bluuebunny/crossref_metadata_2025 huggingface dataset:
Adeno‐associated virus serotype 2 capsid variants for improved liver‐directed gene therapy
Authors: Meumann Nadja , Cabanes‐Creus Marti , Ertelt Moritz , Navarro Renina Gale , Lucifora Julie , Yuan Qinggong , Nien‐Huber Karin , Abdelrahman Ahmed , Vu Xuan‐Khang , Zhang Liang , Franke Ann‐Christin , Schmithals Christian , Piiper Albrecht , Vogt Annabelle , Gonzalez‐Carmona Maria , Frueh Jochen T. , Ullrich Evelyn , Meuleman Philip , Talbot Steven R. , Odenthal Margarete , Ott Michael , Seifried Erhard , Schoeder Clara T. , Schwäble Joachim , Lisowski Leszek , Büning Hildegard
Published: August 2022

Background and Aims:

Current liver‐directed gene therapies look for adeno‐associated virus (AAV) vectors with improved efficacy. With this background, capsid engineering is explored. Whereas shuffled capsid library screenings have resulted in potent liver targeting variants with one first vector in human clinical trials, modifying natural serotypes by peptide insertion has so far been less successful. Here, we now report on two capsid variants, MLIV.K and MLIV.A, both derived from a high‐throughput in vivo AAV peptide display selection screen in mice.

Approach and Results:

The variants transduce primary murine and human hepatocytes at comparable efficiencies, a valuable feature in clinical development, and show significantly improved liver transduction efficacy, thereby allowing a dose reduction, and outperform parental AAV2 and AAV8 in targeting human hepatocytes in humanized mice. The natural heparan sulfate proteoglycan binding ability is markedly reduced, a feature that correlates with improved hepatocyte transduction. A further property that might contribute to the improved transduction efficacy is the lower capsid melting temperature. Peptide insertion also caused a moderate change in sensitivity to human sera containing anti‐AAV2 neutralizing antibodies, revealing the impact of epitopes located at the basis of the AAV capsid protrusions.

Conclusions:

In conclusion, MLIV.K and MLIV.A are AAV peptide display variants selected in immunocompetent mice with improved hepatocyte tropism and transduction efficiency. Because these features are maintained across species, MLIV variants provide remarkable potential for translation of therapeutic approaches from mice to men.
Ecological interface design and emergent users: Designing for small‐scale trucking ecology in India
Authors: Kant Vivek , Karthikeyan Varun V. , Sharma Nishant
Published: August 2022

Effective on‐road safety requires proper maintenance of vehicles. In the trucking sector in India, there is a need for supporting predictive maintenance to decrease downtime and improve safety. Improving maintenance in this sector involves certain challenges. First, most trucks are owned by small‐scale fleet owners (trucks < 5). Second, maintenance is often handled by small‐scale mechanic workshops. The fault diagnosis is very often limited to recognition by the driver and later reassessed by the mechanic by relying on the feel or the sound of the vehicle. Third, a majority of stakeholders in this sector—drivers, mechanics, and owners—have low levels of education. Despite these challenges, with the increase in the rate of digitalization, in the future, it will be easier to monitor the health of the parts of a truck. In addition, there is a developing trend of mobile phone and internet penetration in India that has leapfrogged a majority of Indians into becoming “emergent users” of information technology. Therefore, this article shows that sociotechnical approaches such as ecological interface design can be used to develop mobile interfaces for supporting predictive maintenance through health and usage monitoring of trucks for small‐scale fleet owners in India. To develop the interface, a field study was conducted at several sites in the state of Tamil Nadu, India. The insights were used to develop scenarios and the abstraction hierarchy, which were later used creatively to develop the interface design for emergent users.
Ibrutinib combined with low‐dose histone deacetylases inhibitor chidamide synergistically enhances the anti‐tumor effect in B‐cell lymphoma
Authors: Yu Hui , Mi Lan , Zhang Weimin , Ye Yingying , Li Miaomiao , Hu Dingyao , Cao Jiaowu , Wang Dedao , Wang Xiaogan , Ding Ning , Song Yuqin , Zhu Jun
Published: August 2022

Aberrant activity of histone deacetylases (HDACs) is frequently detected in B‐cell lymphomas, which indicated the therapeutic implications of HDAC inhibitors for B‐cell malignancies. We have discovered that lymphoma cells treated with HDAC inhibitor presented with activation of Bruton tyrosine kinase (BTK) which played an important role in the development of B‐cell malignancies. Therefore, our study intended to explore whether the addition of ibrutinib (BTK inhibitor) to chidamide (HDAC inhibitor) could generate combined anti‐tumor effects in B‐cell lymphomas. Using cell viability assay, cell cycle and apoptosis kit, we demonstrated an evident synergistic action of ibrutinib and chidamide in inhibiting tumor cell proliferation and motility. Consistent with in vitro data, the synergistic anti‐tumor effects were also observed in multiple tumor‐bearing mice models. By performing RNA‐seq and flow cytometry of tumor tissue, the enhancement of anti‐tumor immunity was observed with the co‐treatment of chidamide and ibrutinib. Together, these mechanistic insights indicated that simultaneously targeting BTK and HDAC could be a promising clinical therapy for B‐cell lymphomas.
Normal but skewed?
Authors: Amengual Dante , Bei Xinyue , Sentana Enrique
Published: August 2022

