bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of exposure to needle stick and sharp‐related injury and status of hepatitis B vaccination among healthcare workers: A cross‐sectional study
Authors: Rupak K. C. , Khadka Dipendra , Ghimire Sabal , Bist Aayush , Patel Ishant , Shahi Smriti , Dhakal Natasha , Tiwari Ibeja , Shrestha Dhan B.
Published: July 2023

Background and Aims

Hepatitis B is a leading cause of chronic liver disease and subsequent liver transplantation. This is a vaccine‐preventable illness. Health workers continue to be at risk for blood‐borne pathogens due to occupational exposures. The overall goals of our study were to determine the prevalence of exposure to needle sticks and sharp‐related injuries (NSSI) and hepatitis B vaccination status among healthcare workers (HCWs) of Nepalgunj Medical College Teaching Hospital (NGMCTH), Kohalpur, Banke, Nepal.

Methods

A descriptive cross‐sectional study was conducted among HCWs at the NGMCTH following ethics approval by the NGMCTH Ethics Review Committee. A pretested structured questionnaire was used to compile the data. Data was collected from September 15, 2021 to September 14, 2022. Collected data entered in Microsoft Excel and analyzed using statistical package for social sciences version 22. Analyzed data were presented using simple descriptive statistics with appropriate figures and tables.

Results

A total of 304 among 506 HCWs (60.1%) participated in the survey were exposed to Needle sticks. Nine of whom (3.7%) were injured substantially (more than 10 times). Among nursing students, 21.3% had experience with NSSI. 71.7% of HCWs had received at least one dose of the hepatitis B vaccine, of whom 61.9% (44.5% of total HCWs) had received three doses.

Conclusions

This study demonstrated that more than two‐quarters of HCWs were exposed to NSSI. Despite being at risk, vaccination status was still low, and less than half only received three complete doses. Precaution should be taken when working with instrumentation and procedures. Hepatitis B immunization programs for HCWs should be delivered at no cost with 100% coverage and protection. Raising awareness about hepatitis B infection and immunization remains crucial to primary prevention.
Use of covariance matrix images for electroencephalography signal classification for multiclass motor imagery‐based brain computer interface
Authors: Thrikkannoor Kolathod Muhamed Jishad , Sanjay M.
Published: July 2023

Electroencephalogram (EEG) signals can be used to control devices using brain computer interface (BCI) systems, which offer assistance to patients with neuromuscular diseases. This article aims to determine the feasibility of using spatial covariance matrices with deep convolutional neural networks for multiclass motor imagery (MI) task classification for EEG‐based BCIs. Covariance matrices derived from multichannel EEG data are converted into color‐scaled images, which are used to train the AlexNet neural network using transfer learning. Samples of 2‐s duration are extracted every 200 ms intervals from each MI activity EEG eventually increasing the training data size sixfold and reducing the latency in real‐time implementations. Observed the performance using two popular publicly available BCI datasets for two‐class and four‐class MI classification. BCI competition IV Dataset IIa has shown average accuracy of 93.99% (k = 0.88) for two‐class and 86.70% (k = 0.82) for four‐class MI classification. BCI competition III Dataset IVa exhibited average accuracy of 97.02% (k = 0.94) for two‐class classification. Good performance was observed for training with cross‐subject data for two‐class and four‐class classification. The proposed method has shown improved accuracy for multiclass MI classification compared with existing works. The CNN is able to extract features from the covariance matrix and classify the MI data with reasonable accuracy. Since this method can handle large‐dimension data, dimension reduction, and source separation techniques are not required.
Evaluation of immunotoxicity of sodium metavanadate following drinking water exposure in female B6C3F1/N mice in a 28‐day study
Authors: Frawley Rachel , Johnson Victor J. , Burleson Gary R. , Shockley Keith R. , Cesta Mark F. , Travlos Greg , Cora Michelle , Roberts Georgia , Germolec Dori
Published: July 2023

Sodium metavanadate (NaVO3) is a pentavalent vanadium compound used in the metal industry and dietary supplements; human exposure occurs through inhalation of fumes and dust and ingestion of NaVO3‐containing products. The objective of this study was to assess the potential immunotoxicity of NaVO3. Female B6C3F1/N mice were exposed to 0–500 ppm NaVO3in drinking water for 28 days and evaluated for effects on immune cell populations and innate, cellular‐mediated, and humoral‐mediated immunity. There was a decreasing trend in body weight (BW) and BW gain in NaVO3exposed mice, with a decrease (p ≤ 0.05) in BW gain at ≥250 ppm, relative to control. Conversely, increasing trends in spleen weights and an increase (p ≤ 0.05) in the spleen:BW ratio at ≥250 ppm NaVO3were observed. NaVO3exposure altered antibody production against sheep red blood cells (SRBC). Antibody forming cells (AFC)/106spleen cells exhibited a decreasing trend, with a decrease (p ≤ 0.05) at 500 ppm NaVO3, concurrent with an increase in percent B cells. NaVO3had no effect on the serum anti‐SRBC IgM antibody titers or anti‐keyhole limpet hemocyanin antibody production. Exposure to NaVO3decreased the percentage of natural killer cells at all dose levels (p ≤ 0.05), with no effect on the lytic activity. NaVO3altered T‐cell populations at 500 ppm but had no effect on T‐cell proliferative responses or the lytic activity of cytotoxic T cells. Collectively, these data indicate that NaVO3exposure can adversely affect the immune system by inducing alterations in humoral‐mediated immunity, specifically the AFC response, with no effect on cell‐mediated or innate immunity.
Effective sanction avoidance in drug trafficking: The construction and validation of the restrictive deterrence utility scale using a sample of female drug offenders
Authors: Guan Xin , Lo T. Wing
Published: July 2023

