bluuebunny/crossref_metadata_2025 huggingface dataset:
Convergent Within-Host Adaptation of Pseudomonas aeruginosa through the Transcriptional Regulatory Network
Authors: Gatt Yair E. , Savion Dana , Bamberger Tal , Margalit Hanah
Published: March 2023

Pseudomonas aeruginosa
causes significant morbidity and mortality. The pathogen's remarkable ability to establish chronic infections greatly depends on its adaptation to the host environment.
Effective Colonization by Nontoxigenic Clostridioides difficile REA Strain M3 (NTCD-M3) Spores following Treatment with Either Fidaxomicin or Vancomycin
Authors: Sambol Susan P. , Skinner Andrew M. , Serna-Perez Fidel , Owen Benjamin , Gerding Dale N. , Johnson Stuart
Published: March 2023

NTCD-M3 is a novel live biotherapeutic, that has been shown in a Phase 2 clinical trial to prevent recurrence of
C. difficile
infection (CDI) when administered shortly after antibiotic treatment of the initial CDI episode. Fidaxomicin was not, however, in widespread use at the time this study was conducted.
Epidemiological Description and Detection of Antimicrobial Resistance in Various Aquatic Sites in Marseille, France
Authors: El-Sawalhi Sabah , Revol Océane , Chamieh Amanda , Lacoste Alexandre , Annessi Alexandre , La Scola Bernard , Rolain Jean-Marc , Pagnier Isabelle
Published: March 2023

Antibiotic-resistant bacteria are involved in serious infections in humans. The dissemination of these bacteria in water, which is in close contact with human activities, is a serious problem, especially under the concept of One Health.
Building-Level Detection Threshold of SARS-CoV-2 in Wastewater
Authors: Rondeau Nicole C. , Rose Oliver J. , Alt Ellen R. , Ariyan Lina A. , Elikan Annabelle B. , Everard Jenna L. , Schreier Abigail R. , Tessler Maya E. , Tulinsky Grace H. , Vo Janet R. , Ray Caroline A. , Yang Cynthia Y. , Miranda JJ L. , Mailloux Brian J.
Published: March 2023

Diagnostic testing of sewage can detect levels of circulating viruses to help inform public health. Wastewater-based epidemiology has been particularly active during the COVID-19 pandemic to measure the prevalence of SARS-CoV-2.
Unique Tandem Repeats in the Inverted Terminal Repeat Regions of Monkeypox Viruses
Authors: Desingu Perumal Arumugam , Nagarajan K. , Sundaresan Nagalingam R.
Published: March 2023

The different groups of MPXVs contain unique tandem repeats with different copy numbers in the ITR regions, and these repeats may be likely to play a role in the genetic diversity of the virus. Clade IIb (B) MPXV contains 38 and 32 repeats similar to the Tandem repeats reported in the human and rodent genome, respectively.
Influenza in Liver and Kidney Transplant Recipients: Incidence and Outcomes
Authors: Arentoft Nicoline Stender , Møller Dina Leth , Knudsen Andreas Delhbæk , Abdulovski Ranya , Kirkby Nikolai , Sørensen Søren Schwartz , Rasmussen Allan , Nielsen Susanne Dam
Published: March 2023

Influenza is a common respiratory virus in solid organ transplant recipients that may have severe complications, including pneumonia and hospitalization. This study investigates the incidence, risk factors, and complications of influenza in a Danish cohort of kidney and liver transplant recipients over 10 consecutive influenza seasons.
Genomic Analysis of Vancomycin-Resistant Staphylococcus aureus Isolates from the 3rd Case Identified in the United States Reveals Chromosomal Integration of the
vanA
Locus
Authors: Haas Wolfgang , Singh Navjot , Lainhart William , Mingle Lisa , Nazarian Elizabeth , Mitchell Kara , Nattanmai Geetha , Kohlerschmidt Donna , Dickinson Michelle C. , Kacica Marilyn , Dumas Nellie , Musser Kimberlee A.
Published: March 2023

