bluuebunny/crossref_metadata_2025 huggingface dataset:
The silver paste containing ZnO-B2O3-SiO2 glass sintered at high temperature with low solid content formed high performance conductive thick film on MgTiO3 microwave ceramics
Authors: Liu Yun Chuan , Zhang Li Ying , Yu Xiang Lei , Li Wei Chao , Li Jun Peng , Gan Guo You
Published: April 2023

A high-temperature conductive silver slurry containing lead-free ZnO-B2O3-SiO2 glass for metallization of ceramic MgTiO3 substrate has been prepared. The ZnO-B2O3-SiO2 glass was obtained by high-temperature melting and cold extraction with a transition temperature (Tg) of 579 °C and thermal stability (∆T) of 105 °C as an inorganic bonding phase of high-temperature conductive silver paste. Then, silver paste with different glass powder content was sintered on ceramic MgTiO3 substrate between 730 °C and 930 °C in increments of 50 °C. Characterization of the prepared materials revealed that their resistivity increases with the increase in glass powder content and decreases with the increase in sintering temperature. Sintering temperature and glass content have significant effects on the resistivity and adhesion of the thick silver film. When the silver paste with a glass content of 1.1 wt% was sintered at 830 °C for 10 min, the resulting thick silver film had a low resistivity of 1.81 μΩ·cm (1.65 μΩ·cm for silver) and a good adhesive strength of 39.4 N mm−2. During the sintering process, the glass material melts and wets the silver powder, which promotes the sintering of the silver powder to form a dense network structure and improves the electrical conductivity of the silver film. In addition, the formation of ZnTiO3 by chemical reactions between the glass and the substrate was observed, which dramatically improved the bonding strength of the silver film. Therefore, lead-free silver paste containing ZnO-B2O3-SiO2 glass powder and MgTiO3 ceramics has broad development prospects in ceramic filters.
A new purification method for 2-mercaptobenzothiazole and its application as vulcanization accelerator
Authors: Shen Yuhong , Jing Xianhong , Mu Xueliang , Dou Jinpeng , Zhang Qingwei , Zhang Yidong , Liu Yanjun , Li Zhenqiu
Published: April 2023

In this work, a new purification method for 2-Mercaptobenzothiazole (MBT) and its application as a vulcanization accelerator was reported, and the properties of MBT samples were comprehensively investigated. According to the chemical equation of this purified reaction, the byproduct of the CO2 method was easy to treat. Results showed that the melting point and yield of experimental CAMBT samples were increased to 173.6 °C and 93.11%, respectively. The chemical structure and crystal absorption peak of all MBT samples were also measured by the FTIR and XRD analysis. Thermogravimetric analysis was used to study the residue of resin in MBT samples. Element content confirmed the existence of C, N, H, and S elements, and there were no other elements in the products. What is more important, the mechanical properties of experimental CDMBT@NR and SAMBT@NR samples were better than that of UMBT@NR. Thus, this paper offers a new purification method for MBT and investigates its application as a vulcanization accelerator.
Recent developments in the preparation and assembly of two-dimensional plate materials in Langmuir–Blodgett films: a review
Authors: Zhao Tianyue , Wang Ran , Li Lin , Jiao Tifeng
Published: April 2023

In recent years, two-dimensional (2D) plate materials have become the most attractive class of candidate materials for a wide range of potential applications due to their unique structural characteristics and physicochemical properties. Starting from graphene, 2D plate materials have become a large family with many members and diverse categories. Especially in recent years, we have made some significant breakthroughs in the field of 2D materials. Langmuir–Blodgett (LB) technology is an advanced technology for preparing ultrathin films with highly ordered molecules by using its unique dynamic interface in the preparation process, which can effectively control and adjust the film material with layered nanostructures. With the advancement of LB technology, different thin film materials need to be prepared to realize various functions. This paper summarizes the research progress and future perspectives of LB technology based on 2D materials.
Data-driven prediction of the performance of enhanced surfaces from an extensive CFD-generated parametric search space
Authors: Larrañaga A , Brunton S L , Martínez J , Chapela S , Porteiro J
Published: April 2023

Machine learning has rapidly been adopted in virtually all areas of engineering in recent years. This paper develops a machine learning model capable of predicting the performance of parametrically generated enhanced microsurface geometries for cooling electronic and power systems. Designing this type of geometry usually involves expensive computational fluid dynamics (CFD) simulations, limiting the number of candidate geometries that may be tested. For this reason, when searching for new geometries for a given application, designs are usually restricted to a simplified subset of basic shapes to reduce the complexity and dimension of the search space. In an effort to add geometrical diversity and explore singular morphologies, we have developed an algorithm capable of characterizing almost any geometry, based on an extensive CFD database with more than 15 800 geometries obtained from a Monte Carlo sampling of the space of possible geometries. With this framework, it is possible to estimate various quantities of interest, such as the heat flux in the enhanced zone and total drag, with relative errors below 10% and 2%, respectively. Thus, we establish the utility of machine learning to develop surrogate models for the rapid performance prediction of novel enhanced microsurfaces.
Expert perspectives for the pharmacist on facilitating and improving the use of albumin in cirrhosis
Authors: Kugelmas Marcelo , Loftus Michelle , Owen Emily J , Wadei Hani , Saab Sammy
Published: April 2023

Purpose

Albumin, the most abundant and arguably most important protein in the human body, plays a unique role in decompensated cirrhosis because its structure and function are quantitatively and qualitatively affected. A literature review was performed to provide insights into albumin use. The manuscript was developed using a multidisciplinary approach; 2 hepatologists, a nephrologist, a hospitalist, and a pharmacist, who are all members of or work closely with the Chronic Liver Disease Foundation, collaborated to write this expert perspective review.