Drug traffickers perform many crime strategies to avoid legal sanctions. The use of any crime strategy is mainly for reducing the risk of arrest, which has been the focus of research on restrictive deterrence. This study aims to develop a Restrictive Deterrence Utility Scale (RDUS) to measure the effectiveness of crime strategies used in drug trafficking. Survey data were collected from August to October 2021, including 294 female drug offenders aged between 21 and 61 years serving sentences with a median length of around 10 years in a Southern city in Mainland China. Exploratory and confirmatory factor analysis was conducted for scale investigation. Three valid and reliable factors for the RDUS were found: anomaly avoidance, reduction of exposure time, and the use of weapons and tools. Composite reliability, convergent validity, discriminant validity of three factors were confirmed with Cronbach α being higher than 0.9, that being higher than correspondent Average Variance Extracted which all being higher than 0.5 and higher than correspondent factor correlation. The RDUS offers a helpful method for assessing the motivation for drug traffickers to persist in drug crime and for formulating appropriate interventions for drug prohibition.
Postpandemic rebound of adeno‐associated virus type 2 (AAV2) infections temporally associated with an outbreak of unexplained severe acute hepatitis in children in the United Kingdom
Authors: Gates Shannah , Andreani Julien , Dewar Rebecca , Smith Donald B. , Templeton Kate , Child Harry T. , Breuer Judy , Golubchik Tanya , Bassano Irene , Wade Matthew J. , Jeffries Aaron R. , Simmonds Peter , Harvala Heli
Published: July 2023

Over 1000 cases of unexplained severe acute hepatitis in children have been reported to date worldwide. An association with adeno‐associated virus type 2 (AAV2) infection, a human parvovirus, prompted us to investigate the epidemiology of AAV in the United Kingdom. Three hundred pediatric respiratory samples collected before (April 03, 2009–April 03, 2013) and during (April 03, 2022) the COVID‐19 pandemic were obtained. Wastewater samples were collected from 50 locations in London (August 2021–March 2022). Samples were tested for AAV using real‐time polymerase chain reaction followed by sequencing. Selected adenovirus (AdV)‐positive samples were also sequenced. The detection frequency of AAV2 was a sevenfold higher in 2022 samples compared with 2009–2013 samples (10% vs. 1.4%) and highest in AdV‐positive samples compared with negatives (10/37, 27% vs. 5/94, 5.3%, respectively). AAV2‐positive samples displayed high genetic diversity. AAV2 sequences were either very low or absent in wastewater collected in 2021 but increased in January 2022 and peaked in March 2022. AAV2 was detected in children in association with AdV of species C, with a highest frequency in 2022. Our findings are consistent with the expansion of the population of children unexposed to AAV2, leading to greater spread of the virus once distancing restrictions were lifted.
Determination of volatile profiles of woodland strawberry (Fragaria vesca) during fruit maturation by HS‐SPME GC–MS
Authors: Zheng Sujin , Cai Jingjing , Huang Peibin , Wang Yuqi , Yang Zhenbiao , Yu Yuan
Published: July 2023

BACKGROUND

Aroma is an important agronomic trait for strawberries, and the improvement of fruit flavor is a key goal in current strawberry breeding programs. Fragaria vesca (also known as woodland strawberry) has become an excellent model plant with exquisite flavor, a small genome size and a short life cycle. Thus, the comprehensive identification of fruit volatiles and their accumulation pattern of F. vesca strawberries are very important and necessary to the fruit aroma study. This study examined the volatile profile changes from the fruits of three F. vesca genotypes during maturation using headspace solid‐phase microextraction combined with gas chromatography–mass spectrometry with multivariate analysis.

RESULTS

A total of 191 putative volatile compounds were identified, while 152, 159 and 175 volatiles were detected in 20–30 DAP (days after pollination) fruits of Hawaii 4 (HW), Reugen (RG) and Yellow Wonder (YW), respectively. Aldehydes and alcohols predominated in the early time point while esters were predominant during the late time point. Ketones were the dominant compounds from F. vesca strawberries at the ripe stage. Certain genotype‐characteristic volatiles were identified, including eugenol, γ‐octalactone and δ‐decalactone only detected in YW, and mesifurane was found in HW.

CONCLUSIONS

RG and YW showed very similar volatile compositions, but YW presented a greater number of volatiles and RG yielded a higher content. Differences in the volatile composition may be primarily due to genetic relationships. The metabolic changes that occurred during fruit ripening and characteristic volatiles will be a useful reference for future studies of strawberry volatiles. © 2023 Society of Chemical Industry.
Agricultural production efficiency estimation and spatiotemporal convergence characteristic analysis in the Yangtze River Economic Belt: A semi‐parametric metafrontier approach
Authors: Guo Baishu , He Dawei , Jin Gui
Published: July 2023

The sustainable development goals regard improving agricultural production efficiency (APE) as the main method to solve food security problems. Based on the geographical cognition, combined with the functional positioning, we used meta semi‐parametric linear programming and spatial convergence models to analyze the spatiotemporal convergence characteristics of APE in the Yangtze River Economic Belt from 2000 to 2020. The results show that (1) under the framework of metafrontier analysis, the APE increases while maintaining an olive‐shaped stable structure of “sharp at both ends and wide in the middle”; (2) the efficiencies in agricultural production areas and the middle reaches has obviously declined compared with that of non‐agricultural production areas; and (3) non‐spatial factors and spatial factors jointly drive the convergence. The research results can provide references for clarifying the evolution law of regional agriculture and formulating differentiation macro policies.
Computational study unravels inhibitory potential of epicatechin gallate against inflammatory and pyroptosis‐associated mediators in COVID‐19
Authors: Rajak Prem , Ganguly Abhratanu
Published: July 2023