High-level vancomycin-resistant
Staphylococcus aureus
(VRSA) began to emerge in the United States in 2002 and has since then been reported worldwide. Our study reports the closed genome sequences of multiple VRSA isolates obtained in 2004 from a single patient in New York State.
A New Potential Resource in the Fight against Candida auris: the
Cinnamomum zeylanicum
Essential Oil in Synergy with Antifungal Drug
Authors: Di Vito M. , Garzoli S. , Rosato R. , Mariotti M. , Gervasoni J. , Santucci L. , Ovidi E. , Cacaci M. , Lombarini G. , Torelli R. , Urbani A. , Sanguinetti M. , Bugli F.
Published: March 2023

This study highlights how small doses of CZ-EO are able to inhibit the secretion of fluconazole and promote its accumulation in the fungal cell. In this manner, the drug is able to exert its pharmacological effects bypassing the resistance of the yeast. If further studies will confirm this synergy, it will be possible to develop new therapeutic formulations active in the fight against
C. auris
resistances.
Type 2 Diabetes Mellitus- and Complication-Related Risk of Nontuberculous Mycobacterial Disease in a South Korean Cohort
Authors: Jeon Da Som , Kim Seonok , Kim Mi Ae , Chong Yong Pil , Shim Tae Sun , Jung Chang Hee , Kim Ye-Jee , Jo Kyung-Wook
Published: March 2023

We assessed whether patients with T2DM are at higher risk for incident NTM disease through analysis of NTM-naive matched cohorts from the data of a national population-based cohort which represents 2.2% of the total South Korean population. Although T2DM alone is not a statistically significant risk factor for NTM disease, T2DM significantly increases the risk of NTM disease in those with ≥2 diabetes-related complications.
Porcine Epidemic Diarrhea Virus nsp7 Inhibits MDA5 Dephosphorylation to Antagonize Type I Interferon Production
Authors: Zhang Jiansong , Fang Puxian , Ren Jie , Xia Sijin , Zhang Huichang , Zhu Xuerui , Ding Tong , Xiao Shaobo , Fang Liurong
Published: March 2023

Since late 2010, a reemerging porcine epidemic diarrhea virus variant with high pathogenesis has swept through most pig farms in many countries, resulting in significant economic losses. Coronavirus nonstructural protein 7 (nsp7), conserved within the family
Coronaviridae
, combines with nsp8 and nsp12 to form the viral replication and transcription complex that is indispensable for viral replication.
De novo monocytic-M5b AML with t(8;16) (p11.2; p13.3) KAT6A/CREBBP fusion and FLT3-TKD mutation complicated by chemotherapy-induced Takotsubo cardiomyopathy
Authors: Ananthaneni Anil , Benzar Taras , Hafiz Nazar , Akabane Hugo
Published: March 2023

Acute myeloid leukemia (AML) with t(8;16) is a rare cytogenetic abnormality that presents unique characteristics such as hemophagocytosis, disseminated intravascular coagulation, leukemia cutis and varying levels of CD45 expression. It is more common in women and usually associated with prior cytotoxic therapies, accounting for <0.5% of all AML cases. We present a case of de novo t(8;16) AML with FLT3-TKD mutation who relapsed after initial induction and consolidation. Mitelman database analysis reveals only 175 cases with this translocation, majority of which are M5 (54.3%) and M4 (21.1%) AML. Our review reveals very poor prognosis with overall survival ranging from 4.7 to 18.2 months. She also developed Takotsubo cardiomyopathy after receiving 7+3 induction regimen. Our patient died in 6 months from the date of diagnosis. Although a rare occurrence, it has been discussed in literature to identify t(8;16) as a separate subtype of AML due to unique characteristics.
Functional neurological disorder is a feminist issue
Authors: McLoughlin Caoimhe , Hoeritzauer Ingrid , Cabreira Verónica , Aybek Selma , Adams Caitlin , Alty Jane , Ball Harriet A , Baker Janet , Bullock Kim , Burness Chrissie , Dworetzky Barbara A , Finkelstein Sara , Garcin Béatrice , Gelauff Jeannette , Goldstein Laura H , Jordbru Anika , Huys Anne-Catherine ML , Laffan Aoife , Lidstone Sarah C , Linden Stefanie Caroline , Ludwig Lea , Maggio Julie , Morgante Francesca , Mallam Elizabeth , Nicholson Clare , O’Neal Mary , O‘Sullivan Suzanne , Pareés Isabel , Petrochilos Panayiota , Pick Susannah , Phillips Wendy , Roelofs Karin , Newby Rachel , Stanton Biba , Gray Cordelia , Joyce Eileen M , Tijssen Marina AJ , Chalder Trudie , McCormick Maxanne , Gardiner Paula , Bègue Indrit , Tuttle Margaret C , Williams Isobel , McRae Sarah , Voon Valerie , McWhirter Laura
Published: March 2023