We propose a multivariate normality test against skew normal distributions using higher‐order log‐likelihood derivatives, which is asymptotically equivalent to the likelihood ratio but only requires estimation under the null. Numerically, it is the supremum of the univariate skewness coefficient test over all linear combinations of the variables. We can simulate its exact finite sample distribution for any multivariate dimension and sample size. Our Monte Carlo exercises confirm its power advantages over alternative approaches. Finally, we apply it to the joint distribution of US city sizes in two consecutive censuses finding that non‐normality is very clearly seen in their growth rates.
Development of an acellular nerve cap xenograft for neuroma prevention
Authors: Faust Anne E. , Soletti Lorenzo , Cwalina Nicole A. , Miller Andrew D. , Wood Matthew D. , Mahan Mark A. , Cheetham Jonathan , Brown Bryan N.
Published: August 2022

Neuroma formation following limb amputation is a prevalent and debilitating condition that can deeply affect quality of life and productivity. Several approaches exist to prevent or treat neuromas; however, no approach is either consistently reliable or surgically facile, with high rates of neuroma occurrence and/or recurrence. The present study describes the development and testing of a xenogeneic nerve cap graft made from decellularized porcine nerve. The grafts were tested in vitro for cellular removal, cytotoxicity, mechanical properties, and morphological characteristics. The grafts were then tested in rat sciatic nerve gap reconstruction and nerve amputation models for 8 weeks. Gross morphology, electrophysiology, and histopathology assessments were performed to determine the ability of the grafts to limit pathologic nerve regrowth. In vitro testing showed well decellularized and demyelinated nerve cap graft structures without any cytotoxicity from residual reagents. The grafts had a proximal socket for the proximal nerve stump and longitudinally oriented internal pores. Mechanical and surgical handling properties suggested suitability for implantation as a nerve graft. Following 8 weeks in vivo, the grafts were well integrated with the proximal and distal nerve segments without evidence of fibrotic adhesions to the surrounding tissues or bulbous outgrowth of the nerve. Electrophysiology revealed absence of nerve conduction within the remodeled nerve cap grafts and significant downstream muscle atrophy. Histologic evaluation showed well organized but limited axonal regrowth within the grafts without fibrous overgrowth or neuromatous hypercellularity. These results provide proof of concept for a novel xenograft‐based approach to neuroma prevention.
Collagen membrane from bovine pericardium for treatment of long bone defect
Authors: Yamanaka Jéssica S. , Oliveira Ana Clara , Bastos Ana Raquel , Fernandes Emanuel M. , Reis Rui L. , Correlo Vitor M. , Shimano Antônio Carlos
Published: August 2022

The treatment of bone regeneration failures has been constantly improved with the study of new biomaterials. Techgraft® is a collagen membrane derived from bovine pericardium, which has been shown to have biocompatibility and effectiveness in tissue repair. However, its use in orthopedics has not yet been evaluated. Therefore, the purpose of this study was to characterize a bovine pericardium collagen membrane and evaluate the effects of its use in the regeneration of a bone defect in rat tibia. Scanning electron microscopy, atomic force microscopy, weight lost and water uptake tests, and mechanical test were performed. Afterwards, the membrane was tested in an experimental study, using 12 male Sprague Dawley rats. A bone defect was surgically made in tibiae of animals, which were assigned to two groups (n = 6): bone defect treated with collagen membrane (TG) and bone defect without treatment (CONT). Then, tibiae were submitted to micro‐CT. The membranes preserved their natural collagen characteristics, presenting great strength, high water absorption, hydrophilicity, and almost complete dissolution in 30 days. In the experimental study, the membrane enhanced the growth of bone tissue in contact with its surface. A higher bone volume and trabeculae number and less trabecular space was observed in bone defects of the membrane group compared to the control group at 21 days. In conclusion, the Techgraft membrane seems to have favorable characteristics for treatment of long bone repair.
C5aR2 receptor: The genomic twin of the flamboyant C5aR1
Authors: Das Aurosikha , Gupta Pulkit K. , Rana Soumendra
Published: August 2022

The complement fragment C5a is one of the most potent proinflammatory glycoproteins liberated by the activation of the biochemical cascade of the complement system. C5a is established to interact with a set of genomically related transmembrane receptors, like C5aR1 (CD88, C5aR) and C5aR2 (GPR77, C5L2) with comparable affinity. The C5aR1 is a classical G‐protein‐coupled receptor (GPCR), whereas C5aR2 is a nonclassical GPCR that tailors immune cell activity potentially through β‐arrestins rather than G‐proteins. Currently, the exact function of the C5aR2 is actively debated in the context of C5aR1, even though both C5aR1 and C5aR2 are coexpressed on myriads of tissues. The functional relevance of C5aR2 appears to be context‐dependent compared to the C5aR1, which has received enormous attention for its role in both acute and chronic inflammatory diseases. In addition, the structure of C5aR2 and its interaction specificity toward C5a is not structurally elucidated in the literature so far. The current study has attempted to close the gap by generating highly refined model structures of C5aR2, respectively in free (inactive), complexed to C‐terminal peptide of C5a (meta‐active) and the C5a (active), embedded to a model palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine bilayer. The computational modeling and the 1.5‐μs molecular dynamics data presented in the current study are expected to further enrich the understanding of C5a–C5aR2 interaction compared to C5a–C5aR1, which will surely help in elaborating the currently debated biological function of C5aR2 better in the foreseeable future.
Test–retest stability, convergent validity, and sensitivity to change for the Goal‐Based Outcome tool for adolescents: Analysis of data from a randomized controlled trial
Authors: Duncan Charlie , Cooper Mick , Saxon David
Published: August 2022

Objective(s)

To examine the psychometric properties of the idiographic Goal‐Based Outcome (GBO) tool for young people: test–retest stability, convergent validity, and sensitivity to an intervention.

