bluuebunny/crossref_metadata_2025 huggingface dataset:
ULTRA-WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN MILD FAMILIAL EXUDATIVE VITREORETINOPATHY
Authors: Wang You , Lai Yanting , Zhou Xiaodi , Zhang Ting , Sun Limei , Zhang Zhaotian , Huang Li , Li Songshan , Ding Xiaoyan
Published: February 2023

Purpose:

To investigate ultra-widefield optical coherence tomography angiography (UWF-OCTA) to detect and evaluate mild familial exudative vitreoretinopathy and compare the detective ratio of UWF-OCTA with ultra-widefield scanning laser ophthalmoscopy and ultra-widefield fluorescein angiography.

Methods:

The patients with familial exudative vitreoretinopathy were included in this study. UWF-OCTA, using a 24- × 20-mm montage, was performed for all patients. All images were independently tested for the presence of familial exudative vitreoretinopathy-associated lesions. Statistical analysis was performed with SPSS V.24.0.

Results:

Forty-six eyes of 26 participants were included in the study. Ultra-widefield optical coherence tomography angiography was found to be greatly superior to ultra-widefield scanning laser ophthalmoscopy in detecting peripheral retinal vascular abnormality (P < 0.001) and peripheral retinal avascular zone (P < 0.001). The detection rates of peripheral retinal vascular abnormality, peripheral retinal avascular zone, retinal neovascularization, macular ectopia, and temporal midperipheral vitreoretinal interface abnormality were comparable with ultra-widefield fluorescein angiography images (P > 0.05). Furthermore, vitreoretinal traction (17/46, 37%) and small foveal avascular zone (17/46, 37%) were detected effectively on UWF-OCTA.

Conclusion:

Ultra-widefield optical coherence tomography angiography is a reliable noninvasive tool to detect familial exudative vitreoretinopathy lesions, especially in mild patients or asymptomatic family members. The unique manifestation of UWF-OCTA offers an alternative to ultra-widefield fluorescein angiography for the screening and diagnosis of FEVR.
Sickness Presenteeism and Psychosocial Risk Factors According to Inequality Axes
Authors: Gómez-Domínguez Angela , Ferrer-Rosende Pedro , Esteve-Matalí Laura , Salas-Nicás Sergio , Navarro-Giné Albert
Published: February 2023

Objective

To assess the association between psychosocial risk factors (PSRs) and sickness presenteeism (SP) and examine possible differences according to the major axes of inequality in the labor market. Methods: Cross-sectional study based on a representative sample of the Spanish salaried population. Results: Although nearly all PSR show crude associations with SP, when adjusted for every other PSR, only the workers exposed to lack of role clarity (adjusted prevalence ratio [aPR], 1.30; 95% confidence interval [CI], 1.01 to 1.68), having role conflicts (aPR, 1.45; 95% CI, 1.19 to 1.77) and lack of sense of community at work (aPR, 1.30; 95% CI, 1.06 to 1.59) show a significant association. Conclusions: After adjusting for all PSR, those significantly associated to SP belong to the interpersonal relationships domain. Some of the PSR effects change according to the segmentation axes analyzed.
Non-neonatal Men with Rare Testicular Torsion: A Case Series
Authors: O'Driscoll Kieran M. , Narula Samir , Chu Julianne L. , Best Natalie M. , Vemulapalli Pratibha , Gilchrist Brian F.
Published: February 2023

Testicular torsion involves the testicle twisting which results in an infarcted testis. Emergency surgery is required to salvage the affected testis. There are 2 anatomic pathologies associated with testicular torsion: intravaginal testicular torsion and extravaginal testicular torsion (ETT). Extravaginal testicular torsion is seen perinatally and in neonates; beyond this period, ETT is regarded as exceptionally rare. This case series presents 7 cases of ETT seen in men aged 14 to 20 years. This is the largest and oldest group of patients seen with this pathology. These cases were defined by a pediatric surgeon in an inner city hospital in New York. Two patients' testes were not viable at the time of presentation, and the time of onset to presentation ranged from 30 minutes to 11 hours. Each of these cases had an orchiopexy concomitantly of the contralateral testis. This case series poses key questions regarding the etiology of ETT and the surgical management of such cases.
Anatomically guided reconstruction improves lesion quantitation and detectability in bone SPECT/CT
Authors: Vuohijoki Hanna E. , Constable Christopher J. , Sohlberg Antti O.
Published: February 2023

Bone single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging suffers from poor spatial resolution, but the image quality can be improved during SPECT reconstruction by using anatomical information derived from CT imaging. The purpose of this work was to compare two different anatomically guided SPECT reconstruction methods to ordered subsets expectation maximization (OSEM) which is the most commonly used reconstruction method in nuclear medicine. The comparison was done in terms of lesion quantitation and lesion detectability. Anatomically guided Bayesian reconstruction (AMAP) and kernelized ordered subset expectation maximization (KEM) algorithms were implemented and compared against OSEM. Artificial lesions with a wide range of lesion-to-background contrasts were added to normal bone SPECT/CT studies. The quantitative accuracy was assessed by the error in lesion standardized uptake values and lesion detectability by the area under the receiver operating characteristic curve generated by a non-prewhitening matched filter. AMAP and KEM provided significantly better quantitative accuracy than OSEM at all contrast levels. Accuracy was the highest when SPECT lesions were matched to a lesion on CT. Correspondingly, AMAP and KEM also had significantly better lesion detectability than OSEM at all contrast levels and reconstructions with matching CT lesions performed the best. Quantitative differences between AMAP and KEM algorithms were minor. Visually AMAP and KEM images looked similar. Anatomically guided reconstruction improves lesion quantitation and detectability markedly compared to OSEM. Differences between AMAP and KEM algorithms were small and thus probably clinically insignificant.
Circular RNA circ_0099188 contributes to lipopolysaccharide (LPS)-induced HPAEpiC cell injury by targeting the miR-1236-3p/HMGB3 axis
Authors: Lin Yuhang , Zeng Zhitao , Pan Kechuan
Published: February 2023