Coronavirus disease‐19 (COVID‐19) is the global health emergency caused by SARS‐CoV‐2. Upon infection, antigenic determinants of the virus trigger massive production of proinflammatory/pyroptosis‐associated proteins, resulting in cytokine storm, tissue damage, and multiorgan failure. Therefore, these proinflammatory/pyroptosis‐associated mediators are promising therapeutic targets to combat COVID‐19. Epicatechin gallate (ECG) is a polyphenol found in green tea. It has antioxidative and anti‐inflammatory properties. Hence, in the present study, ECG was selected to explore its binding potential for inflammatory mediators such as interleukins, interferon‐γ (IFNγ), and tumor necrosis factor‐α (TNF‐α), along with their native receptors. In addition, the interacting potential of ECG with pyroptosis‐associated proteins, viz. caspases and BAX has also been investigated. Molecular docking analysis has revealed that ECG interacts with interleukins, IFNγ, TNF‐α, cytokine receptors, caspase‐1/4/11, and BAX with significant binding affinity. Several amino acid residues of these mediators were blocked by ECG through stable hydrogen bonds and hydrophobic contacts. ECG interacted with caspase‐11, BAX, and TNF‐R1 with better binding affinities. Therefore, the present in silico study indicates that ECG could be a potential drug to subvert cytokine storm and pyroptosis during COVID‐19.
Examination of Predictors of Pain at 12 Months Postdiagnosis in Head and Neck Cancer Survivors
Authors: Howren M. Bryant , Seaman Aaron , Super Grace L. , Christensen Alan J. , Pagedar Nitin A.
Published: July 2023

Objective

Pain following the completion of treatment is important but has received less attention in the head and neck cancer (HNC) literature. The present study sought to examine the prevalence and predictors of pain measured 12 months postdiagnosis and its impact on HNC‐specific health‐related quality of life (HRQOL) in 1038 HNC survivors.

Study Design

Prospective observational study.

Setting

Single‐institution tertiary care center.

Methods

Pain was measured using a single item ranging from 0 to 10 with 0 representing no pain and 10 representing the worst pain possible. Self‐reported depressive symptomatology was measured using the Beck Depression Inventory and self‐reported problem alcohol use was measured by the Short Michigan Alcoholism Screening Test. HNC‐specific HRQOL was measured using the Head and Neck Cancer Inventory (HNCI).

Results

Hierarchical multivariable linear regression analyses indicated that in addition to pain at 3 months postdiagnosis (β = .145, t = 3.18, sr2 = .019, p = .002), both depressive symptomatology (β = .110, t = 2.49, sr2 = .011, p = .015) and problem alcohol use (β = .092, t = 2.07, sr2 = .008, p = .039) were significant predictors of pain at 12 months postdiagnosis. Subgroup analyses suggest that across all 4 HNCI domains, those in the moderate and severe pain groups at 12 months postdiagnosis failed to reach 70 which is indicative of high functioning.

Conclusion

Pain in patients with HNC is a considerable issue at 12 months postdiagnosis, deserving further attention. Behavioral factors such as depression and problem alcohol use may be associated with pain and require systematic screening over time to identify and treat issues that impact optimal long‐term recovery from HNC, including disease‐specific HRQOL.
Predicting GPR40 Agonists with A Deep Learning‐Based Ensemble Model
Authors: Yang Jiamin , Jiang Chen , Chen Jing , Qin Lu‐Ping , Cheng Gang
Published: July 2023

Recent studies have identified G protein‐coupled receptor 40 (GPR40) as a promising target for treating type 2 diabetes mellitus, and GPR40 agonists have several superior effects over other hypoglycemic drugs, including cardiovascular protection and suppression of glucagon levels. In this study, we constructed an up‐to‐date GPR40 ligand dataset for training models and performed a systematic optimization of the ensemble model, resulting in a powerful ensemble model (ROC AUC: 0.9496) for distinguishing GPR40 agonists and non‐agonists. The ensemble model is divided into three layers, and the optimization process is carried out in each layer. We believe that these results will prove helpful for both the development of GPR40 agonists and ensemble models. All the data and models are available on GitHub. (https://github.com/Jiamin‐Yang/ensemble_model)
A latent profile analysis of emotional, behavioral, and social problems among victims of bullying
Authors: Balan Raluca , Dobrean Anca , Balazsi Robert , Cordier Reinie
Published: July 2023

Previous research, using a variable‐centered approach, points out to the possibility that not all victims of bullying have the same mental health and social profile. The aim of the current investigation was to explore whether there are different profiles—related to emotional, behavioral, and social problems—of pure victims of bullying and bully‐victims, respectively, by using a person‐centered approach. The analytical sample consisted of 224 children and adolescents, aged 8–17 years old (M = 14, SD = 1.97), who self‐identified as pure victim or bully‐victims. Latent profile analysis (LPA) produced the following four profiles among pure victims of bullying: (1) an asymptomatic profile; (2) a profile with high emotional problems and moderate hyperactivity; (3) a profile with high emotional problems and hyperactivity, but moderate conduct and social problems; and (4) a profile high in conduct and social problems, yet with moderate emotional problems and hyperactivity. Among bully‐victims, LPA yielded the following four profiles: (1) an asymptomatic profile; (2) a profile of high conduct, emotional and social problems, but moderate hyperactivity; (3) a profile with high hyperactivity, moderate emotional, and conduct problems; and (4) a profile characterized by high emotional, social problems, and hyperactivity. The implications, limitations, and future directions will be discussed.
Protective factors in schools after the COVID‐19 pandemic: Views of school counselors
Authors: Çetinkaya Ali , Bulut Safiye Sarıcı
Published: July 2023

