bluuebunny/crossref_metadata_2025 huggingface dataset:
Knee acoustic emissions as a noninvasive biomarker of articular health in patients with juvenile idiopathic arthritis: a clinical validation in an extended study population
Authors: Goossens Quentin , Locsin Miguel , Gharehbaghi Sevda , Brito Priya , Moise Emily , Ponder Lori A , Inan Omer T , Prahalad Sampath
Published: June 2023

Background

Joint acoustic emissions from knees have been evaluated as a convenient, non-invasive digital biomarker of inflammatory knee involvement in a small cohort of children with Juvenile Idiopathic Arthritis (JIA). The objective of the present study was to validate this in a larger cohort.

Findings

A total of 116 subjects (86 JIA and 30 healthy controls) participated in this study. Of the 86 subjects with JIA, 43 subjects had active knee involvement at the time of study. Joint acoustic emissions were bilaterally recorded, and corresponding signal features were used to train a machine learning algorithm (XGBoost) to classify JIA and healthy knees. All active JIA knees and 80% of the controls were used as training data set, while the remaining knees were used as testing data set. Leave-one-leg-out cross-validation was used for validation on the training data set. Validation on the training and testing set of the classifier resulted in an accuracy of 81.1% and 87.7% respectively. Sensitivity / specificity for the training and testing validation was 88.6% / 72.3% and 88.1% / 83.3%, respectively. The area under the curve of the receiver operating characteristic curve was 0.81 for the developed classifier. The distributions of the joint scores of the active and inactive knees were significantly different.

Conclusion

Joint acoustic emissions can serve as an inexpensive and easy-to-use digital biomarker to distinguish JIA from healthy controls. Utilizing serial joint acoustic emission recordings can potentially help monitor disease activity in JIA affected joints to enable timely changes in therapy.
Inhibition of the MEK/ERK pathway suppresses immune overactivation and mitigates TDP-43 toxicity in a Drosophila model of ALS
Authors: Yue Wenkai , Deng Xue , Wang Zhao , Jiang Mingsheng , Hu Rirong , Duan Yongjia , Wang Qiangqiang , Cui Jihong , Fang Yanshan
Published: June 2023

TDP-43 is an important DNA/RNA-binding protein that is associated with age-related neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD); however, its pathomechanism is not fully understood. In a transgenic RNAi screen usingDrosophilaas a model, we uncovered that knockdown (KD) ofDsor1(theDrosophilaMAPK kinasedMEK) suppressed TDP-43 toxicity without altering TDP-43 phosphorylation or protein levels. Further investigation revealed that theDsor1downstream generl(dERK) was abnormally upregulated in TDP-43 flies, and neuronal overexpression ofdERKinduced profound upregulation of antimicrobial peptides (AMPs). We also detected a robust immune overactivation in TDP-43 flies, which could be suppressed by downregulation of the MEK/ERK pathway in TDP-43 fly neurons. Furthermore, neuronal KD of abnormally increased AMPs improved the motor function of TDP-43 flies. On the other hand, neuronal KD ofDnr1, a negative regulator of theDrosophilaimmune deficiency (IMD) pathway, activated the innate immunity and boosted AMP expression independent of the regulation by the MEK/ERK pathway, which diminished the mitigating effect of RNAi-dMEKon TDP-43 toxicity. Finally, we showed that an FDA-approved MEK inhibitor trametinib markedly suppressed immune overactivation, alleviated motor deficits and prolonged the lifespan of TDP-43 flies, but did not exhibit a lifespan-extending effect in Alzheimer disease (AD) or spinocerebellar ataxia type 3 (SCA3) fly models. Together, our findings suggest an important role of abnormal elevation of the MEK/ERK signaling and innate immunity in TDP-43 pathogenesis and propose trametinib as a potential therapeutic agent for ALS and other TDP-43-related diseases.
Within- and between-therapist agreement on personalized parameters for robot-assisted gait therapy: the challenge of adjusting robotic assistance
Authors: van Dellen Florian , Aurich-Schuler T. , Labruyère Rob
Published: June 2023

Background

Stationary robotic gait trainers usually allow for adjustment of training parameters, including gait speed, body weight support and robotic assistance, to personalize therapy. Consequently, therapists personalize parameter settings to pursue a relevant therapy goal for each patient. Previous work has shown that the choice of parameters influences the behavior of patients. At the same time, randomized clinical trials usually do not report the applied settings and do not consider them in the interpretation of their results. The choice of adequate parameter settings therefore remains one of the major challenges that therapists face in everyday clinical practice. For therapy to be most effective, personalization should ideally result in repeatable parameter settings for repeatable therapy situations, irrespective of the therapist who adjusts the parameters. This has not yet been investigated. Therefore, the aim of the present study was to investigate the agreement of parameter settings from session to session within a therapist and between two different therapists in children and adolescents undergoing robot-assisted gait training.