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.
Micro-mechanical perspective on the role of particle shape in shearing of sands
Authors: Huo Y.X. , Leung Y.F. , Kwok C.Y.
Published: March 2023

This study presents a micro-mechanical perspective on the role of realistic particle shapes in shearing of sands through calibration with physical experiments and parametric studies using discrete element method (DEM) to reveal the different mechanics between irregular particles and spherical particles incorporating rolling resistance (μr). To achieve this goal, particle shapes of Toyoura sand were captured by micro-computed tomography and reconstructed using a clump generation algorithm in DEM. The use of clumps in DEM led to closer match with experimental results of triaxial tests at various porosities and confining pressures, which could not be achieved by sphere models with μr. With realistic particle shapes, initial rotations of clumps were allowed until they became interlocked, while the load resistance built up gradually. High coordination numbers were observed, with force chains relatively evenly distributed. In contrast, the use of μr in sphere models promoted the formation of voids that were sustained during the loading process, because rotational motions of particles were hampered by μr and they did not easily collapse into the voids. This was accompanied by polarised strong force network around the voids, leading to more dilative and brittle macroscopic behaviour than observed in physical experiments. These findings illustrate that particle shapes cannot be sufficiently replaced by the use of sphere models and μr due to intrinsic differences in their micro-mechanics.
EXPLORING FIRM INNOVATION CAPABILITY AS THE ‘BLACK BOX’ BETWEEN HUMAN CAPITAL AND PERFORMANCE IN RUSSIAN SMES
Authors: SELIVANOVSKIKH LOUISA
Published: March 2023

This study examines the mediating role of firm innovation capabilities as a strategic choice for Russian small and medium-sized enterprises (SMEs), which translates their managerial and worker human capital stocks into enhanced firm performance. The results of a survey conducted on 366 CEOs and business founders indicate innovation capabilities are the intermediate variable between firm human capital and SME performance. Further parallel mediation regression analysis demonstrates that human capital is positively and significantly related to all innovation capability dimensions (client-, marketing- and technology-focused); however, the mediation effect is significant only in the case of client-focused innovation capability–SMEs’ ability to provide clients with services that offer unique benefits, solve clients’ problems in innovative ways and seek out novel ways to tackle problems. These findings suggest that SMEs operating in turbulent transition economy environments can be more innovative and achieve the best performance using intangible, highly valuable and rare talent resources.
Rumor Detection on Social Media Using Deep Learning Algorithms with Fuzzy Inference System for Healthcare Analytics System Using COVID-19 Dataset
Authors: Rathakrishnan Akila , Sathiyanarayanan Revathi
Published: March 2023