Purpose

This study is designed to explore the role and mechanism of circ_0099188 in LPS-engendered HPAEpiC cells.

Methods

Circ_0099188, microRNA-1236-3p (miR-1236-3p), and High mobility group box 3 (HMGB3) levels were measured using real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were assessed using Cell Counting Kit-8 (CCK-8) and flow cytometry assays. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), cleaved-caspase 3, cleaved-caspase 9, and HMGB3 were determined using western blot assay. Interleukin-6 (IL-6), IL-8, IL-1β, and tumor necrosis factor α (TNF-α) levels were analyzed using Enzyme-linked immunosorbent assays (ELISA). After predicting using Circinteractome and Targetscan, the binding between miR-1236-3p and circ_0099188 or HMGB3 was verified using a dual-luciferase reporter, RNA Immunoprecipitation (RIP), and RNA pull-down assays.

Results

Circ_0099188 and HMGB3 were highly expressed, and miR-1236-3p was decreased in LPS-stimulated HPAEpiC cells. Also, the downregulation of circ_0099188 might overturn LPS-triggered HPAEpiC cell proliferation, apoptosis, and inflammatory response. Mechanically, circ_0099188 is able to affect HMGB3 expression by sponging miR-1236-3p.

Conclusion

Circ_0099188 knockdown might mitigate LPS-induced HPAEpiC cell injury by targeting the miR-1236-3p/HMGB3 axis, providing an underlying therapeutic strategy for pneumonia treatment.
Incidence of multiple organ failure in adult polytrauma patients: A systematic review and meta-analysis
Authors: Ting Ryan S. , Lewis Daniel P. , Yang Kevin X. , Nguyen Tam Anh , Sarrami Pooria , Daniel Lovana , Hourigan Samuel , King Kate , Lassen Christine , Sarrami Mahsa , Ridley William , Alkhouri Hatem , Dinh Michael , Balogh Zsolt J.
Published: February 2023

BACKGROUND

Postinjury multiple organ failure (MOF) is the leading cause of late death in trauma patients. Although MOF was first described 50 years ago, its definition, epidemiology, and change in incidence over time are poorly understood. We aimed to describe the incidence of MOF in the context of different MOF definitions, study inclusion criteria, and its change over time.

METHODS

Cochrane Library, EMBASE, MEDLINE, PubMed, and Web of Science databases were searched for articles published between 1977 and 2022 in English and German. Random-effects meta-analysis was performed when applicable.

RESULTS

The search returned 11,440 results, of which 842 full-text articles were screened. Multiple organ failure incidence was reported in 284 studies that used 11 unique inclusion criteria and 40 MOF definitions. One hundred six studies published from 1992 to 2022 were included. Weighted MOF incidence by publication year fluctuated from 11% to 56% without significant decrease over time. Multiple organ failure was defined using four scoring systems (Denver, Goris, Marshall, Sequential Organ Failure Assessment [SOFA]) and 10 different cutoff values. Overall, 351,942 trauma patients were included, of whom 82,971 (24%) developed MOF. The weighted incidences of MOF from meta-analysis of 30 eligible studies were as follows: 14.7% (95% confidence interval [CI], 12.1–17.2%) in Denver score >3, 12.7% (95% CI, 9.3–16.1%) in Denver score >3 with blunt injuries only, 28.6% (95% CI, 12–45.1%) in Denver score >8, 25.6% (95% CI, 10.4–40.7%) in Goris score >4, 29.9% (95% CI, 14.9–45%) in Marshall score >5, 20.3% (95% CI, 9.4–31.2%) in Marshall score >5 with blunt injuries only, 38.6% (95% CI, 33–44.3%) in SOFA score >3, 55.1% (95% CI, 49.7–60.5%) in SOFA score >3 with blunt injuries only, and 34.8% (95% CI, 28.7–40.8%) in SOFA score >5.

CONCLUSION

The incidence of postinjury MOF varies largely because of lack of a consensus definition and study population. Until an international consensus is reached, further research will be hindered.

LEVEL OF EVIDENCE

Systematic Review and Meta-analysis; Level III.
Poor sleep quality, insomnia, and short sleep duration before infection predict long-term symptoms after COVID-19
Authors: Salfi Federico , Amicucci Giulia , Corigliano Domenico , Viselli Lorenzo , D’Atri Aurora , Tempesta Daniela , Ferrara Michele
Published: February 2023

Study objectives

Millions of COVID-19 survivors experience a wide range of long-term symptoms after acute infection, giving rise to serious public health concerns. To date, few risk factors for post-COVID-19 conditions have been determined. This study evaluated the role of pre-infection sleep quality/duration and insomnia severity in the incidence of long-term symptoms after COVID-19.