Methods and results

Fourteen patients walked in the robotic gait trainer Lokomat on 2 days. Two therapists from a pool of 5 therapists independently personalized gait speed, bodyweight support and robotic assistance for a moderately and a vigorously intensive therapy task. There was a very high agreement within and between therapists for the parameters gait speed and bodyweight support, but a substantially lower agreement for robotic assistance.

Conclusion

These findings imply that therapists perform consistently at setting parameters that have a very clear and visible clinical effect (e.g. walking speed and bodyweight support). However, they have more difficulties with robotic assistance, which has a more ambiguous effect because patients may respond differently to changes. Future work should therefore focus on better understanding patient reactions to changes in robotic assistance and especially on how instructions can be employed to steer these reactions. To improve the agreement, we propose that therapists link their choice of robotic assistance to the individual therapy goals of the patients and closely guide the patients during walking with instructions.
Prevalence and clinicopathological associations of HER2 expression in non-small cell lung cancer: a retrospective study in Jordanian patients
Authors: Abu Al Karsaneh Ola , Al Anber Arwa , ALQudah Mohammad , Al-Mustafa Sahar , AlMa’aitah Hussien , Sughayer Maher
Published: June 2023

Background

Human epidermal growth factor receptor 2 (HER2), a promising therapeutic target, can be mutated, amplified, or overexpressed in different malignancies, including non-small cell lung cancer (NSCLC). Although these alterations showed adverse prognostic effects in many cancers, their clinical significance in NSCLC is controversial. This study primarily assessed the prevalence of HER2 protein expression in NSCLC among Jordanian patients. In addition, the possible association between HER2 protein expression and clinicopathological variables was evaluated.

Methods

A total of 100 surgically resected NSCLC cases treated at King Hussein Cancer Center (KHCC) between 2009 and 2021 were examined for HER2 protein expression using immunohistochemistry (IHC). The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines for breast cancer were applied to interpret the results with a final score ranging from 0 to 3+, considering a score of 3 + as overexpression. Additionally, a separate subset of patients was tested for HER2 gene mutation. Fisher’s exact test was used to assess the association between HER2 scores and the other variables. Kaplan-Meier method was used to calculate survival.

Results

Of the 100 cases, Her2 overexpression (score 3+) was detected in 2 cases (2%), score 2 + in 10 cases (10%), score 1 + in 12 cases (12%), and score 0 in 76 cases (76%). The two positive cases were one adenocarcinoma and one squamous cell carcinoma; both patients were elderly male smokers. No significant association was identified between Her2 expression and age, gender, smoking, histological subtype, grade, stage, tumor size, and lymph node status. Our findings also showed no association between Her2 expression and survival; however, advanced tumor stages and positive lymph node metastasis were significantly associated with poor overall survival. All cases tested for the Her2 mutation were negative.

Conclusions

Her2 overexpression is uncommon in NSCLC among the Jordanian population. However, when the same scoring criteria are used, the rates are similar to other results found in Asian cohorts. Due to our study’s relatively small sample size, a larger one is required to investigate the prognostic value and the molecular associations between the different Her2 alterations.
Tonsillectomy reduces the family impact of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome and improves health-related quality of life in affected children
Authors: Rydenman Karin , Sparud-Lundin Carina , Karlsson-Bengtsson Anna , Berg Stefan , Fasth Anders , Wekell Per
Published: June 2023

Background

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is an autoinflammatory disorder that primarily affects young children, and typically gives rise to fever episodes that recur monthly for several years. This study investigated the impact of PFAPA syndrome on the families of affected children, the health-related quality of life (HRQOL) of children with the syndrome, and how these factors were influenced by tonsillectomy.

Methods

This prospective cohort study included 24 children with typical PFAPA syndrome that were referred for tonsillectomy, of whom 20 underwent the procedure. The control group consisted of randomly selected children from the general population. Family impact and HRQOL were measured using the standardized, validated questionnaires Pediatric Quality of Life Inventory™ (PedsQL™) Family Impact Module (FIM) and PedsQL™ 4.0 Generic Core Scales (GCS). Parents to children with PFAPA completed the questionnaires before and 6 months after their child underwent tonsillectomy, and HRQOL was measured both between and during PFAPA episodes. The Wilcoxon signed-rank test was used to compare data before and after tonsillectomy in the patient group, while the Mann–Whitney test was used for comparison of the patient and control groups.

Results

Before tonsillectomy, children with PFAPA had significantly lower scores than the control group on the PedsQL™ FIM and the PedsQL™ 4.0 GCS during fever episodes. After tonsillectomy, all patients improved with diminished febrile episodes, which resulted in significantly higher scores regarding both family impact and HRQOL at the time of follow-up. HRQOL of in children with PFAPA improved after tonsillectomy even when compared to afebrile intervals before the procedure. The differences between PFAPA patients and controls were eliminated after tonsillectomy.