Cirrhosis represents the potential end in the spectrum of all chronic liver diseases. Decompensated cirrhosis, defined by the overt manifestation of liver failure (eg, ascites, hepatic encephalopathy, variceal bleeding), is the inflection point associated with increased mortality. Human serum albumin (HSA) infusion serves an important role in the treatment of advanced liver disease. The benefits of HSA administration in patients with cirrhosis are widely accepted, and its use has been advocated by several professional societies. However, inappropriate HSA use can lead to significant adverse patient events. This paper discusses the rationale for the administration of HSA in the treatment of complications of cirrhosis, analyzes the data on the use of HSA in cirrhosis, and streamlines practical recommendations set forth in published guidance.

Conclusion

Use of HSA in clinical practice needs to be improved. The objective of this paper is to empower pharmacists to facilitate and improve the use of HSA in patients with cirrhosis at their practice sites.
Bipolar Radiofrequency-Assisted Liposuction for Cervical Contouring in Eastern Asians
Authors: Yen ShihChun , Wang JiGeng , Gao Xiang , Zhu QiuXuan , Song CaiYing , Zhu Fei
Published: April 2023

Background

East Asian beauty standards uphold a V-shaped face and a long slender neck. Some patients are dissatisfied with the concurrent nonsurgical treatment and prefer limited downtime with minimally invasive procedures to achieve a natural skin-tightening outcome. The authors performed bipolar radiofrequency-assisted liposuction (RFAL) to achieve cervical rejuvenation.

Objectives

To evaluate the efficacy and safety of RFAL for the treatment of cervical skin and soft-tissue laxity in Eastern Asians.

Methods

In total, 66 patients with neck skin and soft-tissue laxity were treated with bipolar RFAL under tumescent local anesthesia. Further, the surgical outcomes were evaluated based on patient satisfaction score and the Global Aesthetic Improvement Scale (GAIS) score at 6 months postoperatively. Moreover, the incidence of postoperative complications was determined.

Results

All patients were followed up for at least 6 months. After RFAL technologies treatment, significant improvement in the neck contour was observed. The average GAIS score was 3.03 (4, very much improved; 3, much improved; 2, improved; 1, no change; and 0, worsened). Approximately 93% of patients were satisfied with the RFAL neck contouring outcome. Notably, no serious complications requiring further intervention were encountered in this series.

Conclusions

The described RFAL treatment significantly improved the refinement of neck contouring in Eastern Asian subjects. The simple, minimally invasive cervical procedure under local anesthesia improve the cervical-mental angle definition, tissue-tightening effect, face slimming, and the mandibular line. No serious adverse events except mild complications were reported. This treatment could achieve extraordinary results with a high safety profile.

Level of Evidence: 4
AGAT-PPIS: a novel protein–protein interaction site predictor based on augmented graph attention network with initial residual and identity mapping
Authors: Zhou Yuting , Jiang Yongquan , Yang Yan
Published: April 2023

Identifying protein–protein interaction (PPI) site is an important step in understanding biological activity, apprehending pathological mechanism and designing novel drugs. Developing reliable computational methods for predicting PPI site as screening tools contributes to reduce lots of time and expensive costs for conventional experiments, but how to improve the accuracy is still challenging. We propose a PPI site predictor, called Augmented Graph Attention Network Protein-Protein Interacting Site (AGAT-PPIS), based on AGAT with initial residual and identity mapping, in which eight AGAT layers are connected to mine node embedding representation deeply. AGAT is our augmented version of graph attention network, with added edge features. Besides, extra node features and edge features are introduced to provide more structural information and increase the translation and rotation invariance of the model. On the benchmark test set, AGAT-PPIS significantly surpasses the state-of-the-art method by 8% in Accuracy, 17.1% in Precision, 11.8% in F1-score, 15.1% in Matthews Correlation Coefficient (MCC), 8.1% in Area Under the Receiver Operating Characteristic curve (AUROC), 14.5% in Area Under the Precision-Recall curve (AUPRC), respectively.
ChemGAPP: a tool for chemical genomics analysis and phenotypic profiling
Authors: Doherty Hannah M , Kritikos George , Galardini Marco , Banzhaf Manuel , Moradigaravand Danesh
Published: April 2023

Motivation

High-throughput chemical genomic screens produce informative datasets, providing valuable insights into unknown gene function on a genome-wide level. However, there is currently no comprehensive analytic package publicly available. We developed ChemGAPP to bridge this gap. ChemGAPP integrates various steps in a streamlined and user-friendly format, including rigorous quality control measures to curate screening data.

Results

ChemGAPP provides three sub-packages for different chemical-genomic screens: ChemGAPP Big for large-scale screens; ChemGAPP Small for small-scale screens; and ChemGAPP GI for genetic interaction screens. ChemGAPP Big, tested against the Escherichiacoli KEIO collection, revealed reliable fitness scores which displayed biologically relevant phenotypes. ChemGAPP Small demonstrated significant changes in phenotype in a small-scale screen. ChemGAPP GI was benchmarked against three sets of genes with known epistasis types and successfully reproduced each interaction type.

