared to ~1.8 % in the deep subseafloor. Metagenomic studies of the terrestrial deep subsurface have yielded a trove of divergent and functionally important microbiomes from a range of localities. However, a wider perspective of microbial diversity and its relationship to environmental conditions within the terrestrial deep subsurface is still required. Our meta-analysis reveals that terrestrial deep subsurface microbiota are dominated by Betaproteobacteria, Gammaproteobacteria and

Firmicutes

, probably as a function of the diverse metabolic strategies of these taxa. Evidence was also found for a common small consortium of prevalent

Betaproteobacteria

and

Gammaproteobacteria

operational taxonomic units across the localities. This implies a core terrestrial deep subsurface community, irrespective of aquifer lithology, depth and other variables, that may play an important role in colonizing and sustaining microbial habitats in the deep terrestrial subsurface. An in silico contamination-aware approach to analysing this dataset underscores the importance of downstream methods for assuring that robust conclusions can be reached from deep subsurface-derived sequencing data. Understanding the global panorama of microbial diversity and ecological dynamics in the deep terrestrial subsurface provides a first step towards understanding the role of microbes in global subsurface element and nutrient cycling.
Random Forest approach for the identification of relationships between epigenetic marks and its application to robust assignment of chromatin states
Authors: Saavedra Leandro Murgas , Pollastri Gianluca , Riquelme Erick , Sáez Mauricio , Martin Alberto J.M.
Published: January 2023

Structural changes of chromatin modulate access to DNA for all proteins involved in transcription. These changes are linked to variations in epigenetic marks that allow to classify chromatin in different functional states depending on the pattern of these marks. Importantly, alterations in chromatin states are known to be linked with various diseases. For example, there are abnormalities in epigenetic patterns in different types of cancer. For most of these diseases, there is not enough epigenomic data available to accurately determine chromatin states for the cells affected in each of them, mainly due to high costs of performing this type of experiments but also because of lack of a sufficient amount of sample or degradation thereof.

In this work we describe a cascade method based on a random forest algorithm to infer epigenetic marks, and by doing so, to reduce the number of experimentally determined marks required to assign chromatin states. Our approach identified several relationships between patterns of different marks, which strengthens the evidence in favor of a redundant epigenetic code.
Divergence of alternative sugar preferences through modulation of the expression and activity of the Gal3 sensor in yeast
Authors: Fita-Torró Josep , Swamy Krishna B. S. , Pascual-Ahuir Amparo , Proft Markus
Published: January 2023

Optimized nutrient utilization is crucial for the progression of microorganisms in competing communities. Here we investigate how different budding yeast species and ecological isolates have established divergent preferences for two alternative sugar substrates: Glucose, which is fermented preferentially by yeast, and galactose, which is alternatively used upon induction of the relevantGALmetabolic genes. We quantified the dose-dependent induction of theGAL1gene encoding the central galactokinase enzyme, and found that a very large diversification exists between different yeast ecotypes and species. The sensitivity ofGAL1induction correlates with the growth performance of the respective yeasts with the alternative sugar. We further define some of the mechanisms, which have established different glucose/galactose consumption strategies in representative yeast strains by modulating the activity of the Gal3 inducer. (1) Optimal galactose consumers, such asSaccharomyces bayanus, contain a hyperactiveGAL3promoter, sustaining highly sensitiveGAL1expression, which is not further improved upon repetitive galactose encounters. (2) Desensitized galactose consumers, such asS. cerevisiaeY12, contain a less sensitive Gal3 sensor, causing a shift of the galactose response towards higher sugar concentrations even in galactose experienced cells. (3) Galactose insensitive sugar consumers, such asS. cerevisiaeDBVPG6044, contain an interruptedGAL3gene, causing extremely reluctant galactose consumption, which however still is improved upon repeated galactose availability. In summary, different yeast strains and natural isolates have evolved galactose utilization strategies, which cover the whole range of possible sensitivities by modulating the expression and/or activity of the inducible galactose sensor Gal3.
DReAmocracy: A Method to Capitalize on Prior Drug Discovery Efforts to Highlight Candidate Drugs for Repurposing
Authors: Savva Kyriaki , Zachariou Margarita , Bourdakou Marilena , Dietis Nikolas , Spyrou George M.
Published: January 2023