Methods

This prospective study involved two assessments (April 2020 and 2022). At baseline, sleep quality/duration and insomnia symptoms in participants without current/prior SARS-CoV-2 infection were measured using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). At follow-up, we evaluated the presence of twenty-one symptoms (psychiatric, neurological, cognitive, bodily, and respiratory) one month (n=713, infection in April 2020–February 2022) and three months after COVID-19 (n=333, infection in April 2020–December 2021). Zero-inflated negative binomial models were used to estimate the effect of previous sleep on the number of long-term symptoms. Binomial logistic regressions were performed to evaluate the association between sleep outcomes and the incidence of each post-COVID-19 symptom.

Results

Analyses highlighted a significant effect of pre-infection sleep on the number of symptoms one/three months after COVID-19. Previous higher PSQI and ISI scores, and shorter sleep duration significantly increased the risk of almost every long-term symptom at one/three months from COVID-19.

Conclusion

This study suggested a prospective dose-dependent association between pre-infection sleep quality/quantity and insomnia severity with the manifestation of post-COVID-19 symptoms. Promoting sleep health may represent an effective preventive approach to mitigate the COVID-19 sequelae, with substantial public health and societal implications.

Statement of significance

Determining potential risk factors of long COVID is crucial to driving preventive interventions amongst vulnerable populations. The present study is the first to provide insights into the role of pre-infection sleep disturbances in the occurrence of post-COVID-19 conditions. We demonstrated a strong association between previous sleep quality/duration and insomnia severity with the incidence of a broad spectrum of long-term symptoms one and three months after COVID-19. These results may have large-scale implications, considering the alarming rates of both sleep disturbances and post-COVID-19 manifestations worldwide. Further research is warranted to determine the biobehavioral mechanisms involved. Future studies should also evaluate whether treating sleep problems may improve the subsequent long-term consequences of COVID-19.
Stochastic dynamics of ecological populations subjected to environmental perturbations
Authors: Rezaee Sayeh , Nieto Cesar , Vahdat Zahra , Singh Abhyudai
Published: February 2023

The stochastic logistic model is widely used to capture random fluctuations arising from birth-death processes in ecological populations. We use this model to study the impact of environmental perturbations that may occur naturally or as a consequence of population harvesting. In our model formulation, environmental perturbations occur randomly as per a Poisson process, and the perturbations result in each individual dying with a certain probability of death. Moment closure schemes are employed to derive expressions for the mean and variability in population numbers. Moreover, to quantify the impact of population extinction in our model we compute the probability of extinction using the Finite State Projection (FSP) numerical method. Our analysis shows that rare environmental perturbations with a high probability of death lead to overall larger random fluctuations and extinction risk as compared to frequent perturbations with a low probability of death. Finally, we formulate the problem in the context of population harvesting to find the optimal harvesting rate that maximizes the cumulative yield.
Predicting vertical and shear ground reaction forces during walking and jogging using wearable plantar pressure insoles
Authors: Hajizadeh Maryam , Clouthier Allison L. , Kendall Marshall , Graham Ryan B.
Published: February 2023

Background

The development of plantar pressure insoles has made them a potential replacement for force plates. These wearable devices can measure multiple steps and might be used outside of the lab environment for rehabilitation and evaluation of sport performance. However, they can only measure the normal force which does not completely represent the vertical ground reaction force (GRF). In addition, they are not able to measure shear forces which play an import role in the dynamic performance of individuals. Indirect approaches might be implemented to improve the accuracy of the force estimated by plantar pressure systems.

Research question

The aim of this study was to predict the vertical and shear components of ground reaction force from plantar pressure data using recurrent neural networks.

Methods

GRF and plantar pressure data were collected from sixteen healthy individuals during 10 trials of walking and five trials of jogging using Bertec force plates and FScan plantar pressure insoles. A long short-term memory (LSTM) neural network was built to consider the time dependency of pressure and force data in predictions. The data were split into three subsets of train, to train the LSTM model, evaluate, to optimize the model hyperparameters, and test sets, to assess the accuracy of the model predictions.

Results

The results of this study showed that our LSTM model could accurately predict the shear and vertical GRF components during walking and jogging. The predictions were more accurate during walking compared to jogging. In addition, the predictions of mediolateral force had higher error and lower correlation compared to vertical and anteroposterior components.

Significance

The LSTM model developed in this study may be an acceptable option for accurate estimation of GRF during outdoor activities which can have significant impacts in rehabilitation, sport performance, and gaming.
Hidden changes to prespecified primary outcomes of clinical trials completed between 2009 and 2017 in German University Medical Centres: A meta-research study
Authors: Holst Martin R. , Haslberger Martin , Yerunkar Samruddhi , Strech Daniel , Hemkens Lars G. , Carlisle Benjamin G.
Published: February 2023

Objectives

To assess how often clinical trials exhibit primary outcome discrepancies within registry records that would not be caught by comparing results publications to the latest registry entry, but would require analysing the registration history.

Design

Meta-research study.