Spreading rumors on social media is a phenomenon that has destructive implication of societal interaction, diverts attention toward destructive behavior. The impact will be more influenced in healthcare management. This research aims to detect the rumors and identify the sources using deep learning algorithms. In our proposed system, after pre-processing, the tweet comments are extracted from topics and ranked as deny, support, query and comment. Then the comments are classified as positive, negative and neutral using Artificial Neural Network Neuro-fuzzy Inference System Spline-based pi-shaped Membership Function (ANISPIMF). Then the negative comments are classified into offensive, violence, misogyny and hate mongering by using Improved Deep Learning Neural Network (IDLNN) which is the combination of Deep Neural Network with Cuckoo Search–Flower Pollination Algorithm to optimize the weight values. The optimized ANISPIMF performs very well for the COVID-19 dataset in terms of Accuracy, Precision and Recall. The proposed system attains better performance and efficiency when weighted against prevailing methodologies — regarding the performance measures, there is an improvement of accuracy by 0.6%, recall by 0.7%, and precision by 1%, together with an [Formula: see text]1-score of 1.2% than the Multiloss Hierarchical Bi-LSTM with Attenuation Factor (MHA).
LIMEADE: From AI Explanations to Advice Taking
Authors: Lee Benjamin Charles Germain , Downey Doug , Lo Kyle , Weld Daniel S.
Published: March 2023

Research in human-centered AI has shown the benefits of systems that can explain their predictions. Methods that allow AI to take advice from humans in response to explanations are similarly useful. While both capabilities are well developed for
transparent
learning models (e.g., linear models and GA
2
Ms) and recent techniques (e.g., LIME and SHAP) can generate explanations for
opaque
models, little attention has been given to advice methods for opaque models. This article introduces LIMEADE, the first general framework that translates both positive and negative advice (expressed using high-level vocabulary such as that employed by post hoc explanations) into an update to an arbitrary, underlying opaque model. We demonstrate the generality of our approach with case studies on 70 real-world models across two broad domains: image classification and text recommendation. We show that our method improves accuracy compared to a rigorous baseline on the image classification domains. For the text modality, we apply our framework to a neural recommender system for scientific papers on a public website; our user study shows that our framework leads to significantly higher perceived user control, trust, and satisfaction.
A Survey on Machine Learning in Hardware Security
Authors: Köylü Troya Çağıl , Wedig Reinbrecht Cezar Rodolfo , Gebregiorgis Anteneh , Hamdioui Said , Taouil Mottaqiallah
Published: March 2023

Hardware security is currently a very influential domain, where each year countless works are published concerning attacks against hardware and countermeasures. A significant number of them use machine learning, which is proven to be very effective in other domains. This survey, as one of the early attempts, presents the usage of machine learning in hardware security in a full and organized manner. Our contributions include classification and introduction to the relevant fields of machine learning, a comprehensive and critical overview of machine learning usage in hardware security, and an investigation of the hardware attacks against machine learning (neural network) implementations.
Resource Management in Mobile Edge Computing: A Comprehensive Survey
Authors: Zhang Xiaojie , Debroy Saptarshi
Published: March 2023

With the evolution of 5G and Internet of Things technologies, Mobile Edge Computing (MEC) has emerged as a major computing paradigm. Compared to cloud computing, MEC integrates network control, computing, and storage to customizable, fast, reliable, and secure distributed services that are closer to the user and data site. Although a popular research topic, MEC resource management comes in many forms due to its emerging nature and there exists little consensus in the community. In this survey, we present a comprehensive review of existing research problems and relevant solutions within MEC resource management. We first describe the major problems in MEC resource allocation when the user applications have diverse performance requirements. We discuss the unique challenges caused by the dynamic nature of the environments and use cases where MEC is adopted. We also explore and categorize existing solutions that address such challenges. We particularly explore traditional optimization-based methods and deep learning-based approaches. In addition, we take a deeper dive into the most popular applications and use cases that adopt MEC paradigm and how MEC provides customized solutions for each use cases, in particular, video analytics applications. Finally, we outline the open research challenges and future directions.