Methods

This measure validation study used data from a randomized controlled trial of school‐based humanistic counseling. We used multilevel analyses to assess test–retest stability, convergent validity of the GBO tool against nomothetic measures of mental wellbeing, and sensitivity to an intervention.

Results

The GBO tool showed acceptable stability over a 6–24 week period; moderate convergent validity with nomothetic measures of mental well‐being, self‐esteem, and depression; and greater sensitivity to an intervention than a measure of psychological distress.

Conclusions

The GBO tool shows evidence of having acceptable psychometric properties and is suitable for monitoring change on individual goals. It may also have the capacity to function as a population‐level indicator of outcomes in conjunction with the use of other measures of mental health and wellbeing.
Joint developmental trajectories and correlates of internalizing and externalizing problems among Chinese adolescents
Authors: Wang Shuo , Shi Xuliang , Wang Zhen , Li Zihan , Wang Anqi , Hu Xinhui , Li Zhipeng
Published: August 2022

Background

Internalizing and externalizing problems are the most prevalent health problems among adolescents. However, few studies have examined co‐occurring internalizing and externalizing problems from a longitudinal perspective.

Methods

A total of 1051 seventh‐grade students from two junior high schools were recruited at baseline. Among them, 932 valid participants were reassessed 1 year and 2 years later. Data were analyzed using parallel‐process latent class growth analysis and multinominal logistic regression.

Results

Four joint trajectories of internalizing and externalizing problems were identified. Compared with the low‐risk group, adolescents in the moderate and chronic co‐occurring group had lower resilience, higher levels of insecure attachment, family conflicts, and academic pressure. Adolescents in the pure internalizing group had higher levels of family conflicts and academic pressure compared with the low‐risk group.

Conclusions

Co‐occurrence of symptoms is very high in adolescents. More individualized intervention programs should be provided to these specific groups.
Drug Combination Modeling: Methods and Applications in Drug Development
Authors: Pearson Rachael A. , Wicha Sebastian G. , Okour Malek
Published: August 2022

Combination therapies have become increasingly researched and used in the treatment and management of complex diseases due to their ability to increase the chances for better efficacy and decreased toxicity. To evaluate drug combinations in drug development, pharmacokinetic and pharmacodynamic interactions between drugs in combination can be quantified using mathematical models; however, it can be difficult to deduce which models to use and how to use them to aid in clinical trial simulations to simulate the effect of a drug combination. This review paper aims to provide an overview of the various methods used to evaluate combination drug interaction for use in clinical trial development and a practical guideline on how combination modeling can be used in the settings of clinical trials.
Graphs of low average degree without independent transversals
Authors: Groenland Carla , Kaiser Tomáš , Treffers Oscar , Wales Matthew
Published: August 2022

An independent transversal of a graph with a vertex partition is an independent set of intersecting each block of in a single vertex. Wanless and Wood proved that if each block of has size at least and the average degree of vertices in each block is at most , then an independent transversal of exists. We present a construction showing that this result is optimal: for any and sufficiently large , there is a forest with a vertex partition into parts of size at least such that the average degree of vertices in each block is at most , and there is no independent transversal. This unexpectedly shows that methods related to entropy compression such as the Rosenfeld–Wanless–Wood scheme or the Local Cut Lemma are tight for this problem. Further constructions are given for variants of the problem, including the hypergraph version.
Planar Legendrian Θ ${\rm{\Theta }}$‐graphs
Authors: Lambert‐Cole Peter , O'Donnol Danielle
Published: August 2022

We classify topologically trivial Legendrian ‐graphs in and identify the complete family of nondestabilizable Legendrian realizations in this topological class. In contrast to all known results for Legendrian knots, this is an infinite family of graphs. We also show that any planar graph that contains a subdivision of a ‐graph or as a subgraph will have an infinite number of distinct, topologically trivial nondestabilizable Legendrian embeddings. Additionally, we introduce two moves, vertex stabilization and vertex twist, that change the Legendrian type within a smooth isotopy class.
Preoperative Diagnosis of Dual‐Phenotype Hepatocellular Carcinoma Using Enhanced MRI Radiomics Models
Authors: Wu Qian , Yu Yi‐xing , Zhang Tao , Zhu Wen‐jing , Fan Yan‐fen , Wang Xi‐ming , Hu Chun‐hong
Published: August 2022

Background

Dual‐phenotype hepatocellular carcinoma (DPHCC) is highly aggressive and difficult to distinguish from hepatocellular carcinoma (HCC).

Purpose

To develop and validate clinical and radiomics models based on contrast‐enhanced MRI for the preoperative diagnosis of DPHCC.

Study type

Retrospective.

Population

A total of 87 patients with DPHCC and 92 patients with non‐DPHCC randomly divided into a training cohort (n = 125: 64 non‐DPHCC; 61 DPHCC) and a validation cohort (n = 54: 28 non‐DPHCC; 26 DPHCC).

Field Strength/Sequence

A 3.0 T; dynamic contrast‐enhanced MRI with time‐resolved T1‐weighted imaging sequence.