Setting

All 1746 randomised clinical trials with published results, registered inClinicalTrials.govor Deutsches Register Klinischer Studien (DRKS), completed at German University Medical Centres between 2009 and 2017. We analysed registry entries for all trials and publications for a random sample of 292 trials.

Participants

Not applicable.

Interventions

Not applicable.

Main outcome measures

[1] Primary outcome discrepancies between registry entries at key study milestones and [2] the first results publication. [3] ‘Hidden’ discrepancies, i.e., only reported in the registry before the last entry, meaning they would only be detected by assessing the full registry change history. We considered discrepancies major if primary outcomes were newly added, dropped, or changed to or from secondary outcomes. [4] Proportion of publications transparently reporting discrepancies. [5] Characteristics associated with ‘open’ and ‘hidden’ discrepancies.

Results

Of all 1746 trials, 23% (n=393) had primary outcome discrepancies between trial start and latest registry entry, with 8% (n=142) being major. Primary outcomes in publications were different from the latest registry entry in 41% of trials (120 of the 292 sampled trials; 95% CI [35%, 47%]), with major discrepancies in 18% (54 of 292; 95% CI [14%, 23%]). ‘Hidden’ discrepancies were observed in 14% of trials (41/292; 95% CI [10%, 19%]). Only 1% of discrepancies were reported in the publications (2/161, 95% CI [0%, 4%]). Trials were more likely to have a within-registry discrepancy if they had an earlier registration year (OR 0.74; 95% CI [0.69, 0.80]), were registered onClinicalTrials.gov(OR 0.41; 95% CI [0.23, 0.70]), or had been industry-sponsored (OR 0.29; 95% CI [0.21, 0.41]).

Conclusions

Changes to primary trial outcomes are common, often have major relevance, are rarely transparently reported and typically not detectable with an inspection of the latest registry entry. Authors need to be more transparent and registry entries of published trials need to require more in-depth analysis to reveal potentially misleading reporting practices.

Protocol registration

Open Science Framework (https://osf.io/t3qva; amendment inhttps://osf.io/qtd2b).
DeepHeme: A generalizable, bone marrow classifier with hematopathologist-level performance
Authors: Goldgof Gregory M. , Sun Shenghuan , Van Cleave Jacob , Wang Linlin , Lucas Fabienne , Brown Laura , Spector Jacob D. , Boiocchi Leonardo , Baik Jeeyeon , Zhu Menglei , Ardon Orly , Lu Chuanyi M. , Dogan Ahmet , Goldgof Dmitry B. , Carmichael Iain , Prakash Sonam , Butte Atul J.
Published: February 2023

Morphology-based classification of cells in the bone marrow aspirate (BMA) is a key step in the diagnosis and management of hematologic malignancies. However, it is time-intensive and must be performed by expert hematopathologists and laboratory professionals. We curated a large, high-quality dataset of 41,595 hematopathologist consensus-annotated single-cell images extracted from BMA whole slide images (WSIs) containing 23 morphologic classes from the clinical archives of the University of California, San Francisco. We trained a convolutional neural network, DeepHeme, to classify images in this dataset, achieving a mean area under the curve (AUC) of 0.99. DeepHeme was then externally validated on WSIs from Memorial Sloan Kettering Cancer Center, with a similar AUC of 0.98, demonstrating robust generalization. When compared to individual hematopathologists from three different top academic medical centers, the algorithm outperformed all three. Finally, DeepHeme reliably identified cell states such as mitosis, paving the way for image-based quantification of mitotic index in a cell-specific manner, which may have important clinical applications.
Functional antagonistic interactions and genomic insights into the biosynthetic potential of human gut-derived microbiota
Authors: Hussain Aehtesham , Patwekar Umera , Mongad Dattatray S , Nimonkar Yogesh , Mundhe Swapnil , Paul Dhiraj , Prakash Om , Shouche Yogesh S
Published: February 2023

Concerning the biological interactions within the gut microbiome, the specialized small molecules encoded by commensal microbes mediate distinct functional aspects. However, the landscape of antagonistic interactions mediated by specialized strains and their small molecules broadly remains. Here, we sought to evaluate antimicrobial interactions as a defensive contributor to gain new insights into structure-related functions or to bring the therapeutic potential of derived molecules. We elucidated the antagonistic landscape within a collection of 330 human-gut-derived commensal microbial strains cultivated from healthy human subjects. We characterized potential antagonistic strains and found a strain-specific selective inhibition contrary to common antimicrobial drugs that wipe out a broad range of species usually found in environmental microbes. Using functional and genomic approaches for accessing biologically active natural product molecules, we identified significant biosynthetic gene clusters (BGCs) encoding the important compound families in representative gut strains which contribute to antagonistic activities and are important in host defense or maintaining homeostasis in the gut. The subsets of the BGCs were represented in metagenomics sequencing data from healthy individuals. The cell culture secretome of strains revealed potential biomarkers linked to hallmark pathways. Together, these microorganisms encode biosynthetic novelty and represent a source of biologically significant natural products important in developing new treatments for infectious diseases to cut the usage of broad-spectrum antibiotics and represent a way to combat antimicrobial resistance. Consortia of such strains can be utilized as an option for precise editing of the microbiomes or fine-tuning the microbiota-modulating therapies.
A new competitive strategy to unveil the antibiotic-producing Actinobacteria
Authors: Hussain Aehtesham , Patwekar Umera , Majumder Anirban , Majeed Aasif , Shouche Yogesh S
Published: February 2023