In the area of drug research, several computational drug repurposing studies have highlighted candidate repurposed drugs, as well as drugs from clinical trial studies in different phases. To our knowledge, the aggregation of the proposed lists of drugs by previous studies has not been extensively exploited towards the generation of a dynamic reference matrix regarding the disease-related frequencies of drug features such as the modes of action, the initial indications and the targeted pathways. To fill this knowledge gap, we performed a weight-modulated majority voting of the modes of action, initial indications and targeted pathways of the drugs in a well-known repository, namely the Drug Repurposing Hub. Our method, DReAmocracy, exploits this pile of information and creates frequency tables and finally a disease suitability score for each drug. As a testbed, we applied this method to a group of neurodegenerative diseases (Alzheimer’s, Parkinson’s, Huntington’s and Multiple Sclerosis). A super-reference table with drug suitability scores has been created for all four neurodegenerative diseases and can be queried for any drug candidate against them. Top-scored drugs for Alzheimer’s disease includeagomelatineandmirtazapine, for Parkinson’s diseaseapomorphineandpramipexole, for Huntington’sfluphezineandperphezine, and for Multiple Sclerosiszonisamideanddisopyramide. Overall, DReAmocracy is a methodology that leverages the existing experimental and/or computational knowledge (1) to reveal trends in selected tracks of drug discovery research that includes modes of action, targeted pathways and initial indications for the investigated drugs and (2) to score new candidate drugs for repurposing against a selected disease.
Integrative Multiomics to Dissect the Lung Transcriptional Landscape of Pulmonary Arterial Hypertension
Authors: Hong Jason , Wong Brenda , Rhodes Christopher J. , Kurt Zeyneb , Schwantes-An Tae-Hwi , Mickler Elizabeth A. , Gräf Stefan , Eyries Mélanie , Lutz Katie A. , Pauciulo Michael W. , Trembath Richard C. , Montani David , Morrell Nicholas W. , Wilkins Martin R. , Nichols William C. , Trégouët David-Alexandre , Aldred Micheala A. , Desai Ankit A. , Tuder Rubin M. , Geraci Mark W. , Eghbali Mansoureh , Stearman Robert S. , Yang Xia
Published: January 2023

Pulmonary arterial hypertension (PAH) remains an incurable and often fatal disease despite currently available therapies. Multiomics systems biology analysis can shed new light on PAH pathobiology and inform translational research efforts. Using RNA sequencing on the largest PAH lung biobank to date (96 disease and 52 control), we aim to identify gene co-expression network modules associated with PAH and potential therapeutic targets. Co-expression network analysis was performed to identify modules of co-expressed genes which were then assessed for and prioritized by importance in PAH, regulatory role, and therapeutic potential via integration with clinicopathologic data, human genome-wide association studies (GWAS) of PAH, lung Bayesian regulatory networks, single-cell RNA-sequencing data, and pharmacotranscriptomic profiles. We identified a co-expression module of 266 genes, called the pink module, which may be a response to the underlying disease process to counteract disease progression in PAH. This module was associated not only with PAH severity such as increased PVR and intimal thickness, but also with compensated PAH such as lower number of hospitalizations, WHO functional class and NT-proBNP. GWAS integration demonstrated the pink module is enriched for PAH-associated genetic variation in multiple cohorts. Regulatory network analysis revealed that BMPR2 regulates the main target of FDA-approved riociguat, GUCY1A2, in the pink module. Analysis of pathway enrichment and pink hub genes (i.e. ANTXR1 and SFRP4) suggests the pink module inhibits Wnt signaling and epithelial-mesenchymal transition. Cell type deconvolution showed the pink module correlates with higher vascular cell fractions (i.e. myofibroblasts). A pharmacotranscriptomic screen discovered ubiquitin-specific peptidases (USPs) as potential therapeutic targets to mimic the pink module signature. Our multiomics integrative study uncovered a novel gene subnetwork associated with clinicopathologic severity, genetic risk, specific vascular cell types, and new therapeutic targets in PAH. Future studies are warranted to investigate the role and therapeutic potential of the pink module and targeting USPs in PAH.
Gene Expression and Evolution in the Smalltooth Sawfish,Pristis pectinata
Authors: Jarva Taiya M. , Phillips Nicole M. , Eiff Cory Von , Poulakis Gregg R. , Naylor Gavin , Feldheim Kevin A. , Flynt Alex S.
Published: January 2023