Availability and implementation

ChemGAPP is available at https://github.com/HannahMDoherty/ChemGAPP, as a standalone Python package as well as Streamlit applications.
A sensory neuron-specific long non-coding RNA reduces neuropathic pain by rescuing KCNN1 expression
Authors: Wang Bing , Ma Longfei , Guo Xinying , Du Shibin , Feng Xiaozhou , Liang Yingping , Govindarajalu Gokulapriya , Wu Shaogen , Liu Tong , Li Hong , Patel Shivam , Bekker Alex , Hu Huijuan , Tao Yuan-Xiang
Published: April 2023

Nerve injury to peripheral somatosensory system causes refractory neuropathic pain. Maladaptive changes of gene expression in primary sensory neurons are considered molecular basis of this disorder. Long non-coding RNAs (lncRNAs) are key regulators of gene transcription; however, their significance in neuropathic pain remains largely elusive.Here, we reported a novel lncRNA, named sensory neuron-specific lncRNA (SS-lncRNA), for its expression exclusively in dorsal root ganglion (DRG) and trigeminal ganglion. SS-lncRNA was predominantly expressed in small DRG neurons and significantly downregulated due to a reduction of early B cell transcription factor 1 in injured DRG after nerve injury. Rescuing this downregulation reversed a decrease of the calcium-activated potassium channel subfamily N member 1 (KCNN1) in injured DRG and alleviated nerve injury-induced nociceptive hypersensitivity. Conversely, DRG downregulation of SS-lncRNA reduced the expression of KCNN1, decreased total potassium currents and afterhyperpolarization currents and increased excitability in DRG neurons and produced neuropathic pain symptoms.Mechanistically, downregulated SS-lncRNA resulted in the reductions of its binding to Kcnn1 promoter and heterogeneous nuclear ribonucleoprotein M (hnRNPM), consequent recruitment of less hnRNPM to the Kcnn1 promoter and silence of Kcnn1 gene transcription in injured DRG.These findings indicate that SS-lncRNA may relieve neuropathic pain through hnRNPM-mediated KCNN1 rescue in injured DRG and offer a novel therapeutic strategy specific for this disorder.
Establishing a natural history of X-linked dystonia parkinsonism
Authors: Acuna Patrick , Supnet-Wells Melanie Leigh , Spencer Neil A , de Guzman Jan Kristoper , Russo Massimiliano , Hunt Ann , Stephen Christopher , Go Criscely , Carr Samuel , Ganza Niecy Grace , Lagarde John Benedict , Begalan Shin , Multhaupt-Buell Trisha , Aldykiewicz Gabrielle , Paul Lisa , Ozelius Laurie , Bragg D Cristopher , Perry Bridget , Green Jordan R , Miller Jeffrey W , Sharma Nutan
Published: April 2023

X-linked dystonia parkinsonism is a neurodegenerative movement disorder that affects men whose mothers originate from the island of Panay, Philippines. Current evidence indicates that the most likely cause is an expansion in the TAF1 gene that may be amenable to treatment. To prepare for clinical trials of therapeutic candidates for X-linked dystonia parkinsonism, we focused on the identification of quantitative phenotypic measures that are most strongly associated with disease progression. Our main objective is to establish a comprehensive, quantitative assessment of movement dysfunction and bulbar motor impairments that are sensitive and specific to disease progression in persons with X-linked dystonia parkinsonism. These measures will set the stage for future treatment trials. We enrolled patients with X-linked dystonia parkinsonism and performed a comprehensive oromotor, speech and neurological assessment. Measurements included patient-reported questionnaires regarding daily living activities and both neurologist-rated movement scales and objective quantitative measures of bulbar function and nutritional status. Patients were followed for 18 months from the date of enrollment and evaluated every 6 months during that period. We analysed a total of 87 men: 29 were gene-positive and had symptoms at enrollment, seven were gene-positive and had no symptoms at enrollment and 51 were gene-negative. We identified measures that displayed a significant change over the study. We used principal variables analysis to identify a minimal battery of 21 measures that explains 67.3% of the variance over the course of the study. These measures included patient-reported, clinician-rated and objective quantitative outcomes that may serve as endpoints in future clinical trials.
Nogo receptor-Fc delivered by haematopoietic cells enhances neurorepair in a multiple sclerosis model
Authors: Ye Sining , Theotokis Paschalis , Lee Jae Young , Kim Min Joung , Nheu Danica , Ellen Olivia , Bedford Thomas , Ramanujam Padmanabhan , Wright David K , McDonald Stuart J , Alrehaili Amani , Bakhuraysah Maha , Kang Jung Hee , Siatskas Christopher , Tremblay Cedric S , Curtis David J , Grigoriadis Nikolaos , Monif Mastura , Strittmatter Stephen M , Petratos Steven
Published: April 2023

Nogo receptor 1 is the high affinity receptor for the potent myelin-associated inhibitory factors that make up part of the inflammatory extracellular milieu during experimental autoimmune encephalomyelitis. Signalling through the Nogo receptor 1 complex has been shown to be associated with axonal degeneration in an animal model of multiple sclerosis, and neuronal deletion of this receptor homologue, in a disease specific manner, is associated with preserving axons even in the context of neuroinflammation. The local delivery of Nogo receptor(1-310)-Fc, a therapeutic fusion protein, has been successfully applied as a treatment in animal models of spinal cord injury and glaucoma. As multiple sclerosis and experimental autoimmune encephalomyelitis exhibit large numbers of inflammatory cell infiltrates within the CNS lesions, we utilized transplantable haematopoietic stem cells as a cellular delivery method of the Nogo receptor(1-310)-Fc fusion protein. We identified CNS-infiltrating macrophages as the predominant immune-positive cell type that overexpressed myc-tagged Nogo receptor(1-310)-Fc fusion protein at the peak stage of experimental autoimmune encephalomyelitis. These differentiated phagocytes were predominant during the extensive demyelination and axonal damage, which are associated with the engulfment of the protein complex of Nogo receptor(1-310)-Fc binding to myelin ligands. Importantly, mice transplanted with haematopoietic stem cells transduced with the lentiviral vector carrying Nogo receptor(1-310)-Fc and recovered from the peak of neurological decline during experimental autoimmune encephalomyelitis, exhibiting axonal regeneration and eventual remyelination in the white matter tracts. There were no immunomodulatory effects of the transplanted, genetically modified haematopoietic stem cells on immune cell lineages of recipient female mice induced with experimental autoimmune encephalomyelitis. We propose that cellular delivery of Nogo receptor(1-310)-Fc fusion protein through genetically modified haematopoietic stem cells can modulate multifocal experimental autoimmune encephalomyelitis lesions and potentiate neurological recovery.
Multi-omic integration via similarity network fusion to detect molecular subtypes of ageing
Authors: Yang Mu , Matan-Lithwick Stuart , Wang Yanling , De Jager Philip L , Bennett David A , Felsky Daniel
Published: April 2023