The bacterial phylum Actinobacteria encompasses microorganisms with incomparable metabolic versatility and deep resource of medicines. However, the recent decrease in the discovery rate of antibiotics warrants innovative strategies to harness actinobacterial resources for lead discovery. Indeed, microbial culturing efforts measuring the outcomes of specific genera lagged behind the detected microbial potential. Herein, we used a distinct competitive strategy that exploits competitive microbial interactions to accelerate the diversification of strain libraries producing antibiotics. This directed-evolution-based strategy shifted the diversity of Actinobacteria over the experimental time course (0-8 days) and led to the isolation of Actinobacterial strains with distinct antimicrobial spectrum against pathogens. To understand the competitive interactions over experimental time, the metagenomic community sequencing revealed that actinobacterial members from familiesNocardiaceaeandCellulomonadaceaewith relatively increased abundances towards end, are thus competitively advantageous. Whilst comparing the Actinobacteria retrieved in the competitive strategy to that of the routinely used isolation method, the Actinobacteria genera identified from competitive communities differed relatively in abundances as well as antimicrobial spectrum compared to actinobacterial strains retrieved in classical method. In sum, we present a strategy that influences microbial interactions to accelerate the likelihood of potential actinobacterial strains with antimicrobial potencies.
Towards estimating marine wildlife abundance using aerial surveys and deep learning with hierarchical classifications subject to error
Authors: Augustine Ben C. , Koneff Mark D. , Pickens Bradley A. , Royle J. Andrew
Published: February 2023

Aerial count surveys of wildlife populations are a prominent monitoring method for many wildlife species. Traditionally, these surveys utilize human observers to detect, count, and classify observations to species. However, given recent technological advances, many research groups are exploring the combined use of remote sensing and deep learning methods to replace human observers in order to improve data quality and reproducibility, reduce disturbance to wildlife, and increase aircrew safety. Given that deep learning detection and classification are not perfect and that statistical inference from ecological models is generally very sensitive to misclassification, we require study designs and statistical models to accommodate these observation errors.

As part of an ongoing effort by the U.S. Fish and Wildlife Service, Bureau of Ocean Energy Management, and U.S. Geological Survey to survey marine birds and other marine wildlife using digital aerial imagery and deep learning object detection and classification, we developed a general hierarchical model for estimating species-specific abundance that accommodates object-level errors in classification. We consider hierarchical deep learning classification at multiple taxonomic levels subject to misclassification, hierarchically-structured human validation data subject to partial and erroneous misclassification, and an image censoring process leading to preferential sampling. We demonstrate that this model can estimate species-specific abundance and habitat relationships without bias when the assumptions are met, and we discuss the plausibility of these assumptions in practice for this study and others like it.

Finally, we use this model to demonstrate the relevance of the features of the ecological systems under study to the classification task itself. In models that couple the ecological and classification processes into a single, hierarchical model, the true classes are treated as latent variables to be estimated and are informed by both the classification probability parameters and the ecological parameters that determine the expected frequencies of each class at the level the data are being modeled (e.g., site or site by occasion). We show that ignoring the expected frequencies of each class (when they are imbalanced) can cause correction for misclassification to produce biased parameter estimates, but coupling the ecological and classification models allows for the variability in relative class frequency across space and time due to ecological and sampling conditions to be accommodated with spatial or temporal covariates. As a result, bias is removed, classification is more accurate, and uncertainty is propagated between the ecological and classification models. We therefore argue that ability of deep learning classifiers, and classifiers more generally, to produce reliable ecological inference depends, in part, on the ecological system under study.
Kinetic networks identify TWIST2 as a key regulatory node in adipogenesis
Authors: Dutta Arun B. , Lank Daniel S. , Przanowska Roza K. , Przanowski Piotr , Wang Lixin , Nguyen Bao , Walavalkar Ninad M. , Duarte Fabiana M. , Guertin Michael J.
Published: February 2023

Adipocytes contribute to metabolic disorders such as obesity, diabetes, and atherosclerosis. Prior characterizations of the transcriptional network driving adipogenesis have overlooked transiently acting transcription factors (TFs), genes, and regulatory elements that are essential for proper differentiation. Moreover, traditional gene regulatory networks provide neither mechanistic details about individual regulatory element–gene relationships nor temporal information needed to define a regulatory hierarchy that prioritizes key regulatory factors. To address these shortcomings, we integrate kinetic chromatin accessibility (ATAC-seq) and nascent transcription (PRO-seq) data to generate temporally resolved networks that describe TF binding events and resultant effects on target gene expression. Our data indicate which TF families cooperate with and antagonize each other to regulate adipogenesis. Compartment modeling of RNA polymerase density quantifies how individual TFs mechanistically contribute to distinct steps in transcription. The glucocorticoid receptor activates transcription by inducing RNA polymerase pause release, whereas SP and AP-1 factors affect RNA polymerase initiation. We identifyTwist2as a previously unappreciated effector of adipocyte differentiation. We find that TWIST2 acts as a negative regulator of 3T3-L1 and primary preadipocyte differentiation. We confirm thatTwist2knockout mice have compromised lipid storage within subcutaneous and brown adipose tissue. Previous phenotyping ofTwist2knockout mice and Setleis syndromeTwist2−/−patients noted deficiencies in subcutaneous adipose tissue. This network inference framework is a powerful and general approach for interpreting complex biological phenomena and can be applied to a wide range of cellular processes.
Reducing environmentally mediated transmission to moderate impacts of an emerging wildlife disease
Authors: Hoyt Joseph R. , Parise Katy L. , DePue John E. , Kaarakka Heather M. , Redell Jennifer A. , Scullon William H. , O'Reskie Rich , Foster Jeffrey T. , Kilpatrick A. Marm , Langwig Kate E. , White J. Paul
Published: February 2023