Assessment

In the clinical model, the maximum tumor diameter and hepatitis B virus (HBV) were independent risk factors of DPHCC. In the radiomics model, a total of 1781 radiomics features were extracted from tumor volumes of interest (VOIs) in the arterial phase (AP) and portal venous phase (PP) images. For feature reduction and selection, Pearson correlation coefficient (PCC) and recursive feature elimination (RFE) were used. Clinical, AP, PP, and combined radiomics models were established using machine learning algorithms (support vector machine [SVM], logistic regression [LR], and logistic regression‐least absolute shrinkage and selection operator [LR‐LASSO]) and their discriminatory efficacy assessed and compared.

Statistical Tests

The independent sample t test, Mann–Whitney U test, Chi‐square test, regression analysis, receiver operating characteristic curve (ROC) analysis, Pearson correlation analysis, the Delong test. A P value < 0.05 was considered statistically significant.

Results

In the validation cohort, the combined radiomics model (area under the curve [AUC] = 0.908, 95% confidence interval [CI]: 0.831–0.985) showed the highest diagnostic performance. The AUCs of the PP (AUC = 0.879, 95% CI: 0.779–0.979) and combined radiomics models were significantly higher than that of clinical model (AUC = 0.685, 95% CI: 0.526–0.844). There were no significant differences in AUC between AP or PP radiomics model and combined radiomics model (P = 0.286, 0.180 and 0.543).

Conclusion

MRI radiomics models may be useful for discriminating DPHCC from non‐DPHCC before surgery.

Evidence Level

4

Technical Efficacy

Stage 2
Combined liver transplantation and sleeve gastrectomy: Report of a brief‐interval staged approach
Authors: Tariq Nabil , Saharia Ashish , Nwokedi Ugoeze , Hobeika Mark J. , Mobley Constance M. , Hsu David , Potter Lucy M. , Moore Linda W. , Elaileh Ahmed , Sherman Vadim , Ghobrial R. Mark
Published: August 2022

Pretransplantation bariatric surgery in patients with high Model for End‐Stage Liver Disease (MELD) score is fraught with risks. Bariatric surgery after liver transplantation (LT) may be complicated by surgical adhesions but could have advantages if performed at the time of transplantation. We investigated a method of brief‐interval staging combining LT and sleeve gastrectomy (SG). LT recipients with a body mass index (BMI) > 40 kg/m2 received an SG during the same hospitalization as the LT (LT/SG), at the same time as a planned brief‐interval return to the operating room for biliary anastomosis. Differences in intraoperative attributes of the LT (Stage 1) versus SG (Stage 2) procedures were analyzed using Wilcoxon signed‐rank test with significance p < 0.05 and compared with patients with obesity having a two‐stage LT without SG. A total of 14 cases {median MELD score 33 (interquartile range [IQR], 18–40)} were compared with 28 controls; 60% were critically ill prior to surgery with mechanical ventilation, vasopressors, or continuous renal replacement therapy. Median interval between procedures was 16.1 (IQR, 12.5–22.7) hours for cases and 12.2 (IQR, 11.1–16.6) hours for controls, p = 0.27. Median BMI at LT/SG was 47.0 (IQR, 41.7–51.3) kg/m2 versus 38.1 (IQR, 35.7–39.8) kg/m2 for controls, p < 0.001. At 1 year, median excess body weight loss was 74.0% (IQR, 46.2%–78.7%) in cases and 15.8% (IQR, −5.4% to 62.6%) in controls, p = 0.13; total weight loss was 38.1% (IQR, 23.9–42.9) in cases versus 7.7% (IQR, −2.4% to 27.6%) for controls, p = 0.03. Graft survival at 1 year was 92.9% for cases and 89.3% for controls with similar early postoperative outcomes. This proof‐of‐concept study revealed that a brief‐interval SG during LT is feasible in patients with high MELD and resulted in sustained weight loss at 1 year with similar graft survival. Further studies are needed to determine an optimal strategy.
Urinary parabens and breast cancer risk: Modification by LINE‐1 and LUMA global DNA methylation, and associations with breast cancer defined by tumor promoter methylation status
Authors: Parada Humberto , Sahrai Leili , Wolff Mary S. , Santella Regina M. , Chen Jia , Neugut Alfred I. , Teitelbaum Susan L.
Published: August 2022

Parabens are a group of alkyl esters of p‐hydroxybenzoic acid added to consumer products to prevent the growth of harmful bacteria and molds. Parabens are hypothesized to increase the risk of breast cancer (BC); however, no study has examined the interactions between parabens, global DNA methylation (DNAm), and BC risk. We examined the modifying effects of DNAm on the associations between parabens and BC, and whether parabens were associated with BC defined by tumor promoter methylation status. Participants included 708 cases and 598 controls from the Long Island Breast Cancer Study Project. Methylparaben (MPB), propylparaben, and butylparaben levels were measured in spot urine samples. Global DNAm was measured by analysis of long interspersed elementes‐1 (LINE‐1) and the luminometric methylation assay (LUMA). The promoter methylation status of 13 genes was measured in tumor samples from 509 cases. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between parabens and BC stratified by LINE‐1/LUMA, and between parabens and gene‐specific promoter methylation‐defined BC. Outcome heterogeneity was evaluated using ratios of ORs (RORs). We assessed the joint effects of the multiple parabens using quantile g‐computation. The highest versus lowest tertile of MPB and a one‐quantile increase in all parabens were associated with ORs of 1.46 (95% CI = 0.96–2.23) and 1.32 (95% CI = 1.02–1.71), respectively, among women with hypomethylated LINE‐1. A one‐ln unit increase in MPB was associated with a 25% increase in the odds of hypomethylated (vs. hypermethylated) CCND2 promoter‐defined BC (ROR = 1.25, 95% CI = 1.06–1.48), and a one‐quantile increase in all parabens was associated with a 55% increase in the odds of hypomethylated (vs. hypermethylated) CCND2 promoter‐defined BC (ROR = 1.55, 95% CI = 1.04–2.32). Exposure to parabens may increase the risk of BC among women with hypomethylated global DNAm and may increase the risk of tumors with gene‐specific hypomethylated promoter regions.
Performance evaluation of a high‐resolution regional model over West Africa for operational use: A case study of August 2017
Authors: Olaniyan Eniola A. , Cafaro Carlo , Ogungbenro Stephen B. , Gbode Imoleayo E. , Ajayi Vincent O. , Oluleye Ayodeji , Adefisan Elijah A. , Schwendike Juliane , Lawal Kamoru A.
Published: August 2022