Molecular subtyping of brain tissue provides insights into the heterogeneity of common neurodegenerative conditions, such as Alzheimer’s disease. However, existing subtyping studies have mostly focused on single data modalities and only those individuals with severe cognitive impairment. To address these gaps, we applied similarity network fusion, a method capable of integrating multiple high-dimensional multi-omic data modalities simultaneously, to an elderly sample spanning the full spectrum of cognitive ageing trajectories. We analyzed human frontal cortex brain samples characterized by five omic modalities: bulk RNA sequencing (18 629 genes), DNA methylation (53 932 CpG sites), histone acetylation (26 384 peaks), proteomics (7737 proteins) and metabolomics (654 metabolites). Similarity network fusion followed by spectral clustering was used for subtype detection, and subtype numbers were determined by Eigen-gap and rotation cost statistics. Normalized mutual information determined the relative contribution of each modality to the fused network. Subtypes were characterized by associations with 13 age-related neuropathologies and cognitive decline. Fusion of all five data modalities (n = 111) yielded two subtypes (nS1 = 53, nS2 = 58), which were nominally associated with diffuse amyloid plaques; however, this effect was not significant after correction for multiple testing. Histone acetylation (normalized mutual information = 0.38), DNA methylation (normalized mutual information = 0.18) and RNA abundance (normalized mutual information = 0.15) contributed most strongly to this network. Secondary analysis integrating only these three modalities in a larger subsample (n = 513) indicated support for both three- and five-subtype solutions, which had significant overlap, but showed varying degrees of internal stability and external validity. One subtype showed marked cognitive decline, which remained significant even after correcting for tests across both three- and five-subtype solutions (pBonf = 5.9 × 10−3). Comparison to single-modality subtypes demonstrated that the three-modal subtypes were able to uniquely capture cognitive variability. Comprehensive sensitivity analyses explored influences of sample size and cluster number parameters. We identified highly integrative molecular subtypes of ageing derived from multiple high dimensional, multi-omic data modalities simultaneously. Fusing RNA abundance, DNA methylation, and histone acetylation measures generated subtypes that were associated with cognitive decline. This work highlights the potential value and challenges of multi-omic integration in unsupervised subtyping of post-mortem brain.
Blistering rash in a child
Authors: Mounsey Stephen J , Oluwole Ebunoluwa , Semkova Kristina , Abdelrahman Wedad
Published: April 2023

A 5-year-old child was brought to the dermatology department with a blistering rash on the lower limbs. Indirect and direct immunofluorescence, in conjunction with haematoxylin and eosin showed a rare blistering disorder.
Fibroscan–Aspartate Aminotransferase Score Predicts Liver-Related Outcomes, but Not Extrahepatic Events, in a Multicenter Cohort of People With Human Immunodeficiency Virus
Authors: Sebastiani Giada , Milic Jovana , Kablawi Dana , Gioè Claudia , Al Hinai Al Shaima , Lebouché Bertrand , Tsochatzis Emmanuel , Finkel Jemima , Ballesteros Luz Ramos , Ramanakumar Agnihotram V , Bhagani Sanjay , Benmassaoud Amine , Mazzola Giovanni , Cascio Antonio , Guaraldi Giovanni
Published: April 2023

Background

Nonalcoholic fatty liver disease (NAFLD) is frequent in people with human immunodeficiency virus (PWH). The Fibroscan–aspartate aminotransferase (FAST) score was developed to identify patients with nonalcoholic steatohepatitis (NASH) and significant fibrosis. We investigated prevalence of NASH with fibrosis and the value of FAST score in predicting clinical outcomes in PWH.

Methods

Transient elastography (Fibroscan) was performed in PWH without viral hepatitis coinfection from 4 prospective cohorts. We used FAST >0.35 to diagnose NASH with fibrosis. Incidence and predictors of liver-related outcomes (hepatic decompensation, hepatocellular carcinoma) and extrahepatic events (cancer, cardiovascular disease) were evaluated through survival analysis.

Results

Of the 1472 PWH included, 8% had FAST >0.35. Higher body mass index (adjusted odds ratio [aOR], 1.21 [95% confidence interval {CI}, 1.14–1.29]), hypertension (aOR, 2.24 [95% CI, 1.16–4.34]), longer time since HIV diagnosis (aOR, 1.82 [95% CI, 1.20–2.76]), and detectable HIV RNA (aOR, 2.22 [95% CI, 1.02–4.85]) were associated with FAST >0.35. A total of 882 patients were followed for a median of 3.8 years (interquartile range, 2.5–4.2 years). Overall, 2.9% and 11.1% developed liver-related and extrahepatic outcomes, respectively. Incidence of liver-related outcomes was higher in patients with FAST >0.35 versus FAST ≤0.35 (45.1 [95% CI, 26.2–77.7] vs 5.0 [95% CI, 2.9–8.6] per 1000 person-years). FAST >0.35 remained an independent predictor of liver-related outcomes (adjusted hazard ratio, 4.97 [95% CI, 1.97–12.51]). Conversely, FAST did not predict extrahepatic events.