1
Coffee as chemoprotectant in fatty liver disease: caffeine-dependent and caffeine-independent effects
Authors: Dranoff Jonathan A.
Published: March 2023

Coffee consumption is associated with a variety of positive health outcomes in patients with chronic liver disease, including decreased liver-related mortality. The evidence for this has come from a wide variety of epidemiological studies over the past decade and remains consistent. Because coffee contains a large number of constituent molecules, many of which vary based on coffee source, roasting approach, and preparation, it has been difficult to identify the mechanisms by which coffee improves liver-related health. The caffeine hypothesis suggests that the primary active ingredient in coffee in this context is caffeine, which is an antagonist of liver adenosine receptors. However, some lines of data suggest caffeine-independent effects as well. This review examines the biological plausibility for caffeine-independent effects in the context of a recent publication in this journal.
Mind-body connection: metabolite 4-ethylphenyl linked to anxiety behavior and oligodendrocyte modification in autism spectrum disorder
Authors: Pascual Francisco , Camilli Samuel , Lockey Richard F. , Kolliputi Narasaiah
Published: March 2023

The connection between byproducts of digestion in the gastrointestinal (GI) tract and neurocognitive disorders is an expanding area of research that has implications for autism spectrum disorder (ASD). Needham et al. (Needham et al. Nature 602: 647–653, 2022) revealed that mice with elevated levels of 4-ethylphenyl sulfate (4EPS), a GI tract-derived metabolite previously found at increased levels in the plasma of individuals with ASD, had altered brain activity, anxiety-influenced behavior, and reduced myelination of neuronal axons. This is a monumental step forward in the study of gut-derived neuroactive compounds, like 4EPS, and advances the understanding of their role in modulating behavior and brain activity in neurocognitive disorders.
Origins of pathological myofibroblasts in lung fibrosis: insights from lineage tracing mouse models in the single-cell RNA sequencing era
Authors: Homps-Legrand Méline , Crestani Bruno , Mailleux Arnaud A.
Published: March 2023

Idiopathic pulmonary fibrosis (IPF) is a rare interstitial lung disease with a poor prognosis. Chronic microinjuries, mainly caused by environmental factors to an aging alveolar epithelium, would lead to the aberrant differentiation and accumulation of aberrant mesenchymal cells with a contractile phenotype, known as fibrosis-associated myofibroblasts, which trigger abnormal extracellular matrix accumulation and fibrosis. The origin of those pathological myofibroblasts in pulmonary fibrosis is not fully understood to date. Lineage tracing methods using mouse models have opened new avenues for studying cell fate in a pathological context. This review aims to present a nonexhaustive list of different potential sources of those harmful myofibroblasts during lung fibrosis, based on these in vivo approaches, and considering the normal and fibrotic lung cellular atlas recently established by single-cell RNA sequencing.
The Influence of Glass Fiber/Glass Fiber Powder with β-Nucleating Agent on the Properties of Polypropylene
Authors: Yan Peng , Kang Shaoran , Ma Lebo
Published: March 2023

Glass fiber-reinforced polypropylene (PP/GF) has been widely used due to its high stiffness, but for some applications that need low-module characteristics, PP/GF will have limitations due to its lower toughness, so it is necessary to develop glass fiber-modified polypropylene with good stiffness–toughness balance performance. In this study, two average length glass fibers (4.5 mm and 12 mm) and glass fiber powder, combined with β-nucleating agent, were used to investigate the effects on the crystallization and mechanical properties of polypropylene. The results show that compared with glass fiber, glass fiber powder cooperates with β-nucleating agent reinforced polypropylene composite showed good stiffness–toughness balance performance, and β-crystals were found in the composite measured by Differential Scanning Calorimetry (DSC), the presence of β-crystals can improve the toughness of the composite.
Aviation Rivet Classification and Anomaly Detection Based on Deep Learning
Authors: Zhu Xiao-bo
Published: March 2023