The frequency of flash floods resulting from heavy rainfall over West Africa has increased in recent years with serious socio‐economic consequences. Therefore, the need to utilize numerical weather prediction models to forecast heavy rainfall events reliably is also rising at many operational meteorological centres in West Africa. This paper evaluates the performance of the Consortium for Small‐scale Modelling (COSMO) model of the German Meteorological Services (DWD) in predicting rainfall over West Africa for high‐impact rainfall events that occurred between 19 and 26 August 2017. The paper aims to investigate the synoptic forcings modulating daily rainfall variability during that period. Results show that COSMO simulates adequately the spatio‐temporal variability of rainfall distribution over West Africa, though with inherent biases. COSMO displays a decreasing skill in producing spatial rainfall distribution as rainfall amounts tend to 30 mm and above. Additionally, areas of heavy rainfall, mostly about 100–300 km southwest of the core of the Africa Easterly Jet (AEJ), often coincide with areas of decreasing mean sea level pressure of at least 0.6 hPa and areas of increasing convective available potential energy of at least 500 J/kg. Although not in all cases, the trough of the Africa Easterly Wave (AEW) is always located to the east of these areas. We show that not every storm, especially east of the prime meridian, is associated with an AEW trough. COSMO is able to reproduce the atmospheric dynamics modulating the daily rainfall variability, in addition to capturing the daily propagation of the AEW trough, and the core of the AEJ. However, the reproducibility skill of the model in predicting atmospheric dynamics may not transform into the predictive skill of the model in producing rainfall. Nevertheless, operational forecasters may be able to determine likely areas of heavy rainfall by estimating the position of the AEJ core based on the position of areas of the least falling pressure from COSMO. Finally, the incorporation of the fractions skill score metric based on the neighbourhood approach could also assist operational forecasters to decide at which scale a severe weather alert can be issued.
An Analysis of Barriers to the Implementation of an ISO Certified Quality Management System for National Meteorological and Hydrological Services in the Anglophone Caribbean
Authors: Mitchell Cécil , Fakhruddin Bapon (SHM)
Published: August 2022

Aeronautical Meteorological Offices under National Meteorological and Hydrological Service provide critical meteorological, hydrological, ocean and climatological information that sustain air navigation safety, efficiency, and regularity. Thus, to quality assure the information, the International Civil Aviation Organization recommended in 2002 that Aeronautical Meteorological Offices should implement ISO 9001 quality management system, which was subsequently standardized and became effective on 15 November 2012. There has been a slow movement towards adoption due to a number of barriers. In July 2019, 52% of Aeronautical Meteorological Offices commenced transition to the fifth iteration, ISO 9001:2015. A range of studies have investigated the barriers to successful quality management system implementation and certification within various organizations. However, only one study examined the Aeronautical Meteorological Offices and none of them covered the Anglophone Caribbean. Hence, the demography of the sample for this study is unique and this paper will contribute to filling the gaps in the literature. This exploratory study aims to identify the barriers, investigate their impacts, and propose recommendations to assist the Aeronautical Meteorological Offices to fully implement the ISO standard. Trinidad and Tobago Meteorological Service was selected as a case study due to its progress in the quality management system implementation and the scope of its operations. The study used and triangulated data collected from secondary sources (desktop research) and primary sources (survey and interviews). Seventeen barriers were identified and formed the new empirical framework for the Aeronautical Meteorological Offices in the Anglophone Caribbean. Most barriers were in the category of resources. The findings have significant implications for the policymakers, especially executive management, to address the barriers that are risks to sustainable quality management system.
Counting the nodules that count, relationships between seed nitrogen and root nodules
Authors: Zubrod Melinda
Published: August 2022

The nodules on the roots of soybeans provide N that the plant uses for growth and development. The goal of this study is to observe if the number of nodules on the taproot, volume of nodules on the taproot, the total number of nodules, or the number of nodules on the secondary roots in the early growth stages of soybeans have a significant correlation with the amount of elemental N in mature seed. The Soybean Nodule Acquisition Pipeline was used to quantify these traits and the mature seed was analyzed to obtain the amount of elemental N. The data set used for this project consisted of six genetically and phenotypically diverse soybean lines from two unique sites in 2018. Strong positive correlations were discovered between the number and volume of nodules on the taproot and the amount of N in mature seed. There was a less significant correlation between total nodule counts and N in mature seeds. There was not a strong significant correlation between nodules on the secondary roots and N in mature seeds.
Design of lightweight damping core for composite sandwich structure
Authors: Sun Zhaoyi , Mei Zhiyuan , Li Yu , Gong Huashuai , Wang Guorong , Wang Qingxin
Published: August 2022