This research examines the protective factors in schools after the coronavirus disease 2019 (COVID‐19) pandemic by considering the opinions of school counselors. It was carried out within the scope of phenomenology design, one of the qualitative research methods. The research was conducted in Turkey. The research data were obtained through face‐to‐face interviews with 20 school counselors who were working in public schools in the fall semester of the 2022–2023 academic year and were determined by the purposeful sampling method. The content analysis method was used to analyze the data. School counselors were asked four questions about protective factors at school, skills needed by students, and the roles of schools and teachers. According to school counselors, the school needs to create a supportive and safe atmosphere. Having skills such as coping with stress, emotion regulation, problem‐solving skills, resilience, interpersonal skills, conscious use of technology, and media literacy will increase student adaptation. According to school counselors, having features such as creating a positive atmosphere in schools, monitoring and supporting student development, cooperation, providing counseling services, and creating a safe environment is necessary. It was also emphasized that teachers should have characteristics such as unconditional acceptance, establishing close relationships, being a model, cooperation, and getting to know the student. The results obtained were discussed in light of the literature and suggestions were made.
Graphene Oxide Incorporated Zinc Oxide Thin Films by Spray Pyrolysis for Efficient Photodegradation of Methylene Blue
Authors: Paul John , Dhivyaprasath Kasinathan , Ashok Mahalingam , Chandroth Santhosh Kumar Maniyeri
Published: July 2023

Photodegradation of methylene blue dye was studied with pure and graphene oxide incorporated zinc oxide thin films as catalysts. Graphene oxide content in the precursor solution was varied from 0.0005 to 0.005 g/L. Thin films were prepared by automated spray pyrolysis technique at a substrate temperature of 425 °C. Structural studies revealed the formation of hexagonal wurtzite structure of zinc oxide. Carbon presence in the films was confirmed with energy‐dispersive spectroscopy. Optical band gap of the samples was determined using Tauc method. Intensity of the near band emission of photoluminescence spectrum was found to decrease upon increasing graphene oxide concentration. Photocatalytic activity of all the films has been studied against methylene blue dye under solar irradiation for 180 minutes and it is found that the highest graphene oxide content attributes to better degradation efficiency of 91.2 %.
Novel Semiconductive Ternary Hybrid Heterostructures for Artificial Optoelectronic Synapses
Authors: Liu Jing‐Yan , Zhang Xiang‐Hong , Fang Hua , Zhang Shu‐Quan , Chen Yong , Liao Qing , Chen Hong‐Ming , Chen Hui‐Peng , Lin Mei‐Jin
Published: July 2023

Synaptic devices that mimic biological synapses are considered as promising candidates for brain‐inspired devices, offering the functionalities in neuromorphic computing. However, modulation of emerging optoelectronic synaptic devices has rarely been reported. Herein, a semiconductive ternary hybrid heterostructure is prepared with a D‐D’‐A configuration by introducing polyoxometalate (POM) as an additional electroactive donor (D’) into a metalloviologen‐based D‐A framework. The obtained material features an unprecedented porous 8‐connected bcu‐net that accommodates nanoscale [α‐SiW12O40]4− counterions, displaying uncommon optoelectronic responses. Besides, the fabricated synaptic device based on this material can achieve dual‐modulation of synaptic plasticity due to the synergetic effect of electron reservoir POM and photoinduced electron transfer. And it can successfully simulate learning and memory processes similar to those in biological systems. The result provides a facile and effective strategy to customize multi‐modality artificial synapses in the field of crystal engineering, which opens a new direction for developing high‐performance neuromorphic devices.
Standardized Figures of Merit for Proper Benchmarking of Photocatalytic Inactivation of Bacteria Using Thin Films Based on TiO2 Nanostructures
Authors: Romero‐Morán Alejandra , Molina‐Reyes Joel
Published: July 2023

The study of photocatalysts fixed to surfaces for the inactivation of bacteria in wastewater has increased in recent years. However, there are no standardized methods to analyze the photocatalytic antibacterial activity of these materials, and no systematic studies have attempted to relate this activity to the number of reactive oxygen species generated during UV‐light irradiation. Additionally, studies regarding photocatalytic antibacterial activity are usually carried out with varying pathogen concentrations, UV light doses, and catalyst amounts, making it difficult to compare results across different materials. The work introduces the photocatalytic bacteria inactivation efficiency (PBIE) and bacteria inactivation potential of hydroxyl radicals (BIPHR) figures of merit for evaluating the photocatalytic activity of catalysts fixed onto surfaces for bacteria inactivation. To demonstrate their applicability, these parameters are calculated for various photocatalytic TiO2‐based coatings, accounting for the catalyst area, the kinetic reaction rate constant associated with bacteria inactivation and hydroxyl radical formation, reactor volume, and UV light dose. This approach enables a comprehensive comparison of photocatalytic films prepared by different fabrication techniques and evaluated under diverse experimental conditions, with potential applications in the design of fixed‐bed reactors.
Heterologous protein production in filamentous fungi
Authors: Liu Dujuan , Garrigues Sandra , de Vries Ronald P.
Published: July 2023