Conclusions

A significant proportion of PWH may have NASH with significant liver fibrosis. FAST score predicts liver-related outcomes and can help management of this high-risk population.
Stratification of lymph node metastasis improves diagnostic efficiency in thoracic esophageal squamous cell carcinoma
Authors: Li Zhenxuan , Li Yin , Liu Xianben , Zheng Yan , Sun Haibo , Liang Guanghui , Wang Zongfei , Xing Wenqun
Published: April 2023

Introduction

Difference of the short diameter of lymph nodes in the main regions of esophageal squamous cell carcinoma (ESCC) and its value in the diagnosis of lymph nodes need to explore.

Methods

The clinical data of patients with thoracic ESCC who underwent surgical treatment in our hospital were collected. The short diameters of the largest lymph node in each region of the patient were measured by preoperative enhanced computed tomography (CT) and were compared with the postoperative pathology.

Results

A total of 477 patients with thoracic ESCC who did not receive neoadjuvant therapy were enrolled in this study. The receiver operating characteristic curve suggested that the short diameters of the paracardial nodes, the left gastric nodes, the right recurrent laryngeal nerve nodes, and the left recurrent laryngeal nerve nodes could well predict the postoperative pathology of the lymph nodes, with area under curve (AUC) of 0.958, 0.937, 0.931, and 0.915, the corresponding cut-off values of 5.7 mm, 5.7 mm, 5.5 mm, and 4.8 mm, the corresponding sensitivities of 94.7%, 85.4%, 88.7%, and 79.4%, and the corresponding specificities of 93.7%, 96.3%, 86.2%, and 95.0%, respectively. The AUC of the thoracic paraesophageal lymph nodes, the subcarinal nodes and all regional lymph nodes were 0.845, 0.688, and 0.776, respectively.

Conclusion

Region-based criterion for lymph node metastasis of thoracic ESCC is beneficial to improve the diagnostic efficiency of preoperative CT.
Using information criteria to select averages in CCE
Authors: Margaritella Luca , Westerlund Joakim
Published: April 2023

In the interactive effects panel data literature information criteria are commonly used to consistently determine which of the estimated principal components factors to include. The present paper shows that the same approach can be applied to factors estimated by taking the cross-sectional averages of the observables, as prescribed by the popular common correlated effects (CCE) approach. This should be useful to practitioners because at the moment there is no other theory that justifies the use of information criteria in CCE.
Leap or lag: left atrial appendage closure and guidelines
Authors: Camm A John
Published: April 2023

Atrial fibrillation (AF) is associated with life-threatening thromboembolism. Most emboli stem from thrombosis in the left atrial appendage (LAA). The current treatment of choice is oral anticoagulants (OACs), but a small proportion of patients cannot take OACs predominantly because of the so-called unacceptable bleeding risks. However, many who initially accept OACs subsequently stop therapy or reduce the OAC treatment to a potentially non-effective dose leaving them exposed to thromboembolic risk.

A relatively simple alternative therapy involves the catheter-based insertion of a LAA closure (LAAC) device to prevent thromboembolism from the LAA. There is a considerable evidence base for this therapy consisting of clinical trials and observational data which suggests comparable therapeutic efficacy with a possible small excess of ischaemic strokes.

Although LAAC has been very closely examined by regulators and approved for market release, guidelines from most professional societies give only weak recommendations for use of this device which may be the only known effective therapy available to some at-risk AF patients. Guidance materials from the same societies more enthusiastically endorse LAAC.

Clinical practice is running well ahead of the guidelines because equipoise has been lost by physicians faced with patients for whom they have no other effective therapy. Guideline writers are correct in providing recommendations which are less strong for LAAC than for OACs, for those who are able and willing to take OAC treatment, but for those who are not, a stronger recommendation is needed. But, should the guidelines lag behind or leap ahead of the available evidence?
In atrial fibrillation epilepsy risk differs between oral anticoagulants: active comparator, nested case-control study
Authors: Platzbecker Katharina , Müller-Fielitz Helge , Foraita Ronja , Koepp Matthias J , Voss Annemarie , Pflock René , Linder Roland , Pigeot Iris , Schink Tania , Schwaninger Markus
Published: April 2023

Aims

Atrial fibrillation (AF) is a risk factor for brain infarction, which can lead to epilepsy. We aimed to investigate whether treatment of AF with direct oral anticoagulants (DOACs) affects the risk of epilepsy in comparison to treatment with the vitamin K antagonist phenprocoumon (PPC).

Methods and results

We performed an active comparator, nested case-control study based on the German Pharmacoepidemiological Research Database that includes claims data from statutory health insurance providers of about 25 million persons since 2004. In 2011–17, 227 707 AF patients initiated treatment with a DOAC or PPC, of which 1828 cases developed epilepsy on current treatment with an oral anticoagulant. They were matched to 19 084 controls without epilepsy. Patients with DOAC treatment for AF had an overall higher risk of epilepsy with an odds ratio of 1.39, 95% CI (1.24; 1.55) compared to current PPC treatment. Cases had higher baseline CHA2DS2-VASc scores and more frequently a history of stroke than controls. After excluding patients with ischaemic stroke prior to the diagnosis of epilepsy, the risk of epilepsy was still higher on DOACs than on PPC. In contrast, within a cohort of patients with venous thromboembolism, the risk of epilepsy on treatment with DOACs was less elevated [adjusted odds ratio 1.15, 95% CI (0.98; 1.34)].

