bluuebunny/crossref_metadata_2025 huggingface dataset:
The Increased Tibiofemoral Rotation: A Potential Contributing Factor for Patellar Maltracking in Patients with Recurrent Patellar Dislocation
Authors: Wu Guan , Cao YanWei , Song GuanYang , Li Yue , Zheng Tong , Zhang Hui , Zhang ZhiJun
Published: June 2022

Objective

The purpose of this study was to analyze the relationship between tibiofemoral rotation and patellar maltracking in patients with recurrent patellar dislocation.

Methods

A total of 143 consecutive knees (118 patients) with clinically diagnosed recurrent patellar dislocation from January 2018 to December 2019 were retrospectively analyzed. Patellar tilt angle and bisect offset index were recorded on axial CT to assesses the severity of patellar maltracking. Tibiofemoral rotation angle is measured by comparing the angle between the posterior femoral and tibial condylar lines on three‐dimensional CT. The Pearson correlation was calculated to investigate the association between tibiofemoral rotation angle and patellar maltracking. Patients were divided into the rotation group (≥15°) and control group (<15°) based on the value of tibiofemoral rotation and a further comparison was performed. To further clarify the complicated relationship among tibial tubercle‐trochlear groove (TT‐TG), tibial tubercle‐posterior cruciate ligament distance (TT‐PCL), tibiofemoral rotation, and patellar maltracking, patients were divided into four subgroups according to the value of TT‐TG and TT‐PCL.

Results

The mean preoperative tibiofemoral rotation angle was 12° ± 6° (range, 0°–31°). Pearson correlation between patellar maltracking parameters (bisect offset index, patellar tilt angle) and various bony deformities found that the tibiofemoral rotation angle was moderately correlated with bisect offset index (r = 0.451, p < 0.001) and patellar tilt angle (r = 0.462, p < 0.001). Further results demonstrated that bisect offset index (152.1 vs 121.2, p < 0.001) and patellar tilt angle (41.2° vs 33.5°, p < 0.001) were significantly higher in the rotation group than that in control group. For patients with a TT‐TG distance of >20 mm, the increased TT‐TG distance was mainly caused by tibiofemoral rotation angle in group C (TT‐TG > 20 mm, TT‐PCL < 24 mm) and predominantly induced by tibial tubercle lateralization in group D (TT‐TG > 20 mm, TT‐PCL > 24 mm). Bisect offset index and patellar tilt angle were significantly higher in the group C than group D.

Conclusion

The increased tibiofemoral rotation angle is associated with patellar maltracking in patients with recurrent patellar dislocation. Patients with increased tibiofemoral rotation angle usually have more severe patellar maltracking.
Understanding immunological origins of atopic dermatitis through multi‐omic analysis
Authors: Beheshti Ramin , Halstead Scott , McKeone Daniel , Hicks Steven D.
Published: June 2022

Background

The pathophysiology of atopic dermatitis (AD) is multifactorial, impacted by individual medical, demographic, environmental, and immunologic factors. This study used multi‐omic analyses to assess how host and microbial factors could contribute to infant AD development.

Methods

This longitudinal cohort study included 129 term infants, identified as AD (n = 37) or non‐AD (n = 92) using the Infant Feeding Practices‐II survey and review of medical records. Standardized surveys were used to assess medical and demographic traits (gestational age, sex, race, maternal AD, and atopy family history), and environmental exposures (delivery method, maternal tobacco use, pets, breastfeeding duration, and timing of solid food introduction). Saliva was collected at 6 months for multi‐omic assessment of cytokines, microRNAs, mRNAs, and the microbiome. The contribution of each factor to AD status was assessed with logistic regression.

Results

Medical, demographic, and environmental factors did not differ between AD and non‐AD infants. Five “omic” factors (IL‐8/IL‐6, miR‐375‐3p, miR‐21‐5p, bacterial diversity, and Proteobacteria) differed between groups (p < .05). The severity of AD was positively associated with levels of miR‐375‐3p (R = .17, p = .049) and Proteobacteria (R = .22, p = .011), and negatively associated with levels of miR‐21‐5p (R = .20, p = .022). Multi‐omic features accounted for 17% of variance between groups, significantly improving an AD risk model employing medical, demographic, and environmental factors (X2 = 32.47, p = .006).

Conclusion

Interactions between the microbiome and host signaling may predispose certain infants to AD by promoting a pro‐inflammatory environment.
How Do Public Managers Learn from Performance Information? Experimental Evidence on Problem Focus, Innovative Search, and Change
Authors: Hansen Jesper Asring , Nielsen Poul Aaes
Published: June 2022

Management decisions are considered important for the performance of public organizations, but how does information about performance influence management decision‐making? Developed from Simon's notion of bounded rationality, the behavioral model of performance‐based learning suggests that managers adjust their understanding of organizational problems, search for information, and consider initiating change when their organization performs below aspirations. In this paper, we offer experimental evidence of how performance information affects the attitudes and decision‐making of public managers. We leverage two experiments conducted among managers in public education. Study 1 uses a question‐order experiment to prime only treated respondents to consider performance, whereas study 2 uses treatments with high‐ and low‐performance signals. We find that low performance affects problem focus but not managers' intention to conduct innovative search. We also find that low‐performance signals increase preferences for immediate performance‐oriented changes but not for other types of changes. We discuss the implications for management decision‐making.