Filamentous fungi are able to produce a wide range of valuable proteins and enzymes for many industrial applications. Recent advances in fungal genomics and experimental technologies are rapidly changing the approaches for the development and use of filamentous fungi as hosts for the production of both homologous and heterologous proteins. In this review, we highlight the benefits and challenges of using filamentous fungi for the production of heterologous proteins. We review various techniques commonly employed to improve the heterologous protein production in filamentous fungi, such as strong and inducible promoters, codon optimization, more efficient signal peptides for secretion, carrier proteins, engineering of glycosylation sites, regulation of the unfolded protein response and endoplasmic reticulum associated protein degradation, optimization of the intracellular transport process, regulation of unconventional protein secretion, and construction of protease-deficient strains.

Key points

• This review updates the knowledge on heterologous protein production in filamentous fungi.

• Several fungal cell factories and potential candidates are discussed.

• Insights into improving heterologous gene expression are given.
Rhizobacterial Isolates from Prosopis limensis Promote the Growth of Raphanus sativus L. Under Salt Stress
Authors: Flores Clavo Rene , Valladolid-Suyón Esteban , Reinoza-Farroñan Karin , Asmat Ortega Cristian , Riboldi Monteiro Pedro Henrique , Apaza-Castillo Gladys A. , Zuñiga-Valdera Gabriel , Fantinatti Garboggini Fabiana , Iglesias-Osores Sebastian , Carreño-Farfán Carmen Rosa
Published: July 2023

Microbial biotechnology employes techniques that rely based on the natural interactions that occur in ecosystems. Bacteria, including rhizobacteria, play an important role in plant growth, providing agricultural crops with an alternative that can mitigate the negative effects of abiotic stress, such as those caused by saline environments. In this study, bacterial isolates were obtained from soil and roots ofProsopis limensis Benthamfrom the department of Lambayeque, Peru. This region has high salinity levels, therefore, the collected samples were used to isolate plant growth-promoting rhizobacteria (PGPR), which were identified through morphological, and physical-biochemical characteristics. These salt tolerant bacteria were screened phosphate solubilization, indole acetic acid, deaminase activity and molecular characterization by 16S rDNA sequencing. Eighteen samples from saline soils of theProsopis limensisplants in the northern coastal desert of San Jose district, Lambayeque, Peru. The bacterial isolates were screened for salt tolerance ranging from 2 to 10%, a total of 78 isolates were found. Isolates 03, 13 and 31 showed maximum salt tolerance at 10%, in vitro ACC production, phosphate solubilization and IAA production. The three isolates were identified by sequencing the amplified 16S rRNA gene and were found to bePseudomonassp. 03 (MW604823),Pseudomonassp. 13 (MW604824) andBordetellasp. 31 (MW604826). These microorganisms promoted the germination of radish plants and increased the germination rates for treatments T2, T3 and T4 by 129, 124 and 118% respectively. The beneficial effects of salt tolerant PGPR isolates isolated from saline environments can be new species, used to overcome the detrimental effects of salt stress on plants. The biochemical response and inoculation of the three isolates prove the potential of using these strains as a source of products that can be employed for the development of new compounds proving their potential as biofertilizers for saline environments.
Initial therapeutic anticoagulation with rivaroxaban compared to prophylactic therapy with heparins in moderate to severe COVID-19: results of the COVID-PREVENT randomized controlled trial
Authors: Rauch-Kröhnert Ursula , Puccini Marianna , Placzek Marius , Beyer-Westendorf Jan , Jakobs Kai , Friebel Julian , Hein Selina , Seidel Mirko , Pieske Burkert , Massberg Steffen , Witzenrath Martin , Zeiher Andreas , Friede Tim , Anker Stefan D. , Landmesser Ulf
Published: July 2023

Background

COVID-19 is associated with a prothrombotic state. Current guidelines recommend prophylactic anticoagulation upon hospitalization.

Methods

COVID-PREVENT, an open-label, multicenter, randomized, clinical trial enrolled patients (≥ 18 years) with moderate to severe COVID-19 and age-adjusted d-dimers > 1.5 upper limit of normal (ULN). The participants were randomly assigned (1:1) to receive either therapeutic anticoagulation with rivaroxaban 20 mg once daily or thromboprophylaxis with a heparin (SOC) for at least 7 days followed by prophylactic anticoagulation with rivaroxaban 10 mg once daily for 28 days or no thromboprophylaxis. The primary efficacy outcome was the d-dimer level and the co-primary efficacy outcome the 7-category ordinal COVID-19 scale by WHO at 7 days post randomization. The secondary outcome was time to the composite event of either venous or arterial thromboembolism, new myocardial infarction, non-hemorrhagic stroke, all-cause death or progression to intubation and invasive ventilation up to 35 days post randomization.

Results

The primary efficacy outcome d-dimer at 7 days was not different between patients assigned to therapeutic (n = 55) or prophylactic anticoagulation (n = 56) (1.21 mg/L [0.79, 1.86] vs 1.27 mg/L [0.79, 2.04], p = 0.78). In the whole study population d-dimer was significantly lower at 7 days compared to baseline (1.05 mg/L [0.75, 1.48] vs 1.57 mg/L [1.13, 2.19], p < 0.0001). Therapy with rivaroxaban compared to SOC was not associated an improvement on the WHO 7-category ordinal scale at 7 days (p = 0.085). Rivaroxaban improved the clinical outcome measured by the score in patients with a higher baseline d-dimer  > 2.0 ULN (exploratory analysis; 0.632 [0.516, 0.748], p = 0.026). The secondary endpoint occurred in 6 patients (10.9%) in the rivaroxaban group and in 12 (21.4%) in the SOC group (time-to-first occurrence of the components of the secondary outcome: HR 0.5; 95% CI 0.15–1.67; p = 0.264). There was no difference in fatal or non-fatal major or clinically relevant non-major bleeding between the groups.