Emerging infectious diseases have caused population declines and biodiversity loss. The ability of pathogens to survive in the environment, independent of their host, can exacerbate disease impacts and increase the likelihood of species extinction. Control of pathogens with environmental stages remains a significant challenge for conservation and effective management strategies are urgently needed.

We examined the effectiveness of managing environmental exposure to reduce the impacts of an emerging infectious disease of bats, white‐nose syndrome (WNS). We used a chemical disinfectant, chlorine dioxide (ClO2), to experimentally reduce Pseudogymnoascus destructans, the fungal pathogen causing WNS, in the environment. We combined laboratory experiments with 3 years of field trials at four abandoned mines to determine whether ClO2 could effectively remove P. destructans from the environment, reduce host infection and limit population impacts.

ClO2 was effective at killing P. destructans in vitro across multiple concentrations. In field settings, higher concentrations of ClO2 treatment were needed to sufficiently reduce viable P. destructans conidia in the environment.

The reduction in the environmental reservoir at treatment sites resulted in lower fungal loads on bats compared to untreated control populations. Survival following treatment was also higher in little brown bats (Myotis lucifugus), and trended higher for tricolored bats (Perimyotis subflavus).

Synthesis and applications. Our results highlight that targeted management of sources for environmental transmission can be an effective control strategy for wildlife disease. We found that successfully reducing pathogen in the environment decreased disease severity and increased survival, but required higher treatment exposure than was effective in laboratory experiments, and the effects varied among species. More broadly, our findings have implications for other emerging wildlife diseases with free‐living pathogen stages by highlighting how the degree of environmental contamination can have cascading impacts on hosts, presenting an opportunity for intervention.
Group versus individual occupational therapy for toddlers with autism as a means to improve access to public health‐care services. Randomised controlled pilot study
Authors: Hirschmann Sivan , Magnezi Racheli , Bassan Haim , Tal Orna
Published: February 2023

Introduction

In recent years, the increasing prevalence of autism‐spectrum disorder has resulted in an increased demand for therapies including occupational therapy. In this pilot trial, we aimed to compare the efficacy of group versus individual occupational therapy among toddlers with autism as a means to improve accessibility to care.

Methods

Toddlers (2–4 years) undergoing autism evaluation in our public child developmental centre were recruited and randomised to receive 12 weekly sessions of group or individual occupational therapy based on the same mode of intervention: Developmental, Individual‐Differences and Relationship‐based (DIR). Primary outcomes related to intervention implementation included waiting days, nonattendance, intervention period, number of sessions attended and therapist satisfaction. Secondary outcomes were the Adaptive Behaviour Assessment System questionnaire, the Paediatric Quality of Life Inventory and the Peabody Developmental Motor Scale (PDMS‐2).

Results

Twenty toddlers with autism were included, 10 in each occupational therapy mode of intervention. Children waited fewer days before beginning group occupational therapy compared to individual therapy (52.4 ± 28.1 vs. 108.8 ± 48.0 days p < 0.01). Mean numbers of nonattendance was similar for both interventions (3.2 ± 2.82 vs. 2 ± 1.76, p > 0.05). Worker satisfaction scores were similar at the beginning and end of the study (6.1 ± 0.4 vs. 6.07 ± 0.49, p > 0.05). There were no significant differences between the percentage changes in individual and group therapy outcomes for adaptive score (6.0 ± 16.0 vs. 4.5 ± 17.9, p > 0.05), quality of life (1.3 ± 20.9 vs. 18.8 ± 24.5, p > 0.05) and fine motor skills (13.7 ± 36.1 vs. 15.1 ± 41.5, p > 0.05).

Conclusions

In this pilot study, the group DIR‐based occupational therapy for toddlers with autism improved access to services and allowed earlier interventions, with no clinical inferiority to individual therapy. Further research is required to examine group clinical therapy benefit.
Hsa_circ_0000591 drives osteosarcoma glycolysis and progression by sequestering miR‐194‐5p and elevating HK2 expression
Authors: Wang Dawei , Wang Yang , Wang Huadong , Yang Yafeng , Li Li , Liu Yihao , Yin Xin
Published: February 2023