Sawfishes (Pristidae) are large, highly threatened rays named for their tooth-studded rostrum, which is used for prey sensing and capture. Of all five species, the smalltooth sawfish,Pristis pectinata, has experienced the greatest decline in range, currently found in only ∼20% of its historic range. To better understand the genetic underpinnings of these taxonomically and morphologically unique animals, we collected transcriptomic data from several tissue types, mapped them to the recently completed reference genome and contrasted the patterns observed with comparable data from other elasmobranchs. Evidence of positive selection was detected in 79 genes inP. pectinata, several of which are involved in growth factor/receptor tyrosine kinase signaling and specification of organ symmetry, suggesting a role in morphogenesis. Data acquired also allow for examination of the molecular components ofP. pectinataelectrosensory systems, which are highly developed in sawfishes and have likely been influential in their evolutionary success.
Change in Monarch Butterfly Winter Abundance Over the Past Decade: A Red List Perspective
Authors: Meehan Timothy D. , Crossley Michael S.
Published: January 2023

1. Assessing invertebrate species for the IUCN Red List under Criterion A requires fitting an appropriate statistical model to available abundance data and calculating a ten-year change (TYC) estimate from predicted abundances. When the rate of change has not been constant across the entire time series, models that accommodate variable change rates are strongly recommended.

2. The monarch butterfly (Danaus plexippus) was recently added to the IUCN Red List (A2ab Endangered) based on analysis of data on winter abundances in Mexico and the western USA between 1993 and 2020. TYC estimates in the monarch assessment came from models that assumed constant change rates. We conducted a Bayesian analysis of the same data using models that accommodated variable change rates and used those models to compute TYC estimates.

3. Our results suggested that monarch population change rates have not been constant. The analysis yielded a model averaged TYC estimate of +5.23%, which was not statistically distinguishable from 0% and was considerably different from values of −46% and −72% in the assessment. The Bayesian posterior probability of a TYC value below −30% (A2ab Vulnerable) was 0.15 and that of a TYC value below −50% (A2ab Endangered) was 0.03.

4. We suggest that a more thorough analysis of recent overwintering abundances will lead to an improved IUCN assessment for monarch butterflies. We recommend that other researchers evaluating monarch conservation status consider using models with variable change rates, as models with constant change rates may not accurately predict the trajectory of monarch abundances into the future.
Testing the accuracy of species distribution models based on community science data
Authors: Velde Mélusine , Cooper Jacob C. , Garrod Holly
Published: January 2023

While traditional methods of tracking species, collecting specimens, and performing surveys are known to be accurate, additional opportunities to broaden the data pool are evolving. Community science data5has emerged as a new way of gathering large amounts of data, but little research has been done on its reliability for making models for novel locations. The goal of this project was to test the reliability of eBird data as the primary dataset for ecological niche modeling by determining the accuracy of models derived from the citizen-science based eBird dataset. I made species distribution models of 676 bird species in Costa Rica based on eBird observations to predict which species would be found in two localities in Costa Rica that were surveyed. I compared the predictions with these field surveys to determine the prediction success and Sorensen index of the models. Overall, I found that while spatio-temporal factors can affect the accuracy of ecological models, eBird data have great potential as data for species distribution modeling. The models more accurately predicted the community composition in the rural locality as opposed to the more urban locality, and the accuracy of the models increased when compared with data that covered two month as opposed to one month time periods. I tested to see how the number of observations per species influenced the predictive ability of the models and determined that an intermediate number of observations led to better models. These are important metrics to understand because modeling can be an informative and cost effective way to monitor inaccessible areas and can be used in conservation efforts.
Computational study ofPiper betleL. phytocompounds byinsilico and ADMETanalysis for prediction of potential xanthine oxidase inhibitory activity
Authors: Chakravarthi P. Vikrama , Karthikeyan M. , Lakshmanan L. , Murugesan S. , Arivuchelvan A. , Sukumar K. , Arulmozhi A. , Jagadeeswaran A.
Published: January 2023

Background

Xanthine oxidase (XO) enzyme is directly associated with pathogenesis of gout and indirectly with cancer, diabetes and metabolic syndromes. Allopurinol is a xanthine oxidase inhibitor which is useful in the treatment of gout but it causes side effects in humans and birds. Therefore, this study sought to identify the alternative compound from the natural resources with fewer side effects than the conventional ones.