Conclusions

Therapeutic anticoagulation with rivaroxaban compared to prophylactic anticoagulation with a heparin did not improve surrogates of clinical outcome in patients with moderate to severe COVID-19. Whether initial rivaroxaban at therapeutic doses might be superior to thromboprophylaxis in patients with COVID-19 and a high risk as defined by d-dimer  > 2 ULN needs confirmation in further studies.

Graphical abstract
Surgical management of bifocal femoral fractures: a systematic review and pooled analysis of treatment with a single implant versus double implants
Authors: Cnossen J. D. , Van Lieshout Esther M. M. , Verhofstad Michael H. J.
Published: July 2023

Introduction

Fractures of the proximal femur accompanied by a fracture of the femoral shaft are relatively rare, with a reported prevalence between 1 and 12%. Multiple surgical options are available, consisting of treatment with a single implant or with double implants. Controversy exists about the optimal management. A systematic review and pooled analysis were performed to assess the most reliable treatment for bifocal femoral fractures of the femur.

Materials and methods

A literature search was conducted on July 15, 2022. Selected studies were screened on title and abstract by two researchers independently, and full texts were read by both authors. Emphasis was put on adverse events such as postoperative infection, healing complications, malalignment, and functional outcome using either a single implant or double implants.

Results

For the proximal femoral fractures, no significant difference could be confirmed for avascular necrosis of the femoral neck (5.1% for single implant and 3.8% for double implants), nonunion (6.4% for single implant and 7.8% for double implants), or varus malalignment (6.6% for single implant and 10.9% for double implants). This study also suggests that the number of implants is irrelevant for complications of the femoral shaft regarding the rates of postoperative infection and healing complications. Pooled rates of bone healing complications were 1.6–2.7-fold higher when patients were treated with a single implant, but statistical significance could not be confirmed. For hardware failure, revision surgery, leg length discrepancy, and functional outcome, no difference between the two groups was found either.

Conclusions

The pooled proportions of all postoperative complications had overlapping confidence intervals; thus, no inference about a statistically significant difference on the number of implants used for treating ipsilateral fractures of the femur can be made. Both treatment groups showed a similar functional outcome at the last moment of follow-up, with more than 75% of the patients reporting a good outcome.
Mechanisms of peripheral sensitization in endometriosis patients with peritoneal lesions and acyclical pain
Authors: Velho Renata Voltolini , Sehouli Jalid , Mechsner Sylvia
Published: July 2023

Purpose

Endometriosis (EM) is one of the most frequent differential diagnoses concerning chronic pelvic pain. Women under hormonal therapy (HT) often benefit from it but sometimes suffer a setback and develop acyclical pelvic pain. Due to the assumption that mechanisms of neurogenic inflammation are involved in the generation of chronic pelvic pain, we aimed to investigate the expression of sensory nerve markers in EM-associated nerve fibers of patients with/without HT.

Methods

Laparoscopically excised peritoneal samples from 45 EM and 10 control women were immunohistochemically stained for: PGP9.5, Substance P (SP), NK1R, NGFp75, TRPV-1, and TrkA. Demographics and severity of pain were documented.

Results

EM patients showed a higher nerve fiber density (PGP9.5 and SP) and increased expression of NGFp75, TRPV1, TrkA, and NK1R in blood vessels and immune cells compared with controls. Patients with HT have cycle-dependent pelvic pain but suffer from acyclical pelvic pain. Interestingly, reducing NK1R expression in blood vessels under HT was observed. A correlation between dyspareunia severity and nerve fibers density and between NGFRp75 expression in blood vessels and cycle-dependent pelvic pain severity was observed.

Conclusion

Patients under HT have no ovulation and no (menstrual) bleeding, which correlate with inflammation and cyclical pain. However, acyclical pain seems to be due to peripheral sensitization once it is present under treatment. Neurotransmitters, like SP and their receptors, are involved in mechanisms of neurogenic inflammation, which are relevant for pain initiation. These findings indicate that in both groups (EM with/without HT), neurogenic inflammation is present and responsible for acyclical pain.
Effectiveness of teriflunomide on No Evidence of Disease Activity and cognition in relapsing remitting multiple sclerosis: results of the NEDA3PLUS study
Authors: Amato Maria Pia , Bergamaschi Roberto , Centonze Diego , Mirabella Massimiliano , Marfia Girolama Alessandra , Totaro Rocco , Lus Giacomo , Brescia Morra Vincenzo , Aguglia Umberto , Comi Cristoforo , Cavalla Paola , Zaffaroni Mauro , Rovaris Marco , Grimaldi Luigi Maria , Leoni Stefania , Malucchi Simona , Baldi Eleonora , Romano Marcello , Falcini Mario , Perini Paola , Assetta Maurizio , Portaccio Emilio , Sommacal Sergio , Olivieri Nunzio , Parodi Franco , Todaro Daniele Santo , Grassivaro Nicoletta , Farina Alberto , Mondino Margaret Mary , Filippi Massimo , Trojano Maria
Published: July 2023

Background

Cognitive impairment (CI) is a prevalent and debilitating manifestation of multiple sclerosis (MS); however, it is not included in the widely used concept of No Evidence of Disease Activity (NEDA-3). We expanded the NEDA-3 concept to NEDA-3 + by encompassing CI assessed through the Symbol Digit Modality Test (SDMT) and evaluated the effect of teriflunomide on NEDA3 + in patients treated in a real-world setting. The value of NEDA-3 + in predicting disability progression was also assessed.