Evidence for Practice

Performance information holds the potential to generate organizational learning and inform public managers' decisions about important problems, priorities, and organizational change.

Public managers become more focused on direct performance‐oriented changes when performance is low, whereas high performance lets them engage in other types of changes.

Performance information alone does not ensure that public managers are focused on generating innovative solutions to performance problems.
Effect of agglomeration on firms’ research and development investment: a U‐shaped relationship
Authors: Li Yuhua , Jian Ze
Published: June 2022

Extant research on how agglomeration affects firms’ R&D investment reveals conflicting views. Some studies suggest that, owing to free riding arising from knowledge spillovers, agglomeration reduces firms’ R&D investment, whereas others find that it creates additional incentives for innovation through intensifying local competition, thereby increasing firms’ R&D investment. Thus, this study attempts to reconcile these two conflicting views. We propose a U‐shaped relationship between agglomeration and firms’ R&D investment; that is, when the extent of agglomeration is low, knowledge spillover effects are important, while local competition is negligible. The free riding effects dominate local competition effects. Therefore, firms’ R&D investment decreases with the extent of agglomeration at a decreasing rate. By contrast, when the extent of agglomeration is high, local competition becomes the dominant force. Consequently, firms’ R&D investment increases with the extent of agglomeration at an increasing rate. Using data from 299,256 manufacturing firms in China, we find that firms’ R&D investment first decreases with the extent of agglomeration to reach a minimum, then increases as the extent of agglomeration continues to rise. These results indicate that there is a robust U‐shaped relationship between agglomeration and firms’ R&D investment.
Effect of addition of ascorbate, dithiothreitol or a caspase‐3 inhibitor to cryopreservation medium on post‐thaw survival of bovine embryos produced in vitro
Authors: Carrascal‐Triana Erly Luisana , Zolini Adriana Moreira , de King Antonio Ruiz , Penitente‐Filho Jurandy Mauro , Hansen Peter J. , Torres Ciro Alexandre Alves , Block Jeremy
Published: June 2022

Experiments were conducted to investigate whether supplementation of cryopreservation medium with ascorbate, dithiothreitol (DTT) or an inhibitor of caspase‐3 (z‐DEVD‐fmk) could improve post‐thaw survival of bovine embryos produced in vitro (IVP). For all experiments, embryos were harvested on day 7 after insemination and subjected to controlled‐rate freezing in medium containing 1.5 M ethylene glycol and treatments as described below. In experiments 1–3, embryos were cryopreserved in freezing medium with ascorbate (0, 0.1, 0.3 or 0.5 mM), DTT (0, 50, 100 or 200 μM) and z‐DEVD‐fmk (0, 50, 100 or 200 μM), respectively. Post‐thaw survival was assessed at 24, 48 and 72 h. For experiments 4–5, embryos were cryopreserved in freezing medium with or without 0.1 mM ascorbate. At 24 h post‐thaw, embryo total cell number, DNA fragmentation and levels of reactive oxygen species (ROS) were evaluated. Embryos subjected to freezing and thawing in medium supplemented with 0.1 mM ascorbate had greater (p < .05) re‐expansion rates at 24, 48 and 72 h and hatching rate at 72 h as compared to embryos not treated with ascorbate. Post‐thaw cryosurvival was not affected by the addition of either DTT or z‐DEVD‐fmk to medium used for cryopreservation. Embryos cryopreserved in medium supplemented with 0.1 mM ascorbate had reduced (p < .001) levels of intracellular ROS and fewer (p < .001) cells with DNA fragmentation. In conclusion, post‐thaw survival of bovine IVP embryos is enhanced by supplementation of freezing medium with ascorbate.
Comparing recalled versus experienced symptoms of breathlessness ratings: An ecological assessment study using mobile phone technology
Authors: Sandberg Jacob , Sundh Josefin , Anderberg Peter , Currow David C. , Johnson Miriam , Lansing Robert , Ekström Magnus
Published: June 2022

Background and objective

Recall of breathlessness is important for clinical care but might differ from the experienced (momentary) symptoms. This study aimed to characterize the relationship between momentary breathlessness ratings and the recall of the experience. It is hypothesized that recall is influenced by the peak (worst) and end (most recent) ratings of momentary breathlessness (peak‐end rule).

Methods

This study used mobile ecological momentary assessment (mEMA) for assessing breathlessness in daily life through an application installed on participants' mobile phones. Breathlessness ratings (0–10 numerical rating scale) were recorded throughout the day and recalled each night and at the end of the week. Analyses were performed using regular and mixed linear regression.

Results

Eighty‐four people participated. Their mean age was 64.4 years, 60% were female and 98% had modified Medical Research Council (mMRC) ≥ 1. The mean number of momentary ratings of breathlessness provided was 7.7 ratings/participant/day. Recalled breathlessness was associated with the mean, peak and end values of the day. The mean was most closely associated with the daily recall. Associations were strong for weekly values: peak breathlessness (beta = 0.95, r2 = 0.57); mean (beta = 0.91, r2 = 0.53); and end (beta = 0.67, r2 = 0.48); p < 0.001 for all. Multivariate analysis showed that peak breathlessness had the strongest influence on the breathlessness recalled at the end of the week.