The damping performance and lightweight design requirements of composite sandwich structure core were studied. A series of low density damping cores were prepared by blending epoxy/polyurethane graft copolymer (E‐g‐U) and epoxy/poly mercaptan block copolymer (E‐b‐M) with different contents of hollow glass beads (HGM). The damping properties, mechanical properties, density, and interface morphology of the core layer were studied. The damping response and flexure properties of the sandwich composite structure were studied by modal analysis and three‐point flexure test. The experimental results show that optimal damping performance of matrix appears at 60% E‐b‐M ratio, the peak loss factor is 0.88, and the damping temperature range covers −2 ~ 52°C. When the HGM content in the core is 10 phr, the density can be comparable to that of the buoyancy material. Under flexural load, the ultimate shear strength and shear modulus of the sandwich structure increase maximum at 15 phr and 10 phr, respectively. Compared with the unfilled HGM sample, the first three modal damping ratios of the sandwich structure are increased by 133.2%, 56.6%, and 56% by 10 phr damping core, respectively. The results are compared with those in other reference. The research shows that the design of lightweight damping core is expected to provide a core material selection for the vibration reduction of sandwich structures.
Examining facilitators and barriers to evidence‐based professional practice by mental health providers in schools
Authors: Flegge Lindsay G.
Published: August 2022

This exploratory study surveyed school mental health providers across the United States to examine their perception of the facilitators and the barriers to evidence‐based professional practice (EBPP) when offering mental health services to students in schools and to identify any group differences of these perceptions. A national sample of school counselors, school psychologists, and social workers (N= 303, 86.5% female) was surveyed using an original questionnaire. Results of the study identified 12 perceived facilitators to EBPP: educational and professional standards, continuing education training, graduate school training, personal theoretical orientation, publications from professional organizations, individual student needs, peer support from coworkers, providing supervision to other professionals, access to research, access to resources to provide specific programs and interventions, student preferences, and use of treatment plans. No perceived barriers to EBPP were identified when looking at the whole sample. However, an examination of specific groups within the study revealed two barriers: use of treatment plans and providing supervision to other professionals. Findings provide an updated understanding of perceived facilitators and barriers to EBPP and set the stage for future interventions targeting these factors. Implications and future research directions are discussed.
Color‐tunable room temperature phosphorescence mediated by host–guest chemistry and stimuli‐responsive polymer matrices
Authors: Wang Jun , Lou Xin‐Yue , Tang Jun , Yang Ying‐Wei
Published: August 2022

Color‐tunable room temperature phosphorescence (RTP) luminescent materials with stimuli‐responsive properties are highly desirable for practical applications, but the fundamental design principles still need further exploitation. Herein, we report on the extended red‐shifted multicolor RTP afterglow from blue to orange, including white light, offered by a series of newly designed supramolecular polymers based on 1‐([2‐methylallyl]oxy)pyrene phosphor‐containing guest polymers and β‐cyclodextrin (β‐CD)/γ‐CD host molecules. RTP enhancement is efficiently realized, attributing to the strong restriction on the dimeric pyrene units by the host–guest inclusion complexation of CDs and the multiple interactions amongst polymer matrices and phosphorescent moieties. Interestingly, a more comprehensive blue‐shifted color tuning range is also enabled upon introducing pH‐sensitive fragments due to the self‐assembly of the ternary polymers aided by ionic bonding. Notably, optimized intelligent multicolor RTP systems induced by altered external stimuli, including concentration, irradiation, and pH, are established, showing great potential in developing stimuli‐responsive luminescent materials for practical applications. In addition, theoretical calculations are conducted to elucidate diverse emission mechanisms of pyrene units in different assembly states.
Patient adherence to physical activity advice (PAPA) in patients with low back pain: Study protocol for a multicentre randomized controlled trial
Authors: van Koppen Ben , Zandwijk Pim , van Mameren Henk , de Bie Rob
Published: August 2022

Background

It seems that nonspecific low back pain (NSLBP) cannot be successfully treated with a single intervention of any kind. However, a positive effect of an active lifestyle including physical activities in NSLBP is reported on pain and disability. Advising regular physical activity is one of the mainstays in physical therapy treatment, appealing to patients' adherence. Many patients with low back pain do not seem to adhere to their physiotherapist's advice. In this study, the influence of social support on adherence to an activity advice will be investigated.

Objective

Objective of the study is to investigate if patients with low back pain randomised to receive social support adhere better to an activity advice than patients randomised to the control group.

Methods

In a randomized controlled clinical trial, in private physiotherapy practices in the Netherlands, patients ≥18 years presenting with at least a second episode of nonspecific low back pain will be randomized over two groups: activity advice and social support as an add‐on to usual care versus usual care alone. The primary outcome measure is adherence to an activity advice measured by an activity monitor at 1, 6 and 12 weeks. All other objectives will be measured by questionnaires.

Discussion

This project is the first comprehensive research project to assess whether social support influences adherence to an activity advice outside the clinical setting without supervision of a healthcare provider. Where evidence of influence on social support is lacking, findings may have implications for the management of patients with low back pain. In addition, findings may enable physiotherapists to predict in which patients with low back pain an activity advice with social support makes sense.