Conclusion

PFAPA syndrome has a profound negative impact on the families of affected children. Tonsillectomy that leads to cessation or reduction of fever episodes eases the impact of the disease on the family. HRQOL in children with PFAPA is low during febrile episodes and similar to healthy controls in between episodes. The improvement of HRQOL in patients with PFAPA after tonsillectomy compared to the afebrile intervals before tonsillectomy highlights that the constantly recurring fevers may affect the children’s well-being even between fever episodes.
A benchmark of computational pipelines for single-cell histone modification data
Authors: Raimundo Félix , Prompsy Pacôme , Vert Jean-Philippe , Vallot Céline
Published: June 2023

Background

Single-cell histone post translational modification (scHPTM) assays such as scCUT&Tag or scChIP-seq allow single-cell mapping of diverse epigenomic landscapes within complex tissues and are likely to unlock our understanding of various mechanisms involved in development or diseases. Running scHTPM experiments and analyzing the data produced remains challenging since few consensus guidelines currently exist regarding good practices for experimental design and data analysis pipelines.

Results

We perform a computational benchmark to assess the impact of experimental parameters and data analysis pipelines on the ability of the cell representation to recapitulate known biological similarities. We run more than ten thousand experiments to systematically study the impact of coverage and number of cells, of the count matrix construction method, of feature selection and normalization, and of the dimension reduction algorithm used. This allows us to identify key experimental parameters and computational choices to obtain a good representation of single-cell HPTM data. We show in particular that the count matrix construction step has a strong influence on the quality of the representation and that using fixed-size bin counts outperforms annotation-based binning. Dimension reduction methods based on latent semantic indexing outperform others, and feature selection is detrimental, while keeping only high-quality cells has little influence on the final representation as long as enough cells are analyzed.

Conclusions

This benchmark provides a comprehensive study on how experimental parameters and computational choices affect the representation of single-cell HPTM data. We propose a series of recommendations regarding matrix construction, feature and cell selection, and dimensionality reduction algorithms.
The regulatory role and mechanism of lncTUG1 on cartilage apoptosis and inflammation in osteoarthritis
Authors: Liu Nan-nan , Huang Yan-ping , Shao Yu-bao , Fan Xue-fei , Sun He-yan , Wang Tao-rong , Yao Tao , Chen Xiao-Yu
Published: June 2023

Abstracts

Background

Long-stranded non-coding RNA TUG1 is lowly expressed in osteoarthritic chondrocytes. This study aimed to elucidate the role of TUG1 in osteoarthritic cartilage damage and the underlying mechanisms.

Methods

Combined database analysis, using primary chondrocytes as well as the C28/I2 cell line, was performed by qRT-PCR, Western blotting, and immunofluorescence to determine the expression of TUG1, miR-144-3p, DUSP1, and other target proteins. Dual luciferase reporter gene and RIP to verify direct interaction of TUG1 with miR-144–3-p and miR-144–3-p with DUSP1, Annexin V-FITC/PI double staining to detect apoptosis. CCK-8 to detect cell proliferation. The biological significance of TUG1, miR-144-3p, and DUSP1 was assessed in vitro experiments using siRNA for TUG1, mimic and repressor for miR-144-3p, and overexpression plasmid for DUSP1. In this study, all data were subjected to at-test or one-way analysis of variance with ap-value < 0.05 as the cutoff.

Results

TUG1 expression was closely associated with osteoarthritic chondrocyte damage, and knockdown of TUG1 significantly promoted chondrocyte apoptosis and inflammation. In the present study, we found that TUG1 inhibited chondrocyte apoptosis and inflammation by competitively binding miR-144-3p, deregulating the negative regulatory effect of miR-144-3p on DUSP1, promoting DUSP1 expression, and inhibiting the p38 MAPK signaling pathway.

Conclusions

In conclusion, our study clarifies the role of the ceRNA regulatory network of TUG1/miR-144-3p/DUSP1/P38 MAPK in OA cartilage injury and provides an experimental and theoretical basis for genetic engineering tools to promote articular cartilage repair.

Graphical abstract
RETRACTED ARTICLE: Associations of composite dietary antioxidant index with cardiovascular disease mortality among patients with type 2 diabetes
Authors: Yang Chan , Yang Qiangfei , Peng Xi , Li Xinqiong , Rao Guocheng
Published: June 2023