Conclusion

Over 1 week, recalled breathlessness is most strongly influenced by the peak breathlessness; over 1 day, it is mean breathlessness that participants most readily recalled.
On the Cross-Validation Bias due to Unsupervised Preprocessing
Authors: Moscovich Amit , Rosset Saharon
Published: June 2022

Cross-validation is the de facto standard for predictive model evaluation and selection. In proper use, it provides an unbiased estimate of a model's predictive performance. However, data sets often undergo various forms of data-dependent preprocessing, such as mean-centring, rescaling, dimensionality reduction and outlier removal. It is often believed that such preprocessing stages, if done in an unsupervised manner (that does not incorporate the class labels or response values) are generally safe to do prior to cross-validation. In this paper, we study three commonly practised preprocessing procedures prior to a regression analysis: (i) variance-based feature selection; (ii) grouping of rare categorical features; and (iii) feature rescaling. We demonstrate that unsupervised preprocessing can, in fact, introduce a substantial bias into cross-validation estimates and potentially hurt model selection. This bias may be either positive or negative and its exact magnitude depends on all the parameters of the problem in an intricate manner. Further research is needed to understand the real-world impact of this bias across different application domains, particularly when dealing with small sample sizes and high-dimensional data.
Dentophobia and dental treatment: An umbrella review of the published literature
Authors: Aburas Sarmad , Pfaffeneder‐Mantai Florian , Hofmann Alina , Meller Oliver , Schneider Benedikt , Turhani Dritan
Published: June 2022

Aims

Dentophobia is a well‐know kind of phobia and psychological problem in dentistry. Although patients might suffer from severe oral pain and have serious health complications, dentophobia is still posing a threat to oral healthcare and remains an unresolved worldwide phenomenon. According to estimates, up to 80% of the general population are affected by this condition. Dentophobia is an unpleasant problem with serious consequences not only for patients but also for dentists and the public health system in general. This umbrella review provides a comprehensive overview of the various aspects of dentophoia as addressed in the published literature, and the current level of knowledge concerning their treatment.

Methods and results

Based on 35 reviews of the published literature, addressing various aspects of dentophobia and published between 2008 and 2021, this umbrella review was written. The search was based on the PubMed and PsycINFO databases. The extraction was structured by open coding and each aspect of the subject analyzed according to Ritchie and Lewis.

Conclusion

We conclude that the evidence concerning the efficacy of the various interventions is still rather weak and there is an obvious need for further research, because of the yet and unresolved challenges and the lack of standardised guidelines to deal with patients with dentophobia.
Cyberbullying and empathy among elementary school students: Do special educational needs make a difference?
Authors: Touloupis Thanos , Athanasiades Christina
Published: June 2022

The present study investigates involvement in cyberbullying and empathy skills, as well as the relationship between the two among general education sixth grade elementary school students with and without special educational needs (SEN). Specifically, 120 students with SEN (Autistic Spectrum Disorder‐ASD, Attention Deficit Hyperactivity Disorder‐ADHD, learning disabilities) and 120 students without SEN from 29 randomly selected schools of the second biggest city in Greece completed a self‐report questionnaire, which included a short version of the “Cyberbullying Questionnaire” (Smith et al., An investigation into cyber bullying, its forms, awareness and impact, and the relationship between age and gender in cyber bullying. A report to the Anti‐Bullying Alliance. Unit for School and Family Studies, 2006) and the “Basic Empathy Scale”—BES (Jolliffe & Farrington, 2006, J Adolesc, 29:589, 2006). The results showed that, regardless of gender, involvement in cyberbullying (as victims/bullies) concerned primarily students with SEN, mainly those with ASD and ADHD. Accordingly, students with SEN and mostly those with ASD expressed lower affective and cognitive empathy compared to the rest of the students. Finally, for all the participating students both affective and cognitive empathy negatively predicted engagement in cyberbullying (as victims/bullies). Implications for preventive actions in elementary education, and especially for children with SEN, are discussed in detail.
The link between cognitive and affective empathy and interpersonal emotion regulation direction and strategies
Authors: Chavira Trujillo Gabriel , Gallego Tomás María , López‐Pérez Belén
Published: June 2022

Interpersonal emotion regulation (ER) refers to the different processes aimed at changing the emotional states of others. Some authors have speculated about the pivotal role of empathy for interpersonal ER to happen. However, the very limited empirical evidence suggests that only cognitive empathy as opposed to affective empathy may be a necessary antecedent. As previous research only considered interpersonal affect improvement and showed mixed evidence for the regulation strategies, we aimed to address this gap in the current research. To that aim, 374 adults (M = 30.3 years, 249 female) reported their tendency to engage in cognitive (perspective‐taking) and affective empathy (empathic concern and personal distress) as well as their tendency to improve and worsen others' mood, and to use different regulation strategies (situation modification, attention deployment, cognitive change, and modulation of the emotional response) to change others' feelings. Results of the regression analyses showed that while affect improvement was not significantly predicted by any of the empathy variables, affect worsening was positively predicted by personal distress. Concerning the regulation strategies, while cognitive change and situation modification were positively predicted by personal distress, attention deployment was positively predicted by perspective‐taking. Overall, the obtained results highlight the need to further investigate the link between empathy and ER and to carefully consider the methods selected for that purpose.
Are attitudes in employees of public employment service in line with the principles of individual placement and support? A questionnaire‐based survey
Authors: Brinchmann Beate , Rinaldi Miles , Sandtorv Elisabeth , Moe Cathrine Fredriksen , McDaid David , Killackey Eóin , Mykletun Arnstein
Published: June 2022