ClinicalTrial.gov

NCT02996955.
Comparison of treatments with ordinal responses in trials with sequential monitoring and response‐adaptive randomization
Authors: Yu Yian , Xu Cong , Zhong Junjiang , Cheung Siu Hung
Published: August 2022

In clinical trials, comparisons of treatments with ordinal responses are frequently conducted using the proportional odds model. However, the use of this model necessitates the adoption of the proportional odds assumption, which may not be appropriate. In particular, when responses are skewed, the use of the proportional odds model may result in a markedly inflated type I error rate. The latent Weibull distribution has recently been proposed to remedy this problem, and it has been demonstrated to be superior to the proportional odds model, especially when response‐adaptive randomization is incorporated. However, there are several drawbacks associated with the latent Weibull model and the previously suggested response‐adaptive treatment randomization scheme. In this paper, we propose the modified latent Weibull model to address these issues. Based on the modified latent Weibull model, the original response‐adaptive design was also revised. In addition, the group sequential monitoring mechanism was included to enable interim analyses to be performed to determine, during a trial, whether a specific treatment is significantly more effective than another. If so, this will enable the trial to be terminated at a much earlier stage than a trial based on a fixed sample size. We performed a simulation study that clearly demonstrated the merits of our proposed framework. Furthermore, we redesigned a clinical study to further illustrate the advantages of our response‐adaptive approach.
What is liberal about Adam Smith's “liberal plan”?
Authors: Matson Erik W.
Published: August 2022

By the middle of the eighteenth century the word “liberal” had had multiple non‐political meanings. Adam Smith famously advances “the liberal plan” of political economy. InThe Wealth of Nationshe indicates several ways that his liberal plan is “liberal” in a non‐political sense. The liberal plan leads to economic growth, which leads to a rise in real wages and population through an extending division of labor. The liberal plan facilitates market integration, leading toward a distribution of food supplies that could be called liberal and generous if it was brought about by design of a distributor. The liberal plan entails a generous view of the person that dignifies the mundane and elevates ordinary work. Considering ways that Smith's liberal plan is “liberal” shines light on the soul of classical liberal political economy.
Effectiveness of screening endoscopy for esophageal squamous cell carcinoma in Japanese males
Authors: Nezu Yasuko , Manabe Noriaki , Yoda Yoshioki , Haruma Ken
Published: August 2022

Background

Esophageal squamous cell carcinoma (ESCC) has a poor prognosis; therefore, early detection is essential. In Japan, more than 90% of esophageal cancers are ESCC. Endoscopy is effective to detect ESCC in the early stage, but there is a limited number of reports examining its efficacy and effectiveness.

Objective

This study aimed to evaluate the efficacy of screening endoscopy for detecting ESCC.

Methods

This retrospective study analyzed the prevalence of ESCC, annual transition of prevalence, and the stage of each ESCC among 128,520 medical check‐up patients who underwent esophagogastroduodenoscopy from April 2015 to March 2020 at Yamanashi Koseiren Health Care Center. Furthermore, a case‐control study utilized the multivariate logistic regression analysis was performed to assess the risk factor of ESCC.

Results

Among a total of 128,520 subjects, 42 ESCC patients were detected, with 95.2% being diagnosed at early stages. Annual prevalence in males was 0.015% (2/13,122) in 2015, 0.044% (6/13,562) in 2016, 0.044% (6/13,676) in 2017, 0.074% (10/13,488) in 2018%, and 0.11% (16/14,386) in 2019. ESCC prevalence has been increasing each year. A significant increase was observed between 2015 and 2018 (p = 0.039). ESCC prevalence was 0.102% (25/24,272) when focusing on males aged over 50 years with a history of smoking and drinking. Regarding the case‐control study, the multivariate logistic regression analysis revealed smoking (p = 0.044), mean corpuscular volume (MCV) (p = 0.0018), and severe gastric atrophy (p = 0.048) as positively correlated with ESCC.

Conclusion

In conclusion, ESCC has been increasing in our center from 2015 to 2019, and the prevalence has been approaching that of gastric cancer in 2019 in male subjects. ESCC can be detected efficiently by targeting males with high MCV who have a history of drinking and smoking.
Gluonic evanescent operators: classification and one-loop renormalization
Authors: Jin Qingjun , Ren Ke , Yang Gang , Yu Rui
Published: August 2022

Abstract

Evanescent operators are a special class of operators that vanish classically in four-dimensional spacetime, while in general dimensions they are non-zero and are expected to have non-trivial physical effects at the quantum loop level in dimensional regularization. In this paper we initiate the study of evanescent operators in pure Yang-Mills theory. We develop a systematic method for classifying and constructing thed-dimensional Lorentz invariant evanescent operators, which start to appear at mass dimension ten. We also compute one-loop form factors for the dimension-ten operators via thed-dimensional unitarity method and obtain their one-loop anomalous dimensions. These operators are necessary ingredients in the study of high dimensional operators in effective field theories involving a Yang-Mills sector.
Impact of Sommerfeld effect and bound state formation in simplified t-channel dark matter models
Authors: Becker Mathias , Copello Emanuele , Harz Julia , Mohan Kirtimaan A. , Sengupta Dipan
Published: August 2022