Conclusion

In patients with AF initiating oral anticoagulation, treatment with a DOAC was associated with an increased risk of epilepsy compared to the vitamin K antagonist PPC. Covert brain infarction may explain the observed elevated risk of epilepsy.
Association between anaemia and vitamin D insufficiency among 6- to 12-month-old infants: implications for clinical practice
Authors: Boonrusmee Sasivara , Kasemsripitak Staporn , Navykarn Thitiporn , Jaruratanasirikul Somchit
Published: April 2023

Background

Anaemia and vitamin D insufficiency (VDI) are among the most common nutritional problems. Anaemia screening is routinely performed; however, screening for VDI is not usually recommended.

Objectives

To study the association between anaemia and VDI and identify the risk factors for VDI.

Methods

We conducted a cross-sectional study of 120 infants aged 6–12 months attending a well-child clinic at Songklanagarind Hospital between December 2020 and November 2021. Sociodemographic data and 24-h food records were also collected. Blood samples were obtained for complete blood count and 25-hydroxyvitamin D [25(OH)D] levels. Logistic regression analysis was used to determine risk factors for VDI.

Results

The mean 25(OH)D level was 22.2 ± 8.9 ng/mL in anaemic infants and 27.2 ± 9.6 ng/mL in non-anaemic infants (P value 0.01). The median (IQR) Hb level was 11.1 g/dL (10.3, 11.4) in the VDI group and 11.4 g/dL (11, 12.1) in the non-VDI group (P value 0.002). The proportion of breastfed infants was higher in infants with anaemia (80%) (P < 0.001) and VDI (85.3%) (P < 0.001). Sunlight exposure <15 min/day (odds ratio [OR] 3.84; 95% confidence interval [CI]: 1.23–12.00; P = 0.020) was a risk factor, and vitamin D intake (OR 0.37; 95% CI: 0.20–0.74; P = 0.004) was a protective factor for VDI.

Conclusion

Infants with anaemia, short duration of sunlight exposure, breastfeeding, low vitamin D intake, and low iron intake were more likely to be vitamin D insufficient. However, after adjustment in the multivariate analyses, only sunlight exposure and vitamin D intake were significantly associated with vitamin D insufficiency.
Recruiting general practitioners and older patients with multimorbidity to randomized trials
Authors: McCarthy Caroline , Pericin Ivana , Smith Susan M , Moriarty Frank , Clyne Barbara
Published: April 2023

Background

Older patients with multimorbidity are under-represented in experimental research.

Objective

To explore the barriers and facilitators to general practitioner (GP) and older patient recruitment and retention in a cluster randomized controlled trial (RCT).

Method

This descriptive study uses qualitative and quantitative data from a cluster RCT, designed to evaluate the effectiveness of a medicines optimization intervention. The SPPiRE cluster RCT enrolled 51 general practices and 404 patients aged ≥65 years and prescribed ≥15 medicines. Quantitative data were collected from all recruited practices and 32 additional practices who were enrolled, but unable to recruit sufficient participants. Qualitative data were collected from purposive samples of intervention GPs (18/26), patients (27/208), and researcher logs and analysed thematically using inductive coding.

Results

Enrolment rates for practices and patients were 37% and 25%, respectively. Barriers to GP recruitment were lack of resources and to patient recruitment were difficulty understanding trial material and concern about medicines being taken away. GPs’ primary motivation was perceived importance of the research question, whereas patients’ primary motivation was trust in their GP. All general practices were retained. Thirty-five patients (8.6%) were lost to follow-up for primary outcomes, mainly because they had died and 45% did not return patient-reported outcome measures (PROMs).

Conclusion

Patient retention for the primary outcome was high, as it was collected directly from patient records. Patient completion of PROM data was poor, reflecting difficulty in understanding trial material. Recruiting older patients with multimorbidity to clinical trials is possible but requires significant resource and planning.

Trial registration

ISRCTN Registry ISRCTN12752680.
Regulatory Divergence as a Mechanism for X-Autosome Incompatibilities in Caenorhabditis Nematodes
Authors: Viswanath Athmaja , Cutter Asher D
Published: April 2023

The world's astounding biodiversity results from speciation, the process of formation of distinct species. Hybrids between species often have reduced fitness due to negative epistatic interactions between divergent genetic factors, as each lineage accumulated substitutions independently in their evolutionary history. Such negative genetic interactions can manifest as gene misexpression due to divergence in gene regulatory controls from mutations in cis-regulatory elements and trans-acting factors. Gene misexpression due to differences in regulatory controls can ultimately contribute to incompatibility within hybrids through developmental defects such as sterility and inviability. We sought to quantify the contributions of regulatory divergence to postzygotic reproductive isolation using sterile interspecies hybrids of two Caenorhabditis nematodes: Caenorhabditis briggsae and Caenorhabditis nigoni. We analyzed previous transcriptome profiles for two introgression lines with distinct homozygous X-linked fragments from C. briggsae in a C. nigoni genomic background that confers male sterility, owing to defects in spermatogenesis (Li R, et al. 2016. Specific down-regulation of spermatogenesis genes targeted by 22G RNAs in hybrid sterile males associated with an X-chromosome introgression. Genome Res. 26:1219–1232). Our analysis identified hundreds of genes that show distinct classes of nonadditive expression inheritance and regulatory divergence. We find that these nonoverlapping introgressions affect many of the same genes in the same way and demonstrate that the preponderance of transgressive gene expression is due to regulatory divergence involving compensatory and joint effects of cis- and trans-acting factors. The similar transcriptomic responses to nonoverlapping genetic perturbations of the X-chromosome implicate multiway incompatibilities as an important feature contributing to hybrid male sterility in this system.
Validity, Reliability, Responsiveness, and Feasibility of the Life-Space Assessment Administered via Telephone in Community-Dwelling Older Adults
Authors: Ullrich Phoebe , Hummel Merit , Hauer Klaus , Bauer Jürgen M , Werner Christian
Published: April 2023