Objectives

The present study was designed to findout the xanthine oxidase inhibitory activity ofPiper betlephytocompounds in comparison with Allopurinol.

Methods

The detection of phytocompounds present in theP. betleL. extract was identified through Gas Chromatography Mass Spectrometry (GC-MS) analysis. Theinsilicoanalysis and ADMET properties were evaluated for the GC-MS derivedP.betlephytocompounds. Among the 32 phyto compounds ofP.betle, 18 were showed favourable affinity with xanthine oxidase and their different conformational structures were docked in schrodinger module with xanthine oxidase enzyme structure. The interpretation of results was carried out through GLIDE XP Scoring, GLIDE Energy, MM-GBSA energy and hydrogen bond and Pi-Pi interactions. Further the absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis were also carriedout using QIKPRO programme.

Results

The results revealed that, the twelve phytocompounds ofP.betleshowed GLIDE XP docking score (−6.881 to - 4.766 Kcal/mol) higher than allopurinol (−4.535 Kcal/mol) and 11 phytocompounds showed higher GLIDE energy (−42.822 Kcal/mol to - 36.706 Kcal/mol) than allopurinol (−32.676 Kcal/mol). Chromonol and eugenol were the most potential compounds ofP.betlewhich showed both hydrogen bond and Pi-Pi interactions with the target xanthine oxidase as that of standard drug allopurinol. The selected phytocompounds satisfied the ADME descriptors and have no violation of Lipinski’s rule of five.

Conclusions

Theinsilicoand ADMET profile study on the phytocompounds ofP.betlepredicted their promising potential xanthine oxidase inhibition activity and they could be developed as alternate molecules against synthetic agents byinvivoexperiments for the treatment of xanthine oxidase associated diseases like hyperuricimia and cardiovascular disorders.
Spinal cord injury in mice amplifies anxiety: a novel light-heat conflict test exposes increased salience of anxiety over heat
Authors: Lee Sydney E. , Greenough Emily K. , Fonken Laura K. , Gaudet Andrew D.
Published: January 2023

Spinal cord injury (SCI) predisposes individuals to anxiety and chronic pain. Anxiety- and pain-like behavior after SCI can be tested in rodents, yet commonly used tests assess one variable and may not replicate effects of SCI or sex differences seen in humans. Thus, novel preclinical tests should be optimized to better evaluate behaviors relating to anxiety and pain. Here, we use our newly developed conflict test – the Thermal Increments Dark-Light (TIDAL) test – to explore how SCI affects anxiety- vs. pain-like behavior, and whether sex affects post-SCI behavior. The TIDAL conflict test consists of two plates connected by a walkway; one plate remains illuminated and at an isothermic temperature, whereas the other plate is dark but is heated incrementally to aversive temperatures. Control mice are tested with both plates illuminated (thermal place preference). Female and male mice received moderate T9 contusion SCI or remained uninjured. At 7 days post-operative (dpo), mice with SCI increased dark plate preference throughout the TIDAL conflict test compared to uninjured mice. SCI increased dark plate preference for both sexes, although female (vs. male) mice remained on the heated-dark plate to higher temperatures. Mice with SCI that repeated TIDAL at 7 and 21 dpo showed reduced preference for the dark-heated plate at 21 dpo. Overall, in female and male mice, SCI enhances the salience of anxiety (vs. heat sensitivity). The TIDAL conflict test meets a need for preclinical anxiety- and pain-related tests that recapitulate the human condition; thus, future rodent behavioral studies should incorporate TIDAL or other conflict tests to help understand and treat neurologic disorders.
The MTORC1-AHR pathway sustains translation and autophagy in tumours under tryptophan stress
Authors: Holfelder Pauline , Hensen Lucas , Prentzell Mirja Tamara , Navas Patricia Razquin , Solvay Marie , Sadik Ahmed , Sayeeram Deepak , Rehbein Ulrike , Bausbacher Tobias , Egger Anna-Sophia , Regin Leon , Heberle Alexander M. , Seifert Sophie , Leytens Alexandre , Kowar Alexander , Waltl Lorenz , Gollowitzer André , Kataura Tetsushi , Ouhadi Seema , Karabogdan Ivana , Hotze Madlen , Kipura Tobias , van Pijkeren Alienke , Zhang Yang , Peiris Maria Rodriguez , Barile Cecilia , Zhu Jingjing , Timpen Lea Emmy , Hatzmann Florian , Reintjes Anja , Berdel Bianca , Somarribas Patterson Luis F. , Reil Michèle , Peters Vera , Pittol Jose Ramos , van ˈt Land-Kuper Ineke , Eckhardt Lara E. , Sievers Philipp , Sahm Felix , Mohammed Shad A. , Börding Teresa , Harder Sönke , Loayza-Puch Fabricio , Korolchuk Viktor I. , Schlüter Hartmut , Dengjel Jörn , Koeberle Andreas , Hopf Carsten , Trump Saskia , Kwiatkowski Marcel , Sers Christine , Van den Eynde Benoit J. , Opitz Christiane A. , Thedieck Kathrin
Published: January 2023