Osteosarcoma (OS) is the most common bone tumour with a high risk of metastatic progression and recurrence after treatment. Circular RNA hsa_circ_0000591 (circ_0000591) plays a compelling role in OS aggressiveness. However, the function and regulatory mechanism of circ_0000591 need to be further elucidated. As a subject of this study, a differential circRNA circ_0000591 was screened by circRNA microarray expression profiling (GSE96964). Expression changes of circ_0000591 were detected using real‐time quantitative polymerase chain reaction (RT‐qPCR). Effects of circ_0000591 silencing on OS cell viability, proliferation, colony formation, apoptosis, invasion, and glycolysis were determined via functional experiments. The mechanism by which circ_0000591 functions as a molecular sponge for miRNAs was predicted using bioinformatics analysis and validated using dual‐luciferase reporter and RNA pull‐down assays. Xenograft assay was done to validate the function of circ_0000591. Circ_0000591 was strongly expressed in OS samples and cells. Silencing of circ_0000591 lessened cell viability, repressed cell proliferation, invasion, glycolysis, and promoted cell apoptosis. Importantly, circ_0000591 regulated HK2 expression by serving as a miR‐194‐5p molecular sponge. MiR‐194‐5p silencing impaired circ_0000591 downregulation‐mediated suppression of OS cell malignancy and glycolysis. HK2 overexpression weakened the inhibiting impacts of miR‐194‐5p on OS cell malignancy and glycolysis. Also, circ_0000591 silencing decreased xenograft tumour growth in vivo. Circ_0000591 drove OS glycolysis and growth by upregulating HK2 by sequestering miR‐194‐5p. The study highlighted the tumour‐promoting function of circ_0000591 in OS.
Diversity, evolution and life strategies of CbK‐like phages
Authors: Ma Ruijie , Chen Xiaowei , Li Yingying , Jiao Nianzhi , Zhang Rui
Published: February 2023

Caulobacter phage CbK has been extensively studied as a model system in virology and bacteriology. Lysogeny‐related genes have been found in each CbK‐like isolate, suggesting a life strategy of both lytic and lysogenic cycles. However, whether CbK‐related phages can enter lysogeny is still undetermined. This study identified new CbK‐like sequences and expanded the collection of CbK‐related phages. A common ancestry with a temperate lifestyle was predicted for the group, however, which subsequently evolved into two clades of different genome sizes and host associations. Through the examination of phage recombinase genes, alignment of attachment sites on the phage and bacterial genomes (attP–attB pairing), and the experimental validation, different lifestyles were found among the different members. A majority of clade II members retain a lysogenic lifestyle, whereas all clade I members have evolved into an obligate lytic lifestyle via a loss of the gene encoding Cre‐like recombinase and the coupled attP fragment. We postulated that the loss of lysogeny may be a by‐product of the increase in phage genome size, and vice versa. Clade I is likely to overcome the costs through maintaining more auxiliary metabolic genes (AMGs), particularly for those involved in protein metabolism, to strengthen host takeover and further benefit virion production.
Validation of a new method of providing case‐specific time‐of‐death estimates using cadaver temperatures
Authors: Abraham John , Wei Tie , Cheng Lijing
Published: February 2023

The near ubiquitous presence of numerical simulation has made case‐specific calculations of body temperatures following death possible so that accurate calculations of body temperatures can provide valuable information for estimating the time of death and can aid in forensic investigations. Here, a computational approach is described that has been validated against multiple, independent, and experimental investigations. The approach only requires one subjective input parameter (the heat transfer coefficient). A simple algorithm serves as a guidepost to the selection of this parameter. The algorithm incorporates clothing and the space in which the body is housed. Heat transfer coefficients that range from h = 2 W/m2/°C for bodies that are heavily clothed to h = 9 W/m2/°C for bodies that are nude (in air). The method also requires setting of ambient temperature conditions (ambient temperature)—however, that input is often available. The paucity of inputs makes this technique remarkably easy to employ. The new method is also able to calculate cadaver cooling rates for situations where the cadaver is in a timewise or spatially changing thermal environment (diurnal temperature variations, bodies partially submerged in water, changes to weather, insolation, etc.). Results from the present calculations are compared with a large body of measurements from the literature; it was found that the predictions and measurements were in excellent agreement, regardless of the ambient temperature conditions and the nature of the clothing of the body. This new calculation approach can be used with reasonable accuracy for determining cadaver cooling and time since death.
Formation and Evolution of Chromitites in the Hongshishan Complex, Beishan Orogenic Collage, NW China: Constraints from Mineralogical Compositions, Re‐Os Isotopes and Platinum‐Group Element Geochemistry
Authors: WANG Zhaolin , YAN Jiayong , ZHENG Xiaoming , TANG Hejun , YUAN Lulu , DENG Zhen , FANG Tonghui
Published: February 2023