To investigate the associations of composite dietary antioxidant index (CDAI) with risk of cardiovascular disease (CVD) mortality among individuals with type 2 diabetes (T2D). This prospective cohort study included 7551 patients with T2D who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2018. Death statistics were gathered by connecting the cohort database to the National Death Index through December 31, 2019. Multivariable Cox proportional hazards regression models were utilized to calculate hazard ratios and 95% CIs for the relationship of CDAI with risks of CVD and all-cause mortality. Three multivariable models were built. Restricted cubic spline analyses were utilized to explore the nonlinear association of CDAI with CVD mortality, and nonlinearity was tested by the likelihood ratio test. This cohort study included data from 7551 participants with T2D (mean [SE] age, 61.4 (0.2) years; 3811 male [weighted, 50.5%] and 3740 female [weighted, 49.5%]; median CDAI level, − 2.19 [IQR, − 2.19 ~ − 0.22]). A total of 2227 all-cause deaths and 746 CVD deaths were identified during an average of 98 months of follow-up. Nonlinear associations were observed for CDAI (P < 0.05 for nonlinearity) with risk of CVD mortality among patients with T2D. Compared with participants in the first quartile of CDAI levels (< − 2.19), the hazard ratios for CVD mortality were 0.47 (95% CI 0.30–0.75) for participants in the highest CDAI level quartile. This cohort study found that higher CDAI levels were significantly associated with lower risk of CVD mortality among individuals with T2D.
Extreme thermal stability of the antiGFP nanobody – GFP complex
Authors: Kakasi Balázs , Gácsi Eszter , Jankovics Hajnalka , Vonderviszt Ferenc
Published: June 2023

Objective

The green fluorescent protein (GFP) and its derivatives are widely used in biomedical research. The manipulation of GFP-tagged proteins by GFP-specific binders, e.g. single-domain antibodies (nanobodies), is of increasing significance. It is therefore important to better understand the properties of antiGFP-GFP interaction in order to establish methodological applications. In this work the interaction of superfolder GFP (sfGFP) and its enhancer nanobody (aGFPenh) was characterized further.

Results

Previous calorimetric experiments demonstrated that the aGFPenh nanobody binds strongly to sfGFP with a nanomolar affinity. Here we show that this interaction results in a substantial structural stabilization of aGFPenh reflected in a significant increase of its melting temperature by almost 30 °C. The thermal stability of the sfGFP-aGFPenh complex is close to 85 °C in the pH range 7.0–8.5. For therapeutic applications thermoresistance is often an essential factor. Our results suggest that methodologies based on GFP-aGFP interaction can be applied under a wide range of physicochemical conditions. The aGFPenh nanobody seems to be suitable for manipulating sfGFP-labeled targets even in extreme thermophilic organisms.
Discriminating two bacteria via laser-induced breakdown spectroscopy and artificial neural network
Authors: Arabi Dina , Hamdy Omnia , Mohamed Mahmoud S. M. , Abdel-Salam Zienab , Abdel-Harith Mohamed
Published: June 2023

Rapid and successful clinical diagnosis and bacterial infection treatment depend on accurate identification and differentiation between different pathogenic bacterial species. A lot of efforts have been made to utilize modern techniques which avoid the laborious work and time-consuming of conventional methods to fulfill this task. Among such techniques, laser-induced breakdown spectroscopy (LIBS) can tell much about bacterial identity and functionality. In the present study, a sensitivity-improved version of LIBS, i.e. nano-enhanced LIBS (NELIBS), has been used to discriminate between two different bacteria (Pseudomonas aeruginosa and Proteus mirabilis) belonging to different taxonomic orders. Biogenic silver nanoparticles (AgNPs) are sprinkled onto the samples’ surface to have better discrimination capability of the technique. The obtained spectroscopic results of the NELIBS approach revealed superior differentiation between the two bacterial species compared to the results of the conventional LIBS. Identification of each bacterial species has been achieved in light of the presence of spectral lines of certain elements. On the other hand, the discrimination was successful by comparing the intensity of the spectral lines in the spectra of the two bacteria. In addition, an artificial neural network (ANN) model has been created to assess the variation between the two data sets, affecting the differentiation process. The results revealed that NELIBS provides higher sensitivity and more intense spectral lines with increased detectable elements. The ANN results showed that the accuracy rates are 88% and 92% for LIBS and NELIBS, respectively. In the present work, it has been demonstrated that NELIBS combined with ANN successfully differentiated between both bacteria rapidly with high precision compared to conventional microbiological discrimination techniques and with minimum sample preparation.
Comparison of MI-oriented versus CBT-oriented adjunctive treatments: impacts on therapeutic alliance and patient engagement during hospital treatment for an eating disorder
Authors: Mills Jennifer S. , Poulin Lauren E. , Kirsh Gillian
Published: June 2023

Background

Our aim was to compare MI-oriented versus CBT-oriented adjunctive treatments to test whether an MI approach is superior in terms of improving therapeutic alliance and engagement among individuals with an eating disorder. The current study was a pilot randomized controlled trial with random allocation to either MI-oriented or a CBT-oriented adjunctive treatment group completed concurrently with a hospital-based group program for adults. Both adjunctive treatment conditions consisted of three individual therapy sessions and a self-help manual.