A high proportion of people with severe mental illness (SMI) want to work, consider it essential for recovery, yet employment rates are low. Many employees in public employment services (PES) work according to traditional attitudes that people with SMI are unable to work and if they do, risk harm from work‐related stress. These attitudes conflict with principles in evidence based vocational models like individual placement and support (IPS) and probably contributes to the low‐employment rate. The aim of this study was to investigate attitudes towards the evidence‐based principles of IPS among PES employees with and without exposure to IPS. A case vignette describing a person with SMI and statements referring to this vignette was developed and administered to PES employees at two timepoints, 4 years apart. Respondents indicated their attitudes on a six‐point Likert scale to statements in accordance to the principles of IPS. Independent two‐tailed sample t‐tests were used to analyse differences between respondents in municipalities with IPS exposure, compared to municipalities without. Multiple linear regressions with attitudes as a dependent variable was used to test whether attitudes changed over time dependent on exposure to IPS. Attitudes were generally aligned with IPS principles compared to current PES practice. The municipality with IPS exposure had more favourable attitudes (p < 0.01). Changes in attitudes were minimal over time and did not differ between regions (p < 0.287). Attitudes of employees in PES are aligned with the principles of IPS and to a greater extent if exposed to IPS.
Stabilized Explicit Integrators for Local Parametrization in Multi-Rigid-Body System Dynamics
Authors: Zhou Ping , Ren Hui
Published: June 2022

In this work, stabilized explicit integrators for local parametrization are introduced to calculate the dynamics of constrained multi-rigid-body systems, including those based on the orthogonal Runge–Kutta–Chebyshev (RKC) method and the extrapolated stabilized explicit Runge–Kutta (ESERK) method. Both of these methods have large stability regions at the negative real axis, and this property makes them suitable to settle the introduction of the stabilization parameter for a constraint equation. The local vectorial rotation parameters are adopted to describe rotations in each rigid body, and a stabilization technique is developed to transform the differential-algebraic equations (DAE) into a set of first-order ordinary differential equations (ODEs) that can be computed efficiently. Several benchmarks are calculated and the results are compared to those by the generalized-α integrator and ADAMS models, verifying their effectiveness in nonstiff problems.
A Phase Diagram-Based Stability Design Method for a Symmetrical Origami Waterbomb Base
Authors: Zhang Hongchuan , Zhu Benliang , Chen Bicheng , Cui Chaoyu , Li Hai , Zhang Xianmin
Published: June 2022

The symmetrical origami waterbomb (WB) base shows promising applications in engineering due to its considerable mechanical behaviors. As a common phenomenon in actual origami, the stability performance of the WB base has attracted increasing attention. However, there are few studies on graphical design for the stability of WB bases. Based on the phase diagram of the intrinsic parameters, this paper proposes an intuitive and synthesized stability design method for the WB base. First, the basic principles are demonstrated using the Euler–Lagrange functional equation. In addition, the details of the method are illustrated by two typical WB bases with a given stiffness ratio. Second, according to the proposed design method, case studies are presented, and the stability behaviors are evaluated by the analytical method and finite element analysis (FEA) simulation. Finally, the prototypes of the case study are designed, and a measurement experiment of the stable states is carried out. Both FEA simulation and the experimental result demonstrate the effectiveness of the proposed design method.
Estimation of Small Failure Probability Based on Adaptive Subset Simulation and Deep Neural Network
Authors: Peng Xiang , Shao Yujie , Hu Weifei , Li Jiquan , Liu Zhenyu , Jiang Shaofei
Published: June 2022

The critical problem of reliability design is how to obtain a more accurate failure probability with a smaller number of evaluations of actual complex and nonlinear performance function. To achieve this objective, an adaptive subset simulation method with a deep neural network (DNN) is proposed for accurate estimation of small failure probability. A determinate criterion for threshold values is developed, and the subset number is adaptively quantified according to the initial estimated value of small failure probability. Therefore, the estimation of small failure probability is converted to estimation problem of multiple large conditional probabilities. An adaptive deep neural network model is constructed in every subset to predict the conditional probability with a smaller number of evaluations of the actual performance function. Furthermore, the sampling points for the next subset can be adaptively selected according to the constructed DNN model, which can decrease the number of invalid sampling points and evaluations of actual performance function, then the computational efficiency for estimating the conditional probability in every subset is increased. The sampling points with high probability density functions are recalculated with actual performance function values to replace the predicted values of the DNN model, which can verify the accuracy of DNN model and increase the estimation accuracy of small failure probability. By analyzing a nonlinear problem, a multiple failure domain problem and two engineering examples, the effectiveness and accuracy of the proposed methodology for estimating small failure probability are verified.
Applying Infrared Thermography as a Method for Online Monitoring of Turbine Blade Coolant Flow
Authors: DeShong Eric , Peters Benjamin , Paynabar Kamran , Gebraeel Nagi , Thole Karen A. , Berdanier Reid A.
Published: June 2022