The Hongshishan chromitite deposits are situated to the north of the Beishan orogenic collage, in the southern part of the Central Asian Orogenic Belt. This study describes the mineral chemistry, Re‐Os isotopes and platinum‐group elements geochemistry of the Hongshishan chromitites for the purpose of constraining the origin, evolution and composition of their parental melts. The restricted ranges of Al2O3, Cr2O3 and Cr#‐Mg# variation of chromite‐cores and chromites fall within the field of the mid‐ocean ridge and ophiolitic podiform chromite settings. The (187Os/188Os)i ratios of the chromitites are in the range of 0.12449–0.12745 (average 0.12637) and the γOs are from –1.92 to –0.06 (average –0.83). In the Re‐Os isotope diagrams, all the samples fall in the field of chromitites and show a residual peridotitic trend. The range of Os isotopic compositions and γOs values indicate that they overlap the depleted MORB mantle (DMM) as well as being close to global Os isotopic data and γOs of ophiolite chromitites. The characteristics of the PGE contents can be roughly subdivided into two groups: podiform chromitites and Ural‐Alaskan type complexes. For the ferritchromite cores, the calculated Al2O3 concentrations of the parental melt are higher (average 16.65 wt%) in high‐Cr than high‐Al chromitite (average 16.17 wt%) and for the chromite, the calculated Al2O3 concentrations are even higher (average 16.48 wt%) in the high‐Cr than the high‐Al examples (average 15.38 wt%). In the (TiO2)melt vs. TiO2 diagrams, most high‐Al melts fall in the MORB, while the high‐Cr melts fall in the ARC field. The calculated FeO/MgO ratios for the parental melt show the closest resemblance to a MORB magma composition. The inferred parental melt composition for studied chromitites falls in the field of mid‐ocean ridge basalt (MORB) magmas and far away from boninite. The calculated degrees of partial melting producing the chromitites are 16%–22% (average 19%), which is around the range of those of the MORB magmas. The chromitites are suggested to have been formed in a MORB setting. The chromites and ferritchromite cores are mostly scattered along the MORB and SSZ harzburgite–dunite fields. Ferritchromite rims and ferritchromites with high YFes formed as a result of alteration during serpentinization. .
Ross procedure after prosthetic valve thrombosis in a patient with antiphospholipid syndrome and recurrent bleeding
Authors: Mirzai Saeid , Badwan Osamah Z. , Sankar Parvathy R. , Karmali Rehan , Almaaitah Saja , Gomes Marcelo P. , Miyasaka Rhonda , Quatromoni Neha , Tong Michael Zhen‐Yu , Wassif Heba
Published: February 2023

The Ross procedure allows replacement of a diseased aortic valve with pulmonary root autograft, possibly avoiding the highly thrombotic mechanical valves and immunologic deterioration of tissue valves in antiphospholipid syndrome (APS). Here, we present the use of the Ross procedure in a 42‐year‐old woman with mild intellectual disability, APS, and a complex anticoagulation history after she presented with thrombosis of her mechanical On‐X aortic valve previously implanted for non‐bacterial thrombotic endocarditis.
Debunking the myth of the “robust control regime”: UK arms export controls during war and armed conflict
Authors: Stavrianakis Anna
Published: February 2023

The UK's commitments to conflict prevention and the protection of human rights and international humanitarian law in its arms export controls are now over 20 years old. However, the outbreak of war or conflict has had little or no restraining effect on UK arms exports. This article explores the function of the UK's arms export control regime given that its primary effect is not to restrict arms transfers. I argue that the mantra that the UK has one of the most robust control regimes in the world is not a plausible description of the realities of UK export policy – rather, it is a myth that needs to be debunked. Export controls are primarily mobilised by the state to manage controversy once criticism emerges from civil society and Parliament and thus primarily serve a legitimating function. I illustrate this argument with examples of arms exports in relation to the conflicts in Kashmir, Sri Lanka, the Occupied Palestinian Territory and Yemen, demonstrating three ways in which UK export controls are missing in action: the routine misuse of UK‐supplied weapons; the narrow interpretation of risk in licensing policy; and self‐serving reviews to manage reputation once controversy breaks out.
Unpacking the storytelling around French arms sales: Demystifying the “strategic autonomy” argument
Authors: Soubrier Emma
Published: February 2023

This article looks at the way France's arms exports have historically been framed as an inherent part of the country's core policies to achieve “strategic autonomy” at the domestic and international levels. It posits that taking this argument for granted without subjecting it to critical scrutiny is hazardous because it enables the continued unquestioned support for French arms sales and hampers the development of more stringent export control processes. Today, the need to look beyond this blanket storytelling is heightened in a context where unchecked exports relying on outdated views of global dynamics have precisely started to undermine France's strategic autonomy and interests. Not only does the country's growing dependence on exports create an antinomy of arms sales as a means of strategic independence, but the phenomenon of clients' reverse influence onto suppliers amidst a consolidated buyer's market also calls into question the autonomy of France's foreign policy.
Managers' private communications with analysts: The effect of SEC v. Siebel Systems, Inc.
Authors: Ali Ashiq , Durney Michael T. , Fisch Jill , Kyung Hoyoun
Published: February 2023

In 2005, the SEC suffered a high‐profile loss in its first court case, SEC v. Siebel Systems, Inc., in an effort to enforce Regulation Fair Disclosure (Reg FD). We examine the impact of this loss on managers' selective disclosure to sell‐side analysts. We provide evidence that the informativeness of analyst reports increased after the Siebel decision, especially for observable instances of private meetings. This finding suggests that such selective disclosure increased significantly after the court's decision. Our results also suggest that the increased selective disclosure faded as the SEC resumed enforcement actions related to Reg FD in 2009. In exploratory analyses, we survey and interview law firm partners to investigate possible mechanisms for our results; their responses suggest that the Siebel outcome reduced manager concern about liability from selective disclosure. Collectively, our results highlight how the anticipated costs of regulatory enforcement affect private information flow from managers to analysts in particular.