Methods

Sixty-five outpatients receiving hospital treatment for a diagnosed eating disorder were randomly assigned to a treatment group. Measures of working therapeutic alliance, engagement, treatment completion, and clinical impairment were completed at preadmission, mid-treatment, and at the end of treatment.

Results

Working alliance increased equivalently in both conditions over time in treatment. Similarly, there were no differences between conditions in terms of engagement. Regardless of therapy orientation, greater use of the self-help manual predicted lowered eating disorder risk; stronger patient ratings of therapeutic alliance predicted decreased feelings of both ineffectiveness and interpersonal problems.

Conclusion

This pilot RCT provides further evidence that both alliance and engagement are important for treatment of an eating disorder; however, there was no clear advantage of MI over CBT as an adjunctive treatment approach to improving alliance or engagement.

Trial registration: ClinicalTrials.gov ID #NCT03643445 (proactive registration).
GIS-based inventory for safeguarding and promoting Portuguese glazed tiles cultural heritage
Authors: Santos Bertha , Gonçalves Jorge , Almeida Pedro G. , Martins-Nepomuceno Ana M. T.
Published: June 2023

Innovative, non-invasive, digital, and cost-effective instruments for systematic inventory, monitoring and promotion are a valuable resource for managing tangible and intangible cultural heritage. Due to its powerful and effective inventory and analysis potential, which allows supporting central and local entities responsible for cultural heritage management, Geographic Information Systems (GIS) have proven to be an appropriate information technology for developing these kinds of instruments. Given the above, this work aims to introduce a GIS-based instrument to support inventorying, safeguarding, tourism, and cultural promotion of the traditional Portuguese glazed tile (‘azulejo’, in Portuguese) to raise general awareness of the importance of this unique Portuguese heritage. To the best of the authors’ knowledge, there is no other instrument available with inventory and safeguarding management functions that is accessible and affordable, developed to be used at a municipal level and that contributes to the enrichment of the cultural and tourist information. Information from 70 tile works located in the Portuguese city of Covilhã was used to test the proposed GIS tool, resulting in a georeferenced alphanumeric, graphical, image and drawing inventory and in three pedestrian routes for touristic and cultural heritage promotion. The results were validated by both the research team and the municipality of Covilhã, foreseeing its expansion and daily use in the management of the heritage of the traditional Portuguese glazed tile. The proposed instrument can be replicated in other locations and easily implemented and managed by municipalities or institutions dealing with the protection of cultural heritage.
Highly sensitive ultrasound detection using nanofabricated polymer micro-ring resonators
Authors: Lee Youngseop , Zhang Hao F. , Sun Cheng
Published: June 2023

Photoacoustic (PA) imaging enables noninvasive volumetric imaging of biological tissues by capturing the endogenous optical absorption contrast. Conventional ultrasound detectors using piezoelectric materials have been widely used for transducing ultrasound signals into the electrical signals for PA imaging reconstruction. However, their inherent limitations in detection bandwidth and sensitivity per unit area have unfortunately constrained the performance of PA imaging. Optical based ultrasound detection methods emerge to offer very promising solutions. In particular, polymer micro-ring resonators (MRRs) in the form of integrated photonic circuits (IPC) enable significant reduction for the sensing area to 80 μm in diameter, while maintaining highly sensitive ultrasound detection with noise equivalent pressure (NEP) of 0.49 Pa and a broad detection frequency range up to 250 MHz. The continued engineering innovation has further transformed MRRs to be transparent to the light and thus, opens up a wide range of applications, including multi-modality optical microscope with isometric resolution, PA endoscope, photoacoustic computed tomography (PACT), and more. This review article summarizes and discusses the evolution of polymer MRR design and the associated nanofabrication process for improving the performance of ultrasound detection. The resulting novel imaging applications will also be reviewed and discussed.
Acute disseminated encephalomyelitis with optic neuritis and mononeuritis multiplex following COVID-19 vaccination: case report
Authors: Chittilappilly Jomal Mathew , Kaitharath Sholy Vareed
Published: June 2023

Background

Acute disseminated encephalomyelitis (ADEM) is an extremely rare complication of COVID-19 vaccination with very few reports worldwide. Concomitant peripheral nervous tissue involvement in ADEM is very uncommon.

Case presentation

We report the case of a 52 year aged lady who developed headache and focal neurological deficits after 10 days of COVID-19 vaccination. Her evaluation suggested ADEM with optic neuritis and mononeuritis multiplex. She responded to pulse methylprednisolone therapy.