Tumours face tryptophan (Trp) depletion, but the mechanisms sustaining protein biosynthesis under Trp stress remain unclear. We report that Trp stress increases the levels of the translation repressor EIF4EBP1. Yet, at the same time, EIF4EBP1 is selectively phosphorylated by the metabolic master regulator MTORC1 kinase, preventing EIF4EBP1 from inhibiting translation. MTORC1 activity under Trp stress is unexpected because the absence of amino acids is typically linked with MTORC1 inhibition. EIF4EBP1-sensitive translation in Trp starved cells is sustained by EGFR and RAS signalling to MTORC1. Via this mechanism, Trp stress enhances the synthesis and activity of the aryl hydrocarbon receptor (AHR). This is noteworthy as Trp catabolites are known to activate AHR, and therefore Trp stress was previously considered to inhibit AHR. Trp stress-induced AHR enhances the expression of key regulators of autophagy, which sustains intracellular Trp levels and Trp-charged tRNAs for translation. Hence, Trp stress switches MTORC1 from its established inhibitory function into an enhancer of autophagy, acting through AHR. The clinical potential of this fundamental mechanism is highlighted by the activity of the mTORC1-AHR pathway and an autophagy signature in 20% of glioblastoma patients, opening up new avenues for cancer therapy.
Ex vivotissue perturbations coupled to single cell RNA-seq reveal multi-lineage cell circuit dynamics in human lung fibrogenesis
Authors: Lang Niklas J. , Gote-Schniering Janine , Porras-Gonzalez Diana , Yang Lin , De Sadeleer Laurens J. , Jentzsch R. Christoph , Shitov Vladimir A. , Zhou Shuhong , Ansari Meshal , Agami Ahmed , Mayr Christoph H. , Kashani Baharak Hooshiar , Chen Yuexin , Heumos Lukas , Pestoni Jeanine C. , Geeraerts Emiel , Anquetil Vincent , Saniere Laurent , Wögrath Melanie , Gerckens Michael , Hatz Rudolf , Kneidinger Nikolaus , Behr Jürgen , Wuyts Wim A. , Stoleriu Mircea-Gabriel , Luecken Malte D. , Theis Fabian J. , Burgstaller Gerald , Schiller Herbert B.
Published: January 2023