As gas turbine engine manufacturers strive to implement condition-based operation and maintenance, there is a need for blade monitoring strategies capable of early fault detection and root-cause determination. Given the importance of blade cooling flows to turbine blade health and longevity, there is a distinct lack of methodologies for coolant flowrate monitoring. The present study addresses this identified opportunity by applying an infrared thermography system on an engine-representative research turbine to generate data-driven models for prediction of blade coolant flowrate. Thermal images were used as inputs to a linear regression and regularization algorithm to relate blade surface temperature distribution with blade coolant flowrate. Additionally, this study investigates how coolant flowrate prediction accuracy is influenced by the number and breadth of diagnostic measurements. The results of this study indicate that a source of high-fidelity training data can be used to predict blade coolant flowrate within about six percent error. Furthermore, identification of prioritized sensor placement supports application of this technique across multiple sensor technologies capable of measuring blade surface temperature in operating gas turbine engines, including spatially resolved and point-based measurement techniques.
Uppsala and Berkeley: Two essential laboratories in the development of modern photoelectron spectroscopy
Authors: Martensson Nils , Föhlisch Alexander , Svensson Svante
Published: June 2022

The development of modern photoelectron spectroscopy is reviewed with a special focus on the importance of research at Uppsala University and at Berkeley. The influence of two pioneers, Kai Siegbahn and Dave Shirley, is underlined. Early interaction between the two centers helped to kick-start the field. Both laboratories have continued to play an important role in the field, both in terms of creating new experimental capabilities and developing the theoretical understanding of the spectroscopic processes.
Adapting an Evidence-Based Exercise and Education Program for Older Breast Cancer Survivors for the REJOIN Trial
Authors: Bluethmann Shirley M. , Flores Eileen , Grotte Meghan , Heitzenrater Jared , Truica Cristina I. , Olsen Nancy J. , Sciamanna Christopher , Schmitz Kathryn H.
Published: June 2022

Physical activity (PA) promotes survival and mitigates symptoms in older breast cancer survivors (BCS), especially to reduce joint pain associated with adjuvant hormonal treatment. The purpose is to describe the adaptation process for an evidence-based exercise and education curriculum (i.e., Fit & Strong!) to support older BCS participating in the Using Exercise to Relieve Joint Pain and Improve Aromatase Inhibitor Adherence in Older Breast Cancer Survivors trial. We reviewed all educational materials with scientific/clinical experts to identify necessary content changes. Next, we conducted semistructured phone interviews with BCS to review all educational materials and conducted a real-time pretest for the trial. Overall, BCS found the adapted materials and experience acceptable (mean score of 9.2/10 for satisfaction). Content changes included simplifying exercise instructions, prioritizing content related to the trial goals, and updating photographs. Because of COVID, the pretest was conducted via Zoom. Our multistep adaptation process provided an acceptable intervention to meet the needs of older BCS. Lessons learned will be applied to the forthcoming pilot trial.
Destabilization of deep oxidized mantle drove the Great Oxidation Event
Authors: O’Neill Craig , Aulbach Sonja
Published: June 2022

The rise of Earth’s atmospheric O
2
levels at ~2.4 Ga was driven by a shift between increasing sources and declining sinks of oxygen. Here, we compile recent evidence that the mantle shows a significant increase in oxidation state leading to the Great Oxidation Event (GOE), linked to sluggish upward mixing of a deep primordial oxidized layer. We simulate this scenario by implementing a new rheological model for this oxidized, bridgmanite-enriched viscous material and demonstrate slow mantle mixing in simulations of early Earth’s mantle. The eventual homogenization of this layer may take ~2 Ga, in line with the timing of the observed mantle redox shift, and would result in the increase in upper mantle oxidation of >1 log(
f
O
2
) unit. Such a shift would alter the redox state of volcanic degassing products to more oxidized species, removing a major sink of atmospheric O
2
and allowing oxygen levels to rise at ~2.4 Ga.
Exosome-mediated genetic reprogramming of tumor-associated macrophages by exoASO-STAT6 leads to potent monotherapy antitumor activity
Authors: Kamerkar Sushrut , Leng Charan , Burenkova Olga , Jang Su Chul , McCoy Christine , Zhang Kelvin , Dooley Kevin , Kasera Samuel , Zi Tong , Sisó Sílvia , Dahlberg William , Sia Chang Ling , Patel Shil , Schmidt Karl , Economides Kyriakos , Soos Timothy , Burzyn Dalia , Sathyanarayanan Sriram
Published: June 2022

Effectiveness of checkpoint immunotherapy in cancer can be undermined by immunosuppressive tumor-associated macrophages (TAMs) with an M2 phenotype. Reprogramming TAMs toward a proinflammatory M1 phenotype is a novel approach to induce antitumor immunity. The M2 phenotype is controlled by key transcription factors such as signal transducer and activator of transcription 6 (STAT6), which have been “undruggable” selectively in TAMs. We describe an engineered exosome therapeutic candidate delivering an antisense oligonucleotide (ASO) targeting STAT6 (exoASO-STAT6), which selectively silences STAT6 expression in TAMs. In syngeneic models of colorectal cancer and hepatocellular carcinoma, exoASO-STAT6 monotherapy results in >90% tumor growth inhibition and 50 to 80% complete remissions. Administration of exoASO-STAT6 leads to induction of nitric oxide synthase 2 (
NOS2
), an M1 macrophage marker, resulting in remodeling of the tumor microenvironment and generation of a CD8 T cell–mediated adaptive immune response. Collectively, exoASO-STAT6 represents the first platform targeting transcription factors in TAMs in a highly selective manner.
Muscle mitochondrial remodeling by intermittent glucocorticoid drugs requires an intact circadian clock and muscle PGC1α
Authors: Quattrocelli Mattia , Wintzinger Michelle , Miz Karen , Levine Daniel C. , Peek Clara Bien , Bass Joseph , McNally Elizabeth M.
Published: June 2022