Conclusions

COVID-19 vaccine may be associated with ADEM, optic neuritis and concurrent peripheral nervous system inflammation in rare instances.
A G-type lectin receptor-like kinase in Nicotiana benthamiana enhances resistance to the fungal pathogen Sclerotinia sclerotiorum by complexing with CERK1/LYK4
Authors: Pi Lei , Zhang Yifan , Wang Jinghao , Wang Nan , Yin Zhiyuan , Dou Daolong
Published: June 2023

Fungal pathogens are among the main destructive microorganisms for crops and ecosystems worldwide, causing substantial agricultural and economic losses. Plant cell surface-localized lysin motif (LysM)-containing receptor-like kinases (RLKs) or receptor-like proteins (RLPs) enhance plant resistance to fungal pathogens via sensing chitin, which is a conserved component of the fungal cell wall. Other types of RLKs also regulate chitin signaling via distinct mechanisms in plants. In this study, we identified a G-type lectin RLK, NbERK1, which positively regulated chitin signaling and resistance to the fungal pathogen Sclerotinia sclerotiorum in the model plant Nicotiana benthamiana. In addition, the LysM-RLK NbCERK1/NbLYK4 was shown to mediate plant resistance to S. sclerotiorum positively. Further, the association of chitin-induced NbCERK1-NbLYK4 was found to be essential for chitin perception and signaling. Importantly, NbERK1 was associated with NbCERK1/NbLYK4 and positively regulated chitin-induced NbCERK1-NbLYK4 association. Moreover, chitin could induce the dissociation of NbERK1 from the NbCERK1-NbLYK4 complex. Also, the kinase activity of NbERK1 was likely essential for this dissociation and plant resistance-enhancing activity of NbERK1. Together, these results suggest that NbERK1 is a novel component of the chitin receptor complex and enhances plant resistance to fungal pathogens via regulating chitin signaling.
Characterizing hydraulic fracture growth using distributed acoustic sensing-recorded microseismic reflections
Authors: Ma Yuanyuan , Eaton David W. , Wang Chaoyi , Aklilu Alemayehu
Published: June 2023

Hydraulic fracturing is crucial for enhancing hydrocarbon production from unconventional reservoirs. The characterization of fracture geometry and propagation has significant value in understanding reservoir response and designing more efficient completions. Distributed acoustic sensing (DAS) is a rapidly developing technology that can be used for this purpose because it provides wide-aperture observations of microseismic wavefields that contain direct P and S arrivals as well as converted and reflected waves. In addition to traditional approaches for microseismic event location and source mechanism analysis, the high spatial resolution of DAS microseismic recordings allows the imaging of induced fractures with reflected waves. Reflections are generated by waves radiated from microseismic events that impinge on hydraulic fractures created during prior treatment stages. We use a straightforward method based on f- k filtering and ray tracing to map reflected S waves from the time domain to reflectivity in the space domain. A case study of fracture imaging indicates that inferred fracture development, based on reflection imaging, is consistent with fracture-driven interactions observed using low-frequency DAS (LF-DAS) data. In addition, this study reveals reflection images of apparent distal fractures that do not reach the fiber and thus are not directly observed by LF-DAS. Fracture images obtained from several microseismic events during the same stage provide the opportunity to observe snapshots of dynamic fracture evolution processes.
Quantum algorithm for the covariance matrix preparation and its application
Authors: Ning T. , Yang Y. L.
Published: June 2023

Performing the eigendecomposition of the covariance matrix of the dataset is of great significance in the field of machine learning. However, classical operations will become time-consuming when involving large data sets. In this paper, in order to address this problem, we design an efficient quantum algorithm to prepare the covariance matrix state by means of quantum amplitude estimation. After that, we research on its application in principal component analysis and Mahalanobis distance calculation. Specifically, we obtain the transformation matrix for quantum principal component analysis based on the singular value estimation algorithm and the amplitude amplification algorithm. Furthermore, we invoke the quantum matrix inversion algorithm to calculate the Mahalanobis distance. The final complexity analysis shows that our proposed algorithms can achieve speedup compared to their classical counterparts under certain conditions.
Phenotypic Profiling and Molecular Mechanisms in Hyperparathyroidism-jaw Tumor Syndrome
Authors: Tora Rana , Welch James , Sun Jian , Agarwal Sunita K , Bell Debra A , Merino Maria , Weinstein Lee S , Simonds William F , Jha Smita
Published: June 2023

Context

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism caused by germline inactivating mutations in CDC73 encoding parafibromin and is associated with an increased risk of parathyroid cancer. There is little evidence to guide the management of patients with the disease.

Objective

(1) Characterize the natural history of HPT-JT, (2) correlate genotype and histology of parathyroid tumors with parafibromin immunostaining, (3) understand molecular changes downstream to CDC73 loss.

Design

Retrospective study of patients with HPT-JT syndrome (genetically confirmed or affected first-degree relatives). Independent review of uterine tumor from 2 patients and staining for parafibromin on parathyroid tumors from 19 patients (13 adenomas, 6 carcinomas) was performed. RNA-sequencing was performed in 21 parathyroid samples (8 HPT-JT-related adenomas, 6 HPT-JT-related carcinomas, and 7 sporadic carcinomas with wild-type CDC73).