Methods

This 96-weeks observational study enrolled patients already on treatment with teriflunomide for ≥ 24 weeks. The predictiveness of NEDA-3 and NEDA-3 + at 48 weeks on the change in motor disability at 96 weeks was compared through a two-sided McNemar test.

Results

The full analysis set (n = 128; 38% treatment naïve) featured relatively low level of disability (baseline EDSS = 1.97 ± 1.33). NEDA-3 and NEDA-3 + statuses were achieved by 82.8% and 64.8% of patients, respectively at 48 weeks vs. baseline, and by 57.0% and 49.2% of patients, respectively at 96 weeks vs. baseline. All patients except one were free of disability progression at Week 96, and NEDA-3 and NEDA-3 + were equally predictive. Most patients were free of relapse (87.5%), disability progression (94.5%) and new MRI activity (67.2%) comparing 96 weeks with baseline. SDMT scores were stable in patients with baseline score ˃35 and improved significantly in those with baseline score ≤ 35. Treatment persistence was high (81.0% at Week 96).

Conclusion

Teriflunomide confirmed its real-world efficacy and was found to have a potentially beneficial effect on cognition.
Therapy delay due to COVID-19 pandemic among European women with breast cancer: prevalence and associated factors
Authors: Gremke Niklas , Griewing Sebastian , Bausch Elena , Alymova Svetlana , Wagner Uwe , Kostev Karel , Kalder Matthias
Published: July 2023

Purpose

This study investigates the impact of the COVID-19 pandemic on breast cancer (BC) care, analyzing treatment delays and factors associated with them.

Methods

This retrospective cross-sectional study analyzed data from the Oncology Dynamics (OD) database. Surveys of 26,933 women with BC performed between January 2021 and December 2022 in Germany, France, Italy, the United Kingdom, and Spain were examined. The study focused on determining the prevalence of treatment delays due to the COVID-19 pandemic, considering factors such as country, age group, treating facility, hormone receptor status, tumor stage, site of metastases, and Eastern Cooperative Oncology Group (ECOG) status. Baseline and clinical characteristics were compared for patients with and without therapy delay using chi-squared tests, and a multivariable logistic regression analysis was conducted to explore the association between demographic and clinical variables and therapy delay.

Results

The present study found that most therapy delays lasted less than 3 months (2.4%). Factors associated with higher risk of delay included being bedridden (OR 3.62; 95% CI 2.51–5.21), receiving neoadjuvant therapy (OR 1.79; 95% CI 1.43–2.24) compared to adjuvant therapy, being treated in Italy (OR 1.58; 95% CI 1.17–2.15) compared to Germany or treatment in general hospitals and non-academic cancer facilities (OR 1.66, 95% CI 1.13–2.44 and OR 1.54; 95% CI 1.14–2.09, respectively) compared to treatment by office-based physicians.

Conclusion

Addressing factors associated with therapy delays, such as patient performance status, treatment settings, and geographic location, can help guide strategies for improved BC care delivery in the future.
Barriers and facilitators to social prescribing in child and youth mental health: perspectives from the frontline
Authors: Hayes D. , Olsson A. , Begum S. , Bertotti M. , Jarvis-Beesley P. , Stapley E.
Published: July 2023

There is growing interest in the role of Social Prescribing (SP) to help promote mental well-being and support individuals with mental health difficulties. Yet, implementation of SP to children and young people (CYP) has proved slow and underdeveloped compared with adult populations. Understanding the barriers and facilitators will help key stakeholders to better embed SP for CYP into practice. Using the Theoretical Domains Framework (TDF), a comprehensive, theoretical-led framework, underpinned by 33 behaviour change theories and 128 constructs, perceived barriers and facilitators to SP were investigated. The sample comprised of 11 Link Workers and 9 individuals involved in facilitating SP with CYP, who took part in semi-structured interviews. Transcripts were analysed using a deductive thematic analysis, and themes were coded under each theoretical domain. Overall, 33 barriers and facilitators for SP were identified across 12 domains of the TDF. Under capability, barriers and facilitators were found for knowledge, skills, memory/attention/decision making processes, and behavioural regulation. For opportunity, barriers and facilitators were found for social/professional influences, as well as environmental context and resources. Finally, for motivation, domains covered included: beliefs about consequences, beliefs about capabilities, optimism, motivations/goals, reinforcement, and emotions. Findings suggest that a wide range of barriers and facilitators affect the implementation of CYP SP to improve mental health and well-being. Interventions which target different domains related to capability, opportunity and motivation should be developed to better facilitate CYP SP.
Fault displacement hazard estimation at lifeline–fault crossings: A simplified approach for engineering applications
Authors: Melissianos Vasileios E. , Danciu Laurentiu , Vamvatsikos Dimitrios , Basili Roberto
Published: July 2023