Exogenous glucocorticoids interact with the circadian clock, but little attention is paid to the timing of intake. We recently found that intermittent once-weekly prednisone improved nutrient oxidation in dystrophic muscle. Here, we investigated whether dosage time affected prednisone effects on muscle bioenergetics. In mice treated with once-weekly prednisone, drug dosing in the light-phase promoted nicotinamide adenine dinucleotide (NAD+) levels and mitochondrial function in wild-type muscle, while this response was lost with dark-phase dosing. These effects depended on a normal circadian clock since they were disrupted in muscle from [Brain and muscle Arnt-likeprotein-1(Bmal1)]–knockout mice. The light-phase prednisone pulse promoted BMAL1-dependent glucocorticoid receptor recruitment on noncanonical targets, includingNamptandPpargc1a[peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α)]. In mice with muscle-restricted inducible PGC1α ablation, bioenergetic stimulation by light-phase prednisone required PGC1α. These results demonstrate that glucocorticoid “chronopharmacology” for muscle bioenergetics requires an intact clock and muscle PGC1α activity.
Voltage-gated Ca
2+
channel proteins do not function as ion channels in T cells
Authors: Cahalan Michael D.
Published: June 2022

Calcium (Ca
2+
) signaling has long been known to be crucial for T cell activation. Erdogmus
et al
. tested the function of voltage-gated Ca
2+
channel (CaV) proteins and discovered a nonchannel function mediated by an accessory subunit but found no evidence for CaV channel activity in T cells.
Efficacy of Cochleated Amphotericin B in Mouse and Human Mucocutaneous Candidiasis
Authors: Desai Jigar V. , Urban Amanda , Swaim Doris Z. , Colton Benjamin , Kibathi Lilian W. , Ferrè Elise M. N. , Stratton Pamela , Merideth Melissa A. , Hunsberger Sally , Matkovits Theresa , Mannino Raphael , Holland Steven M. , Tramont Edmund , Lionakis Michail S. , Freeman Alexandra F.
Published: June 2022

Candida albicans
causes debilitating, often azole-resistant, infections in patients with chronic mucocutaneous candidiasis (CMC). Amphotericin B (AMB) resistance is rare, but AMB use is limited by parenteral administration and nephrotoxicity.
Stimulating Effect of
Trichococcus flocculiformis
on a Coculture of
Syntrophomonas wolfei
and
Methanospirillum hungatei
Authors: Doloman Anna , Boeren Sjef , Miller Charles D. , Sousa Diana Z.
Published: June 2022

Results from the present study open doors to fascinating research on complex microbial cultures in anaerobic environments (of biotechnological and ecological relevance). Such studies of defined mixed populations are critical to understanding the highly intertwined natural and engineered microbial systems and to developing more reliable and trustable metabolic models.
Role of
Staphylococcus aureus
Tet38 in Transport of Tetracycline and Its Regulation in a Salt Stress Environment
Authors: Truong-Bolduc Q. C. , Wang Y. , Hooper D. C.
Published: June 2022

This study shows that
S. aureus
Tet38 is a tetracycline efflux pump regulated by KdpD/E regulator. These findings are the first direct demonstration of Tet38-mediated tetracycline efflux, which had previously been inferred from its ability to confer tetracycline resistance.
Bacterial Necromass Is Rapidly Metabolized by Heterotrophic Bacteria and Supports Multiple Trophic Levels of the Groundwater Microbiome
Authors: Geesink Patricia , Taubert Martin , Jehmlich Nico , von Bergen Martin , Küsel Kirsten
Published: June 2022

Subsurface microbiomes provide essential ecosystem services, like the generation of drinking water. These ecosystems are devoid of light-driven primary production, and microbial life is adapted to the resulting oligotrophic conditions.
A Third Way of Energy Conservation in Acetogenic Bacteria
Authors: Kremp Florian , Roth Jennifer , Müller Volker
Published: June 2022

Acetogenic bacteria grow by making acetate from CO
2
and are considered the first life forms on Earth since they couple CO
2
reduction to the conservation of energy. How this is achieved has been an enigma ever since.
Metastable Semimetallic Solid Atomic Phase of Nitrogen
Authors: Grishakov K. S. , Degtyarenko N. N.
Published: June 2022

A new solid atomic phase of nitrogen, which is dynamically stable at pressures above 20 GPa, has been predicted within the density functional theory. This phase has a low symmetry of the crystal lattice $$P\bar {1}$$ and exhibits electronic properties unique for nitrogen crystal structures in the low-pressure region, which are characteristic of semimetals. The structural, energy, mechanical, and electronic properties of this phase are calculated and compared with similar characteristics of the gauche phase of nitrogen.
Chlamydia trachomatisconjunctivitis in the pre-pubertal child
Authors: Moore Rebecca , Mallett Peter , Hull Sarah , Christie Sharon , Simpson Emma , Bowen Jackie , Dinsmore Wallace , McCaughey Conall , Livingstone Alison
Published: June 2022