Results

We identified 68 patients from 29 kindreds with HPT-JT with median age at last follow-up of 39 [interquartile range, 29-53] years. A total of 55/68 (81%) developed primary hyperparathyroidism; 17/55 (31%) had parathyroid carcinoma. Twelve of 32 (38%) females developed uterine tumors. Of the 11 patients who had surgical resection for uterine tumors, 12/24 (50%) tumors were rare mixed epithelial mesenchymal polypoid lesions. Four of 68 patients (6%) developed solid kidney tumors; 3/4 had a CDC73 variant at p.M1 residue. Parafibromin staining of parathyroid tumors did not correlate with tumor histology or genotype. RNA-sequencing showed a significant association of HPT-JT-related parathyroid tumors with transmembrane receptor protein tyrosine kinase signaling pathway, mesodermal commitment pathway, and cell-cell adhesion.

Conclusions

Multiple, recurrent atypical adenomyomatous uterine polyps appear to be enriched in women with HPT-JT and appear characteristic of the disease. Patients with CDC73 variants at p.M1 residue appear predisposed to kidney tumors.

Clinical Trial number

NCT04969926
Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy
Authors: Dineen Rosemary A , Martin-Grace Julie , Ahmed Khalid Mohamed Saeed , Taylor Angela E , Shaheen Fozia , Schiffer Lina , Gilligan Lorna C , Lavery Gareth G , Frizelle Isolda , Gunness Anjuli , Garrahy Aoife , Hannon Anne Marie , Methlie Paal , Eystein Sverre Husebye , Stewart Paul M , Tomlinson Jeremy W , Hawley James M , Keevil Brian G , O’Reilly Michael W , Smith Diarmuid , McDermott John , Healy Marie-Louise , Agha Amar , Pazderska Agnieszka , Gibney James , Behan Lucy-Ann , Thompson Chris J , Arlt Wiebke , Sherlock Mark
Published: June 2023

Background

Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo.

Study Design and Methods

Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls.

Results

Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue.

Conclusion

Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC.
Transcriptional bursting: stochasticity in deterministic development
Authors: Leyes Porello Emilia A. , Trudeau Robert T. , Lim Bomyi
Published: June 2023

The transcription of DNA by RNA polymerase occurs as a discontinuous process described as transcriptional bursting. This bursting behavior is observed across species and has been quantified using various stochastic modeling approaches. There is a large body of evidence that suggests the bursts are actively modulated by transcriptional machinery and play a role in regulating developmental processes. Under a commonly used two-state model of transcription, various enhancer-, promoter- and chromatin microenvironment-associated features are found to differentially influence the size and frequency of bursting events – key parameters of the two-state model. Advancement of modeling and analysis tools has revealed that the simple two-state model and associated parameters may not sufficiently characterize the complex relationship between these features. The majority of experimental and modeling findings support the view of bursting as an evolutionarily conserved transcriptional control feature rather than an unintended byproduct of the transcription process. Stochastic transcriptional patterns contribute to enhanced cellular fitness and execution of proper development programs, which posit this mode of transcription as an important feature in developmental gene regulation. In this Review, we present compelling examples of the role of transcriptional bursting in development and explore the question of how stochastic transcription leads to deterministic organism development.
Host species differences in the thermal mismatch of host–parasitoid interactions
Authors: Malinski Katherine H. , Sorenson Clyde E. , Moore M. Elizabeth , Willett Christopher S. , Kingsolver Joel G.
Published: June 2023

Extreme high temperatures associated with climate change can affect species directly, and indirectly through temperature-mediated species interactions. In most host–parasitoid systems, parasitization inevitably kills the host, but differences in heat tolerance between host and parasitoid, and between different hosts, may alter their interactions. Here, we explored the effects of extreme high temperatures on the ecological outcomes – including, in some rare cases, escape from the developmental disruption of parasitism – of the parasitoid wasp, Cotesia congregata, and two co-occurring congeneric larval hosts, Manduca sexta and M. quinquemaculata. Both host species had higher thermal tolerance than C. congregata, resulting in a thermal mismatch characterized by parasitoid (but not host) mortality under extreme high temperatures. Despite parasitoid death at high temperatures, hosts typically remain developmentally disrupted from parasitism. However, high temperatures resulted in a partial developmental recovery from parasitism (reaching the wandering stage at the end of host larval development) in some host individuals, with a significantly higher frequency of this partial developmental recovery in M. quinquemaculata than in M. sexta. Hosts species also differed in their growth and development in the absence of parasitoids, with M. quinquemaculata developing faster and larger at high temperatures relative to M. sexta. Our results demonstrate that co-occurring congeneric species, despite shared environments and phylogenetic histories, can vary in their responses to temperature, parasitism and their interaction, resulting in altered ecological outcomes.
Adherence to Extended Venous Thromboembolism Prophylaxis and Outcomes After Complex Gastrointestinal Oncologic Surgery
Authors: Mavros Michail N. , Johnson Lauren A. , Schootman Mario , Orcutt Sonia T. , Peng Cheng , Martin Bradley C.
Published: June 2023

Background

Clinical guidelines recommend extended venous thromboembolism (VTE) prophylaxis for cancer patients after major gastrointestinal (GI) operations. However, adherence to the guidelines has been low, and the clinical outcomes not well defined.