Lifelines, such as pipelines, roads, and tunnels, are critical infrastructure and when crossing active tectonic faults, a reliable estimation of the fault displacement in case of an earthquake is required. The first and simplest approach is to use empirical fault scaling relations to compute the design fault displacement, but this may result in an unknown level of safety. Thus, the probabilistic fault displacement hazard analysis (PFDHA) is the appropriate tool to assess the fault displacement hazard within a performance-based framework. Based upon an established PFDHA model, we present a simplified approach for engineering applications focusing on the lifeline–fault crossing along with appropriate simplifications and assumptions to extend its applicability to numerous faults. The aim is to provide a structure-independent approach of PFDHA that can be used when a site-specific study is not required, not possible (e.g., absence of recent sediments for dating past events), or too cumbersome, e.g., for lifeline route selection. Additionally, an in-depth investigation is presented on the key parameters, such as maximum earthquake magnitude, fault length, recurrence rate of all earthquakes above a minimum magnitude, and lifeline-fault crossing site, and how they affect the hazard level. This approach will be the basis for deriving hazard-consistent expressions to approximate fault displacement for use within the Eurocodes. The latter is intended to serve as a compromise between hazard-agnostic fault scaling relations and a comprehensive PFDHA, which requires detailed calculations and site-specific seismological data.
100 days of Adolescence: Elucidating Externalizing Behaviors Through the Daily Assessment of Inhibitory Control
Authors: Chaku Natasha , Yan Ran , Kelly Dominic P. , Zhang Zhuoran , Lopez-Duran Nestor , Weigard Alexander S. , Beltz Adriene M.
Published: July 2023

Inhibitory control is a transdiagnostic risk factor for externalizing behaviors, particularly during adolescence. Despite advances in understanding links between inhibitory control and externalizing behaviors across youth on average, significant questions remain about how these links play out in the day-to-day lives of individual adolescents. The goals of the current study were to: (1) validate a novel 100-occasion measure of inhibitory control; (2) assess links between day-to-day fluctuations in inhibitory control and individual differences in externalizing behaviors; and (3) illustrate the potential of intensive longitudinal studies for person-specific analyses of adolescent externalizing behaviors. Participants were 106 youth (57.5% female, Mage = 13.34 years; SDage = 1.92) who completed a virtual baseline session followed by 100 daily surveys, including an adapted Stroop Color Word task designed to assess inhibitory control. Results suggested that the novel task was generally reliable and valid, and that inhibitory control fluctuated across days in ways that were meaningfully associated with individual differences in baseline impulsive behaviors. Results of illustrative personalized analyses suggested that inhibitory control had more influence in the daily networks of adolescents who used substances during the 100 days than in a matched set of adolescents who did not. This work marks a path forward in intensive longitudinal research by validating a novel inhibitory control measure, revealing that daily fluctuations in inhibitory control may be a unique construct broadly relevant to adolescent externalizing problems, and at the same time, highlighting that links between daily inhibitory control and impulsive behaviors are adolescent-specific.
Symmetrical distributions of aminoacyl-tRNA synthetases during the evolution of the genetic code
Authors: José Marco V. , Bobadilla Juan R. , Zamudio Gabriel S. , de Farías Sávio Torres
Published: July 2023

In this work, we formulate the following question: How the distribution of aminoacyl-tRNA synthetases (aaRSs) went from an ancestral bidirectional gene (mirror symmetry) to the symmetrical distribution of aaRSs in a six-dimensional hypercube of the Standard Genetic Code (SGC)? We assume a primeval RNY code, two Extended Genetic RNA codes type 1 and 2, and the SGC. We outline the types of symmetries of the distribution of aaRSs in each code. The symmetry groups of aaRSs in each code are described, until the symmetries of the SGC display a mirror symmetry. Considering both Extended RNA codes the 20 aaRSs were already present before the Last Universal Ancestor. These findings reveal intricacies in the diversification of aaRSs accompanied by the evolution of the genetic code.
The tumor–stroma ratio and the immune microenvironment improve the prognostic prediction of pancreatic ductal adenocarcinoma
Authors: Lu Mei , Zou Yi , Fu Peiling , Li Yuyang , Wang Pengcheng , Li Guoping , Luo Sheng , Chen Yupeng , Guan Guoping , Zhang Sheng , Chen Linying
Published: July 2023

Tumor-infiltrating immune cells and fibroblasts are significant components of the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC), and they participate in tumor progression as closely as tumor cells. However, the relationship between the features of the TME and patient outcomes and the interactions among TME components are still unclear. In this study, we evaluated the PDAC TME in terms of the quantity and location of cluster of differentiation (CD)4+ T cells, CD8+ T cells, macrophages, stromal maturity, and tumor-stroma ratio (TSR), as evaluated by immunohistochemical staining of serial whole-tissue sections from 116 patients with PDAC. The density of T cells and macrophages (mainly activated macrophages) was significantly higher at the invasive margins (IMs) than at the tumor center (TC). CD4+ T cells were significantly association with all the other tumor-associated immune cells (TAIs) including CD8, CD68 and CD206 positive cells. Tumors of the non-mature (intermediate and immature) stroma type harbored significantly more CD8+ T cells at the IMs and more CD68+ macrophages at the IMs and the TC. The density of CD4+, CD8+, and CD206+ cells at the TC; CD206+ cells at the IMs; and tumor-node-metastasis (TNM) staging were independent risk factors for patient outcomes, and the c-index of the risk nomogram for predicting the survival probability based on the TME features and TNM staging was 0.772 (95% confidence interval: 0.713–0.832). PDAC harbored a significantly immunosuppressive TME, of which the IMs were the hot zones for TAIs, while cells at the TC were more predictive of prognosis. Our results indicated that the model based on the features of the TME and TNM staging could predict patient outcomes.