Background and Objectives

The life-space assessment (LSA) is the most commonly used questionnaire to assess life-space mobility (LSM) in older adults, with well-established psychometric properties for face-to-face (FF) administration. However, these properties have not yet been explicitly studied when the LSA is administered by telephone. The aim of this study was to evaluate the concurrent and construct validity, test–retest reliability, responsiveness, and feasibility of a telephone-based LSA version (TE-LSA) in older adults.

Research Design and Methods

Fifty community-dwelling older adults (age = 79.3 ± 5.3 years) participated in the study. Concurrent validity was assessed against the FF-LSA construct validity by testing 15 a priori hypotheses on expected associations with LSM determinants, test–retest reliability via 2 telephone surveys 1 week apart, responsiveness after 8.5 ± 1.8 months in participants with improved, stable, and worsened mobility defined by 2 external criteria, and feasibility by the completion rate/time and ceiling/floor effects.

Results

Good to excellent agreement between the 2 different administration methods was found (intraclass correlation coefficient [ICC2,1] = 0.73–0.98). Twelve of 15 (80%) hypotheses on construct validity were confirmed. ICCs for test–retest reliability were good to excellent (ICC2,1 = 0.62–0.94). Minimal detectable change for the TE-LSA total score was 20 points. Standardized response means were large for worsened (0.88), moderate for improved (0.68), and trivial for stable participants (0.04). Completion rate was 100% and mean completion time was 5.5 ± 3.3 min. No ceiling or floor effects were observed for the TE-LSA total score.

Discussion and Implications

Telephone administration of the LSA is valid, reliable, responsive, and feasible for assessing LSM in community-dwelling older adults.
Inequalities in end-stage renal disease: underprivileged and ethnic minority members are at higher risk
Authors: Wilf-Miron Rachel , Myers Vicki , Saban Mor , Novikov Ilya , Kimron Lizie , Ziv Arnona , Kalter-Leibovici Ofra
Published: April 2023

Background

Incidence of end-stage renal disease (ESRD) is higher in Israel than the European average. Socio-economic differences in ESRD have been reported globally, but many countries lack a national register. Using national data, we assessed which socio-demographic factors are associated with 5-year incidence of ESRD in Israel, where there is universal access to renal replacement therapy (RRT).

Methods

Data on all incident ESRD cases aged ≥20 years receiving chronic RRT between 1 January 2014 and 31 December 2018 (N = 7883) were collected from Israel’s National Dialysis & Renal Transplant Register. Individual-level data on ESRD cases requiring RRT included residential area, age, gender, ethnicity (Jewish or Arab) and ESRD cause (diabetes, other, unknown/missing). Area-level data included age and sex distribution, socio-economic status (SES) and proportion of Arab population. The associations between individual-level socio-demographic characteristics and ESRD cause were tested in bivariate comparisons. The risk of developing ESRD during the study period (from all and specific causes) was estimated using multiple Poisson regression models with negative binomial distribution, using four parameters, namely sex, ethnicity, SES category and age strata, based on area-level distribution of these parameters, and with the whole population (aged ≥20 years) as the denominator.

Results

A socio-economic gradient was seen for ESRD from all causes, more marked for diabetic aetiology [rate ratio (RR)=0.45, 95% CI: 0.39–0.52 highest vs lowest SES categories] than from other (RR = 0.64, 95% CI: 0.55–0.75) or unknown cause (RR = 0.79, 95% CI: 0. 62–0.99). Based on population area-level data, predominantly Arab neighbourhoods showed higher risk for ESRD requiring RRT for all causes, with the strongest association for diabetes (RR = 1.69, 95% CI: 1.53–1.86) adjusted for SES, age and sex.

Conclusions

A strong socio-economic gradient was demonstrated for ESRD requiring RRT. Arab ethnicity was associated with higher risk for ESRD, especially due to diabetes. Our findings suggest the need for allocation of health resources according to needs and culturally appropriate interventions for improving control of modifiable risk factors for chronic renal failure.
Efficacy of vancomycin lock therapy for totally implantable venous access port-related infection due to coagulase-negative staphylococci in 100 patients with cancer
Authors: Lafaurie Matthieu , Montlahuc Claire , Kerneis Solen , de Lastours Victoire , Abgrall Sophie , Manceron Véronique , Couzigou Carine , Chabrol Amélie , de Raigniac Axelle , Lescure Xavier , Longuet Pascale , Lesprit Philippe , Vanjak Dominique , Lepeule Raphael ,   Groupe des référents en Infectiologie d’Ile de France (GRIF), Abgrall S , Bleibtreu A , Canoui E , Caseris M , Chabrol A , Chopin D , Couzigou C , De Coninck L , Diamantis S , Dournon N , Dubert M , Dollat M , Escaut L , Fihman V , Galy A , Gros H , Kerneis S , Lafaurie M , de Lastours V , Lebeaux D , L Lecapitaine A , Lefort A , Lepeule R , Longuet P , Munier A L , Ourghanlian C , Pourbaix A , de Raigniac A , Saidani M , Sayne N , Surgers L , Therby A , Wemmert C
Published: April 2023

Objectives

Data on the efficacy of vancomycin catheter lock therapy (VLT) for conservative treatment of totally implantable venous access port-related infections (TIVAP-RI) due to CoNS are scarce. The aim of this study was to evaluate the effectiveness of VLT in the treatment of TIVAP-RI due to CoNS in cancer patients.