Methods

This study retrospectively analyzed a random 10 % sample of the 2009–2022 IQVIA LifeLink PharMetrics Plus database, an administrative claims database representative of the commercially insured population of the United States. The study selected cancer patients undergoing major pancreas, liver, gastric, or esophageal surgery. The primary outcomes were 90-day post-discharge VTE and bleeding.

Results

The study identified 2296 unique eligible operations. During the index hospitalization, 52 patients (2.2 %) experienced VTE, 74 patients (3.2 %) had postoperative bleeding, and 140 patients (6.1 %) had a hospital stay of at least 28 days. The remaining 2069 operations comprised 833 pancreatectomies, 664 hepatectomies, 295 gastrectomies, and 277 esophagectomies. The median age of the patients was 49 years, and 44 % were female. Extended VTE prophylaxis prescriptions were filled for 176 patients (10.4 % for pancreas, 8.1 % for liver, 5.8 % for gastric cancer, and 6.5 % for esophageal cancer), and the most used agent was enoxaparin (96 % of the patients). After discharge, VTE occurred for 5.2 % and bleeding for 5.2 % of the patients. The findings showed no association of extended VTE prophylaxis with post-discharge VTE (odds ratio [OR], 1.54; 95 % confidence interval [CI], 0.81–2.96) or bleeding (OR, 0.72, 95 % CI, 0.32–1.61).

Conclusions

The majority of the cancer patients undergoing complex GI surgery did not receive extended VTE prophylaxis according to the current guidelines, and their VTE rate was not higher than for the patients who received it.
Digital transformation of organizations and their organizational cultures. A case study in a national defense industry
Authors: Kapotas Spyridon
Published: June 2023

Digital transformation has become vital for organizations in order for them to differentiate from competitors providing a competitive advantage in the fast-changing environment they operate. Digital transformation is considered as a radical transformation affecting organization’s products, services, people and processes while improving performance. It is a risky and tremendous challenge for most organizations. Based on a dissertation with the current paper an approach on digital transformation, in a national defense company is attempted. Products and services provided are characterized through high quality standards and a strong culture. Those characteristics are considered a fruitable ground for providing a framework to transform an organization into a digital one. Taking into consideration the above, literature research on digital transformation of organizations and their benefits are provided. The digitalization process is analyzed in order to show the building blocks of transforming the organization into a digital one. However, in order to start such a process, the organization has to have an adaptive high performance organization culture. This is considered as the base to start the digitalization process. In order for the organization to have such a culture, current situation has to be assessed and certain actions to be taken. An assessment of above-mentioned company is presented and actions proposed. It is obvious that organizational digital transformation is inextricably linked with an organizational culture change. The benefits and barriers from such a transformation are shown and finally proposals presented regarding a digital strategy implementation as well as a vision and mission statement for the company.

EL Classifications: M14.

Key words: Digital transformation, digitalization process, digital strategy, organizational culture change, vision and mission statement
The Impact of COVID – 19 First Outbreak on Greek Private High Schools & The Distance Learning Experience
Authors: Malagkoniari Maria , Deliou Cleopatra
Published: June 2023

Although when we speak of COVID – 19 the main affect concerns the health of individuals, it is clear that the pandemic has also affected many aspects of life such as the educational sector. Both teachers and students in Greece faced the challenge of the implementation of distance learning, national wide, during the pandemic.

There is still a lack of a proper theoretical model and comprehensive scientific tools to measure the impact of COVID – 19 in education. The purpose of this research is to study and analyze whether distance learning affected the Greek private high schools in different ways such as in terms of students’ graduation or their success rate in the PanHellenic Exams, during the first outbreak of the COVID-19 pandemic.

Based on literature and feedback received from high schools’ principals we captured important results over the use of distance learning and its effectiveness. More specifically, through the quantitative study performed on 63 out of 79 private high schools’ principals, the researchers reached the conclusion that the majority of private schools managed distance education successfully. It was proved that both teaching and administrative staff were highly competent and skilled in the use of new technologies and therefore, distance education was not treated as a problematic situation but it steadily became part of each school’s daily routine.

 

EL Classifications: Μ19 (M: Business Administration and Business Economics/ Marketing/ Accounting/ Personnel Economics – Μ1: Business Administration – M19: Others)

 

Key words: Distance Education, COVID – 19 Pandemic, Greek Private High Schools, Principals