Pulmonary fibrosis develops as a consequence of failed regeneration after injury. Analyzing mechanisms of regeneration and fibrogenesis directly in human tissue has been hampered by the lack of organotypic models and analytical techniques. In this work, we coupledex vivocytokine and drug perturbations of human precision-cut lung slices (hPCLS) with scRNAseq and induced a multi-lineage circuit of fibrogenic cell states in hPCLS, which we show to be highly similar to thein vivocell circuit in a multi-cohort lung cell atlas from pulmonary fibrosis patients. Using micro-CT staged patient tissues, we characterized the appearance and interaction of myofibroblasts, an ectopic endothelial cell state and basaloid epithelial cells in the thickened alveolar septum of early-stage lung fibrosis. Induction of these states in theex vivohPCLS model provides evidence that the basaloid cell state was derived from alveolar type-2 cells, whereas the ectopic endothelial cell state emerged from capillary cell plasticity. Cell-cell communication routes in patients were largely conserved in the hPCLS model and anti-fibrotic drug treatments showed highly cell type specific effects. Our work provides an experimental framework for perturbational single cell genomics directly in human lung tissue that enables analysis of tissue homeostasis, regeneration and pathology. We further demonstrate that hPCLS offers novel avenues for scalable, high-resolution drug testing to accelerate anti-fibrotic drug development and translation.
Phosphorylation and Lamin B receptor modulate the accumulation of PERIOD protein foci
Authors: Li Mengna , Li Shujing , Zhang Luoying
Published: January 2023

Circadian clock drives the 24h rhythm in our behavior and physiology. Previously, we have shown that inner nuclear membrane protein Lamin B receptor (LBR) regulates circadian rhythm in human cells andDrosophila, while the underlying mechanism is unclear (Lin et al., 2014). A very recent study reported that the circadian clock protein PERIOD is organized into discrete foci at the nuclear envelope in fly circadian neurons, which is believed to be important for controlling the subcellular localization of clock genes. Loss of LBR leads to disruption of these foci, but how they are regulated is yet unknown. Here we found that LBR likely facilitates PER foci accumulation by destabilizing the catalytic subunit of protein phosphatase 2A, MICROTUBULE STAR (MTS). MTS is known to dephosphorylate PER and hampers the accumulation of PER foci. On the other hand, the circadian kinase DOUBLETIME (DBT) which phosphorylates PER enhances the accumulation of the foci. These foci are likely phase-separated condensates, the formation of which mediated by intrinsically disordered region in PER. Taken together, here we demonstrate a key role for phosphorylation in promoting the accumulation of PER foci, while LBR modulates this process by impinging on the circadian phosphatase MTS.
Arp2/3 Complex Activity Enables Nuclear YAP for Naïve Pluripotency of Human Embryonic Stem Cells
Authors: Meyer Nathaniel P. , Singh Tania , Kutys Matthew L. , Nystul Todd , Barber Diane L.
Published: January 2023

Our understanding of transitions of human embryonic stem cells between distinct stages of pluripotency relies predominantly on regulation by transcriptional and epigenetic programs with limited insight on the role of established morphological changes. We report remodeling of the actin cytoskeleton of human embryonic stem cells (hESCs) as they transition from primed to naïve pluripotency that includes assembly of a ring of contractile actin filaments encapsulating colonies of naïve hESCs. Activity of the Arp2/3 complex is required for the actin ring, uniform cell mechanics within naïve colonies, nuclear translocation of the Hippo pathway effectors YAP and TAZ, and effective transition to naïve pluripotency. RNA-sequencing analysis confirms that Arp2/3 complex activity regulates Hippo signaling in hESCs, and impaired naïve pluripotency with inhibited Arp2/3 complex activity is rescued by expressing a constitutively active, nuclear-localized YAP-S127A. These new findings on the cell biology of hESCs reveal a mechanism for cytoskeletal dynamics coordinating cell mechanics to regulate gene expression and facilitate transitions between pluripotency states.
A method for pole figure measurements via a dynamic segmented spiral scheme
Authors: Chandramouleeswaran Surya , Creuziger Adam , Findley Kip
Published: January 2023

A new method for pole figure measurement is described, entitled a dynamic segmented spiral scheme. Compared with the schemes currently in use, the dynamically segmented spiral scheme is shown to have advantages in terms of evenness of pole figure coverage and phase fraction accuracy. The phase fraction accuracy is shown to be robust for a variety of texture components commonly encountered in steels and for texture sharpness exceeding what is commonly encountered for rolled sheet steels. This scheme provides a promising alternative to conventional methods of simultaneous texture and phase fraction measurement.
Form factor of any polyhedron and its singularities derived from a projection method
Authors: Yang Tianjuan , Chen Xiuguo , Zhang Jiahao , Ma Jianyuan , Liu Shiyuan
Published: January 2023