Much is reported in the literature about the transmission and presentation ofChlamydia trachomatisconjunctival infection in the neonate; however, there is a paucity of information available on infection in the older pre-pubertal child (>3 years of age). We present the case of a 7-year-old girl, referred for assessment at the sexual assault referral centre following the diagnosis of unilateralC. trachomatisconjunctivitis. This child underwent a rigorous multiagency child protection process, with input from medical professionals, social services and the police to investigate the possibility of child sexual abuse (CSA). However, a group consensus was reached that non-sexual close contact transfer ofC. trachomatisfrom the mother was the most likely mode of transmission and cause of infection. We aim to take the reader through the complex path to this conclusion, the approach to sexually transmitted infections and potential CSA and what is currently known about chlamydial conjunctivitis in children beyond the neonatal period.
Intracranial extraosseous dural-based Ewing’s sarcoma with fluid-haematocrit levels: imaging findings of a rare tumour
Authors: Mohakud Sudipta , Rajasimman Aishvarya Shri , Purkait Suvnedu , Naik Suprava
Published: June 2022

Extraosseous dural-based primary Ewing’s sarcoma of the central nervous system is a rare tumour posing a diagnostic challenge. On cross-sectional radiological imaging, the lesion has an extra-axial location with heterogeneous appearance. These lesions are usually multicystic with internal haemorrhage causing fluid-haematocrit levels. It mimics conditions like an aneurysmal bone cyst, microcystic meningioma, telangiectatic osteosarcoma or cystic metastasis. Exclusion of primary Ewing’s sarcoma or malignancy elsewhere in the body is required to rule out a secondary. Surgery along with adjuvant chemotherapy and focal radiotherapy is the preferred mode of treatment. Due to the presence of non-specific small round blue cells on H&E stain, these tumours are also confused with lymphoma, osteosarcoma, rhabdomyosarcoma, Merkel cell carcinoma, ependymoblastoma and neuroendocrine carcinoma. Immunohistochemistry provides a definitive diagnosis. A high degree of suspicion in the preoperative scans is crucial for prognostication and early management of this aggressive tumour leading to improved patient survival.
Effect of eyelid muscle action and rubbing on telemetrically obtained intraocular pressure in patients with glaucoma with an IOP sensor implant
Authors: van den Bosch Jacqueline J O N , Pennisi Vincenzo , Mansouri Kaweh , Weinreb Robert N , Thieme Hagen , Hoffmann Michael B , Choritz Lars
Published: June 2022

Background

Patients with glaucoma on topical glaucoma medication are often affected by dry eye symptoms and thus likely to rub or squeeze their eyelids. Here, we telemetrically measure peak intraocular pressure (IOP) during eyelid manoeuvres and eyelid rubbing.

Methods

Eleven patients with primary open-angle glaucoma (POAG) previously implanted with a telemetric IOP sensor (Eyemate-IO) were instructed to look straight ahead for 1 min as a baseline measurement. Next, 6 repeats of blinking on instruction with 10 s intervals in between were performed. In addition, 5 repeats of eyelid closure (n=9), eyelid squeezing and eyelid rubbing (n=7) were performed with 15 s intervals in between. IOP was recorded via an external antenna placed around the study eye. Average peak IOP increases from baseline were analysed and tested against zero (no change) with one-sample t-tests.

Results

For eyelid rubbing, the average peak ∆ IOP increase (mean±SEM) was 59.1±9.6 mm Hg (p<0.001) from baseline. It was 42.2±5.8 mm Hg (p<0.0001) for eyelid squeezing, 3.8±0.6 mm Hg (n=9, p<0.01) for eyelid closure and 11.6±2.4 mm Hg (p<0.001) for voluntary blinking. No IOP change except for a short irregularity in the ocular pulse was observed during involuntary blinking.

Conclusion

Eyelid manoeuvres in patients with POAG elicited brief increases in IOP that were particularly large with squeezing and rubbing. Further investigation of the potential implications for glaucoma progression is warranted.
Closure of recurrent colovaginal fistulas using AMPLATZER occluder device
Authors: Simmons Joseph , Sherif Ahmed , Mader Jason , Altarawneh Saba , El-Hamdani Mehiar , Frandah Wesam
Published: June 2022

A 79-year-old woman and a 92-year-old woman were referred to the gastroenterology department for management of persistent colovaginal fistula despite surgical and non-surgical management. Both patients had several hospitalisations for recurrent urinary tract infections. After failed surgical management and endoscopy using over-the-scope clipping, both patients underwent endoscopic closure using the Amplatzer cardiac septal occluder device. Both patients underwent successful closure and had no recurrence of symptoms at 6-month follow-up. Although there are several therapies available for persistent colovaginal fistulas, most involve multiple sessions and have high recurrence rate. There have been reports in the literature of cardiac septal occluders being used in the management of upper gastrointestinal tract fistulas, but few cases exist explaining their role in the management of colovaginal fistulas. Our cases demonstrate that cardiac septal occluders may be a viable option for management of fistulas and warrants further studies to reproduce its effectiveness and safety.
Patients’ acceptability and implementation outcomes of a case management approach to encourage participation in colorectal cancer screening for people with schizophrenia: a qualitative secondary analysis of a mixed-method randomised clinical trial
Authors: Yamada Yuto , Fujiwara Masaki , Shimazu Taichi , Etoh Tsuyoshi , Kodama Masafumi , So Ryuhei , Matsushita Takanori , Yoshimura Yusaku , Horii Shigeo , Fujimori Maiko , Takahashi Hirokazu , Nakaya Naoki , Miyaji Tempei , Hinotsu Shiro , Harada Keita , Okada Hiroyuki , Uchitomi Yosuke , Yamada Norihito , Inagaki Masatoshi
Published: June 2022

Objectives

We examined the efficacy of case management (CM) interventions to encourage participation in colorectal cancer screening for patients with schizophrenia. This study aimed to clarify patients’ acceptability of the intervention and the helpful components of the intervention. Simultaneously, the study aimed to determine the acceptability, appropriateness and feasibility of the intervention from the perspective of psychiatric care providers.