Abstract

The existence of a dark matter model with a rich dark sector could be the reason why WIMP dark matter has evaded its detection so far. For instance, colored coannihilation naturally leads to the prediction of heavier dark matter masses. Importantly, in such a scenario the Sommerfeld effect and bound state formation must be considered in order to accurately predict the relic abundance. Based on the example of the currently widely studied t-channel simplified model with a colored mediator, we demonstrate the importance of considering these non-perturbative effects for correctly inferring the viable model parameters. We emphasize that a flat correction factor on the relic abundance is not sufficient in this context. Moreover, we find that parameter space thought to be excluded by direct detection experiments and LHC searches remains still viable. Additionally, we illustrate that long-lived particle searches and bound-state searches at the LHC can play a crucial role in probing such a model. We demonstrate how future direct detection experiments will be able to close almost all of the remaining window for freeze-out production, making it a highly testable scenario.
Tensor network approach to electromagnetic duality in (3+1)d topological gauge models
Authors: Delcamp Clement
Published: August 2022

Abstract

Given the Hamiltonian realisation of a topological (3+1)d gauge theory with finite group G, we consider a family of tensor network representations of its ground state subspace. This family is indexed by gapped boundary conditions encoded into module 2-categories over the input spherical fusion 2-category. Individual tensors are characterised by symmetry conditions with respect to non-local operators acting on entanglement degrees of freedom. In the case of Dirichlet and Neumann boundary conditions, we show that the symmetry operators form the fusion 2-categories 2VecG of G-graded 2-vector spaces and 2Rep(G) of 2-representations of G, respectively. In virtue of the Morita equivalence between 2VecG and 2Rep(G) — which we explicitly establish — the topological order can be realised as the Drinfel’d centre of either 2-category of operators; this is a realisation of the electromagnetic duality of the theory. Specialising to the case G = ℤ2, we recover tensor network representations that were recently introduced, as well as the relation between the electromagnetic duality of a pure ℤ2 gauge theory and the Kramers-Wannier duality of a boundary Ising model.
New Constructions of Exceptional Simple Lie Superalgebras with Integer Cartan Matrix in Characteristics 3 and 5 via Tensor Categories
Authors: Kannan Arun S.
Published: August 2022

Using tensor categories, we present new constructions of several of the exceptional simple Lie superalgebras with integer Cartan matrix in characteristic p = 3 and p = 5 from the complete classification of modular Lie superalgebras with indecomposable Cartan matrix and their simple subquotients over algebraically closed fields by Bouarroudj, Grozman, and Leites in 2009. Specifically, let αp denote the kernel of the Frobenius endomorphism on the additive group scheme $\mathbb {G}_{a}$

G

a

over an algebraically closed field of characteristic p. The Verlinde category Verp is the semisimplification of the representation category Repαp, and Verp contains the category of super vector spaces as a full subcategory. Each exceptional Lie superalgebra we construct is realized as the image of an exceptional Lie algebra equipped with a nilpotent derivation of order at most p under the semisimplification functor from Repαp to Verp.
Können Mesh-Vernebler die prähospitale Aerosoltherapie verbessern? Eine In-vitro-Studie an simulierten Notfallpatient*innen mit Atemnot
Authors: Otto M. , Kropp Y. , Kummer L. , Thiel M. , Tsagogiorgas C.
Published: August 2022

Hintergrund

Medikamentenvernebler im Rettungsdienst sollten eine hohe Vernebelungsleistung haben, um schnell eine therapeutische Wirkstoffkonzentration des vernebelten Medikaments zu erreichen. Eine Umfrage im süddeutschen Rettungsdienst zeigte allerdings, dass fast ausschließlich die wenig effizienten Jet-Vernebler zum Einsatz kommen.

Ziel der Arbeit

Ziel der vorliegenden In-vitro-Studie war es herauszufinden, ob der Einsatz von Mesh-Verneblern die prähospitale Aerosoltherapie verbessern könnte.

Material und Methoden

Die Vernebelungsleistung eines Jet-Verneblers (Cirrus™ 2, Fa. Intersurgical®) und 2 mobil einsatzbarer Mesh-Vernebler (Aerogen Solo®, Fa. Aerogen Limited, M‑Neb® mobile, NEBU-TEC International med. Produkte Eike Kern GmbH) wurde in einem In-vitro-Modell spontan atmender Notfallpatient*innen mit 4 unterschiedlichen Atemmustern bei verschiedenen Sauerstoffflussraten getestet.

Ergebnisse

Die Mesh-Vernebler zeigten im Vergleich zum Jet-Vernebler eine signifikant höhere Verneblungsleistung und Salbutamol-Filterdeposition, wobei der M‑Neb® mobile die höchsten Werte für Leistung und Deposition erreichte. Der Sauerstofffluss hatte den größten Einfluss auf die Leistung des Jet-Verneblers, wirkte sich aber kaum auf die Mesh-Vernebler aus. Die Deposition wurde zudem stark vom Atemmuster beeinflusst.

Diskussion

Der Einsatz von Mesh-Verneblern mit hoher Verneblungsleistung konnte in einem In-vitro-Modell die Aerosoltherapie von prähospitalen Notfallpatient*innen verbessern. Sie waren dem Jet-Vernebler in Bezug auf die Verneblungsleistung und die Lungendeposition überlegen und ermöglichten zudem eine bedarfsangepasste Sauerstofftherapie. Die höchste Medikamentendeposition wurde bei den tachypnoischen Patient*innen erreicht, welche in der praktischen Anwendung auch am meisten von einem erhöhten Medikamentenspiegel profitieren würden.