An analytical and general form factor for any polyhedron is derived on the basis of a projection method, in terms of the vertex coordinates and topology of the polyhedron. An integral over the polyhedron equals the sum of the signed integrals over a set of dissected tetrahedra by defining a sign function, and a general tetrahedral form factor is established by defining a projection method. All possible singularities present in the formula are discussed in detail. Using a MATLAB implementation, illustrative examples are discussed to verify the accuracy and generality of the method. The use of the scalar product operation and the sign function in this work allows a general and neat formula to be obtained for any polyhedron, including convex and concave polyhedra. The formulas and discussions presented here will be useful for the characterization of nanoparticles using small-angle scattering techniques.
A spherical harmonics method for processing anisotropic X-ray atomic pair distribution functions
Authors: Zhang Guanjie , Liu Hui , Chen Jun , Lin He , Zhang Nan
Published: January 2023

In this work, a general spherical harmonics method for the extraction of anisotropic pair distribution functions (PDFs) is described. In the structural study of functional crystallized materials, there is an urgent need for investigation of local structures under the application of external stimuli, such as an electric field and stress. A well established technique for local structural studies is PDF analysis, but the extraction of X-ray PDF data is usually based on angular integrations of isotropic X-ray structure functions, which is no longer valid for the anisotropic responses of materials under orientation-dependent stimuli. Therefore, an advanced spherical harmonics method has been developed, to transform 2D X-ray total-scattering data into anisotropic PDF data on the basis of the 3D diffraction geometry and a Fourier transform. The electric-field-induced local structural change in PbZr0.54Ti0.46O3 ceramics is presented to demonstrate the effectiveness of this method.
Synthesis and topology analysis of chloridotriphenyl(triphenyl phosphate-κO)tin(IV)
Authors: Pouye Serigne Fallou , Bernès Sylvain , Yaffa Lamine , Diallo Waly , Cissé Ibrahima , Diop Cheikh Abdoul Khadir , Sidibé Mamadou , Diop Libasse
Published: January 2023

The title SnIV complex, [Sn(C6H5)3Cl(C18H15O4P)], is a formal adduct between triphenyl phosphate (PhO)3P=O and the stannane derivative chloridotriphenyltin, SnPh3Cl. The structure refinement reveals that this molecule displays the largest Sn—O bond length for compounds including the X=O→SnPh3Cl fragment (X = P, S, C, or V), 2.6644 (17) Å. However, an AIM topology analysis based on the wavefunction calculated from the refined X-ray structure shows the presence of a bond critical point (3,−1), lying on the interbasin surface separating the coordinated phosphate O atom and the Sn atom. This study thus shows that an actual polar covalent bond is formed between (PhO)3P=O and SnPh3Cl moieties.
Crystal structure of barium dinickel(II) iron(III) tris[orthophosphate(V)], BaNi2Fe(PO4)3
Authors: Ouaatta Said , Bouraima Adam , Benhsina Elhassan , Khmiyas Jamal , Assani Abderrazzak , Saadi Mohamed , El Ammari Lahcen
Published: January 2023

The orthophosphate BaNi2Fe(PO4)3 has been synthesized by a solid-state reaction route and characterized by single-crystal X-ray diffraction and energy-dispersive X-ray spectroscopy. The crystal structure comprises (100) sheets made up of [Ni2O10] dimers that are linked to two PO4 tetrahedra via common edges and vertices and of linear infinite [010] chains of corner-sharing [FeO6] octahedra and [PO4] tetrahedra. The linkage of the sheets and chains into a framework is accomplished through common vertices of PO4 tetrahedra and [FeO6] octahedra. The framework is perforated by channels in which positionally disordered Ba2+ cations are located.
2,5-Bis[5-(3,5-didodecyloxyphenyl)-1,3,4-oxadiazol-2-yl]-3,6-dimethylpyrazine
Authors: Joa Benedikt , Schollmeyer Dieter , Detert Heiner
Published: January 2023

The nearly planar molecule of the title compound, C70H112N6O6, is centrosymmetric with two all-s-trans chains, the other two chains have an s-cis unit starting with the oxygen atoms. The chains are interdigitated in the packing.
Research on static fault tree analysis method for inerting system safety based on random number generation
Authors: Zhang Ruihua , Geng Leiming , Liu Weihua
Published: January 2023