Study design and setting

This study was a secondary qualitative analysis of a mixed-method randomised controlled trial that evaluated the efficacy of the CM approach to encourage participation in cancer screening for people with schizophrenia. The intervention comprised education and patient navigation for colorectal cancer screening. Interviews were conducted with patients who received the intervention and staff from two psychiatric hospitals in Japan who delivered the intervention.

Participants

Of the 172 patients with schizophrenia who participated in the trial, 153 were included. In addition, three out of six providers were included.

Data collection and analysis

Using a structured interview, the case manager asked participants about patient acceptability and the helpful components of the intervention. Content analysis was conducted for the responses obtained, and the number of responses was tabulated by two researchers. For the interviews with the providers, opinions obtained from verbatim transcripts were extracted and summarised.

Results

Forty-three of the 56 patients perceived that the intervention was acceptable. For the intervention component, inperson counselling with an explanation of the screening process by psychiatric care providers was most frequently reported by the patients as helpful (48 of the 68 respondents). Psychiatric care providers evaluated the intervention as acceptable, appropriate and easy to understand and administer. However, providing the intervention to all patients simultaneously was considered difficult with the current human resources.

Conclusions

This study showed that the CM intervention was perceived as acceptable by patients and acceptable and appropriate by psychiatric care providers.

Trial registration number

UMIN000036017.
COVID-19 and liver disease
Authors: Dufour Jean-François , Marjot Thomas , Becchetti Chiara , Tilg Herbert
Published: June 2022

Knowledge on SARS-CoV-2 infection and its resultant COVID-19 in liver diseases has rapidly increased during the pandemic. Hereby, we review COVID-19 liver manifestations and pathophysiological aspects related to SARS-CoV-2 infection in patients without liver disease as well as the impact of COVID-19 in patients with chronic liver disease (CLD), particularly cirrhosis and liver transplantation (LT). SARS-CoV-2 infection has been associated with overt proinflammatory cytokine profile, which probably contributes substantially to the observed early and late liver abnormalities. CLD, particularly decompensated cirrhosis, should be regarded as a risk factor for severe COVID-19 and death. LT was impacted during the pandemic, mainly due to concerns regarding donation and infection in recipients. However, LT did not represent a risk factor per se of worse outcome. Even though scarce, data regarding COVID-19 specific therapy in special populations such as LT recipients seem promising. COVID-19 vaccine-induced immunity seems impaired in CLD and LT recipients, advocating for a revised schedule of vaccine administration in this population.
Association between SCN5A R225Q variant and dilated cardiomyopathy: potential role of intracellular pH and WNT/β-catenin pathway
Authors: Hu Jingjing , Yang Kun , Zhao Yongchao , Wei Zilun , Yang Lebing , Gao Rifeng , Wu Yonghui , Xu Lei , Xu Sujuan , Hu Kai , Sun Aijun , Ge Junbo
Published: June 2022

Background

The SCN5A variant is a common cause of familial dilated cardiomyopathy (DCM). We previously reported a SCN5A variant (c.674G>A), located in the high-risk S4 segment of domain I (DI-S4) region in patients with idiopathic DCM and R225Q knockin (p.R225Q) mice carrying the c.674G>A variant exhibited prolonged baseline PR intervals without DCM phenotypes. In this study, we explored the association and mechanism between R225Q variant and DCM phenotype.

Methods

Prevalence of DI-S4 variant was compared between patients with idiopathic DCM and the control participants. R225Q knockin and wild-type (WT) mice were subjected to doxorubicin (DOX), D-galactose (D-gal) or D-gal combined with DOX.

Results

Clinical data suggested that the prevalence of DI-S4 variant was higher in DCM group than in the control group (4/90 (4.4%) vs 3/1339 (0.2%), p<0.001). Cardiomyocytes from R225Q knockin mice treated with D-gal and DOX exhibited more significant hypertrophic phenotype and weaker contraction/dilation function and an increased level of apoptosis as compared with WT mice. Mechanistically, we found that R225Q variant could increase intracellular pH and further induce the activation of the WNT/β-catenin pathway as well as the overexpression of pro-hypertrophic and pro-apoptotic targets. WNT-C59 inhibitor improved cardiac function in the R225Q knockin mice treated with D-gal and DOX.

Conclusion

Our results suggest that R225Q variant is associated with increased susceptibility to DCM. Ageing could enhance this process via activating WNT/β-catenin signaling in response to increased intracellular pH. Antagonising the WNT/β-catenin pathway might be a potential therapeutic strategy for mitigating R225Q variant-related DCM pathogenesis.