Methods

This prospective, observational, multicentre study included adults with cancer treated with VLT for a TIVAP-RI due to CoNS. The primary endpoint was the success of VLT, defined as no TIVAP removal nor TIVAP-RI recurrence within 3 months after initiation of VLT. The secondary endpoint was 3 month mortality. Risk factors for VLT failure were also analysed.

Results

One hundred patients were included [men 53%, median age 63 years (IQR 53–72)]. Median duration of VLT was 12 days (IQR 9–14). Systemic antibiotic therapy was administered in 87 patients. VLT was successful in 44 patients. TIVAP could be reused after VLT in 51 patients. Recurrence of infection after completion of VLT occurred in 33 patients, among which TIVAP was removed in 27. Intermittent VLT (antibiotic solution left in place in the TIVAP lumen part of the time) was identified as a risk factor for TIVAP-RI recurrence. At 3 months, 26 deaths were reported; 1 (4%) was related to TIVAP-RI.

Conclusions

At 3 months, success of VLT for TIVAP-RI due to CoNS was low. However, removing TIVAP was avoided in nearly half the patients. Continuous locks should be preferred to intermittent locks. Identifying factors of success is essential to select patients who may benefit from VLT.
The antioxidant defence ofDekkera bruxellensisagainst hydrogen peroxide and its relationship to nitrate metabolism
Authors: Xavier Mariana Rodrigues , Teles Gilberto Henrique , de Carvalho Jennyfer Martins , Vieira Leucio Duarte , Pita Will de Barros , Antonio de Morais Marcos
Published: April 2023

Aims. The yeast Dekkera bruxellensis is a Crabtree-positive yeast that tends towards the oxidative/respiratory metabolism in aerobiosis. However, it is more sensitive to H2O2 than Saccharomyces cerevisiae. In order to investigate this metabolic paradox, the present work aimed to uncover the biological defence mechanism used by this yeast to tolerate the presence of exogenous H2O2. Methods and Results. Growth curves and spot tests were performed to establish the values of minimal inhibitory concentration and minimal biocidal concentration of H2O2 for different combinations of carbon and nitrogen sources. Cells in exponential growth phase in different culture conditions were used to measure superoxide and thiols [protein (PT) and non-PT], enzyme activities and gene expression. Conclusions. The combination of glutathione peroxidase (Gpx) and sulfhydryl-containing PT formed the preferred defence mechanism against H2O2, which was more efficiently active under respiratory metabolism. However, the action of this mechanism was suppressed when the cells were metabolizing nitrate (NO3). Significance and Impact of Study. These results were relevant to figure out the fitness of D. bruxellensis to metabolize industrial substrates containing oxidant molecules, such as molasses and plant hydrolysates, in the presence of a cheaper nitrogen source such as NO3.
Gustation in insects: taste qualities and types of evidence used to show taste function of specific body parts
Authors: King B H , Gunathunga Panchalie B
Published: April 2023

The insect equivalent of taste buds are gustatory sensilla, which have been found on mouthparts, pharynxes, antennae, legs, wings, and ovipositors. Most gustatory sensilla are uniporous, but not all apparently uniporous sensilla are gustatory. Among sensilla containing more than one neuron, a tubular body on one dendrite is also indicative of a taste sensillum, with the tubular body adding tactile function. But not all taste sensilla are also tactile. Additional morphological criteria are often used to recognize if a sensillum is gustatory. Further confirmation of such criteria by electrophysiological or behavioral evidence is needed. The five canonical taste qualities to which insects respond are sweet, bitter, sour, salty, and umami. But not all tastants that insects respond to easily fit in these taste qualities. Categories of insect tastants can be based not only on human taste perception, but also on whether the response is deterrent or appetitive and on chemical structure. Other compounds that at least some insects taste include, but are not limited to: water, fatty acids, metals, carbonation, RNA, ATP, pungent tastes as in horseradish, bacterial lipopolysaccharides, and contact pheromones. We propose that, for insects, taste be defined not only as a response to nonvolatiles but also be restricted to responses that are, or are thought to be, mediated by a sensillum. This restriction is useful because some of the receptor proteins in gustatory sensilla are also found elsewhere.
Exact Monte Carlo likelihood-based inference for jump-diffusion processes
Authors: Gonçalves Flávio B , Łatuszyński Krzysztof , Roberts Gareth O
Published: April 2023

Statistical inference for discretely observed jump-diffusion processes is a complex problem which motivates new methodological challenges. Thus, existing approaches invariably resort to time-discretisations which inevitably lead to approximations in inference. In this paper, we give the first general collection of methodologies for exact (in this context meaning discretisation-free) likelihood-based inference for discretely observed finite activity jump-diffusions. The only sources of error involved are Monte Carlo error and convergence of expectation maximisation (EM) or Markov chain Monte Carlo (MCMC) algorithms. We shall introduce both frequentist and Bayesian approaches, illustrating the methodology through simulated and real examples.