Purpose

To reduce the flammability exposure assessment time and meet the requirements of airworthiness regulations of transport aircraft, inerting system has become the standard configuration of modern civil aircraft. Therefore, airworthiness regulations put forward definite quantitative index requirements for the safety of inerting system, and to obtain the quantitative data of the safety of inerting system, it is necessary to solve the calculation method. As one of the quantitative/qualitative evaluation techniques for system safety, fault tree analysis is recognized by international airworthiness organizations and national airworthiness certification agencies. When fault tree analysis technology is applied to quantitative analysis of the safety of inerted system, there are still some problems, such as heavy margin of constructing fault tree, great difficulty, high requirement for analysts and poor accuracy of solving when there are too many minimum cut sets. However, based on tens of thousands of flight simulation tests, Monte Carlo random number generation method can solve this problem.

Design/methodology/approach

In this paper, the fault tree of airborne inerting system is established, and the top event is airborne inerting system losing air separation function. Monte Carlo method based on random number generation is used to carry out system security analysis. The reliability of this method is verified.

Findings

The static fault tree analysis method based on Monte Carlo random number generation can not only solve the problem of quantitative analysis of inerting system, but can also avoid the defects of complicated solution and inaccurate solution caused by the large number of minimum cut sets, and its calculation results have good reliability.

Practical implications

The research results of this paper can be used as supporting evidence for airworthiness compliance of airborne inerting system.

Originality/value

The research results of this paper can provide practical guidance for the current civil airworthiness certification work.
Investigating the experience of professional carers supporting individuals with intellectual disability who were at risk of admission – a qualitative study
Authors: Manandhar-Richardson Mizla , Woodrow Ceri , Cooper-Taylor Georgia
Published: January 2023

Purpose

This study aims to understand the experiences of professional paid carers providing community support to people with intellectual disability “at risk of admission”. This study explores factors that were helpful or lacking in terms of the support the carers received from NHS health services during this time.

Design/methodology/approach

This study conducted semi-structured interview with eight participants. Thematic analysis was used to analyse the data.

Findings

Three main themes and ten subthemes were identified. The first main theme was “support systems” that were available or lacking for the client and their carers. The second main theme was “training and supervision” available to the carers and their team when the individual they supported needed additional support. The third theme was “change” clients encountered which included changes in the environment as well as changes because of COVID-19 pandemic.

Originality/value

To the best of the authors’ knowledge, this is the first study on experiences of carers during specifically high stress periods, such as when the clients they are supporting are at risk of hospital admission.
The assurance providers’ role in improving the independent assurance statement quality on sustainability reporting
Authors: Harindahyani Senny , Agustia Dian
Published: January 2023

Purpose

This study aims to investigate the effect of assurance provider types on the independent assurance statement quality of Asian companies' sustainability report (SR) and examine environmental risk’s role as a moderating variable.

Design/methodology/approach

This study analyzes large Asian companies' stand-alone SR using moderated regression analysis to test hypotheses. Textual analysis is conducted to identify environmental risk disclosures.

Findings

This study shows that accounting assurance providers affect independent assurance statement quality in terms of compliance with assurance statement elements, while nonaccounting assurance providers can better accommodate environmental risk information required by the intended users.

Research limitations/implications

This study has several limitations. The research focuses on assurance statements and stand-alone SR of large companies in Asia; therefore, future research could examine similar analyses using integrated reports from Asia to investigate whether the results will differ. Additionally, this study does not divide assurance providers into Big-N and non-Big-N; thereby, it can be extended in future research.

Practical implications

Assurance providers need to consider environmental risk as a critical issue for the intended users to issue a high-quality independent assurance statement.

Social implications

Assurance statements issued by assurance providers increase public confidence in the reliability of the information contained in the SR. Therefore, regulators are expected to immediately set mandatory standards for sustainability assurance practices.

Originality/value

This study proves that accounting assurance providers can improve assurance statement quality. The variable environmental risk is also proven to be a pure moderator in negatively interacting the effect of assurance provider types on independent assurance statement quality.