The shortage of personnel and the high cost have become a major pain point in the current safety supervision work of the inspectors. Aiming at the problem that the aircraft maintenance inspector could not visit the scene in person during the epidemic, a remote safety supervision platform was built based on intelligent glasses and 5G network, and the real-time monitoring of the aircraft skin rivet status was realized. And a method of aviation rivet classification and anomaly detection based on deep learning algorithm was proposed. Firstly, according to the appearance of rivet head, the aviation rivet is classified, the data set of aviation rivet is made, and the aviation rivet classification and anomaly detection model are constructed. Evaluate the detection results from such indicators as confidence, precision, recall rate, and mAP and compare the algorithm with the detection results of Yolox-s, Yolox-m, Yolov5-s, Yolov5-m, and Yolov4. The results show that (1) the algorithm proposed in this paper can realize the classification of aviation rivets and the detection of abnormal conditions, the confidence of the detection results is more than 90%, and the average precision, recall, and AP value are above 95%, 85%, and 88%, respectively. (2) The order of rivet classification and abnormal detection effect from good to bad is Philips screws, round head rivets, flat head rivets, countersunk head rivets, blind rivets, and abnormal condition. (3) Compared with other algorithms, the aviation rivet classification abnormal target detection based on deep learning has absolute advantages in accuracy and speed.
An Economical Modification Method for MIL-101 to Capture Radioiodine Gaseous: Adsorption Properties and Enhancement Mechanism
Authors: Wang Peng , Qi Bing-Bing , Gu Ao-Tian , Chen Kai-Wei , Gong Chun-Hui , Yi Yang
Published: March 2023

Radioactive iodine is one of the inevitable by-products of nuclear energy application. However, it is a great threat to public health and the adsorbent needs to be adopted for removing the radioactive iodine. The iodine adsorbent needs to have some advantages, such as simple preparation method, low cost, high absorption capacity, and recyclable utilization. In order to meet the above requirements, the etched material of institute Lavoisier 101 (MIL-101) was prepared to absorb the gaseous iodine. After the MIL-101 is etched, the iodine adsorption performance has been greatly improved. The iodine adsorption experiment of etched MIL-101 with different etching time (1 h, 3 h, 4 h, and 6 h) was completed, the results show that the optimal etching time is 4 hours and the capture capacity of the etched MIL-101 is 371 wt%, which is about 22% higher than that of original MIL-101. The experiment results of XRD, FT-IR, and XPS prove that the components and structure of etched MIL-101 are accordable with those of MIL-101. The surface roughness is introduced in this work. The pore roughness is also an important factor to the adsorption capacity, and the related research also supports this conclusion. Furthermore, after iodine is absorbed, etched MIL-101 can be treated by ethanol for iodine release, and the etched MIL-101 has satisfied recyclability within three cycles. Compared with MIL-101, etched MIL-101 not only had good reversible adsorption of iodine but also can adsorb low-concentration iodine. The etched MIL-101 has a broad application prospect in nuclear emergency response and radiation detection.
Large Data Oriented to Image Information Fusion Spark and Improved Fruit Fly Optimization Based on the Density Clustering Algorithm
Authors: Zhang Yanfang
Published: March 2023

The density-based applied spatial clustering algorithm is an algorithm based on high-density interconnected regions, which discovers class clusters of arbitrary shapes in noisy data sets and is widely used. However, it suffers from slow computation speed due to large-scale disk I/O and clustering bias due to uneven density class clusters and poor parameter search ability. To address these problems, a parallel density clustering algorithm based on an improved fruit fly optimization algorithm and Spark memory iteration is proposed. The proposed algorithm first divides the data grid using an irregular dynamic density region partitioning strategy. Then, a hybrid fruit fly particle swarm algorithm based on a genetic optimization mechanism is proposed to achieve dynamic optimization seeking for parameters in local clustering to improve the clustering effect of local clustering. Finally, the local merging of samples in irregularly bounded grid cells under each partition is achieved by designing a custom clustering merging strategy. The experiments show that the improved algorithm is generally applicable to the clustering of different shape class clusters and larger scale data and has obvious improvement in accuracy and parallel efficiency.
Evaluation of the Potential of Duckweed as a Human Food, Bioethanol Production Feedstock, and Antileukaemia Drug
Authors: Guo Ling , Liu Jing , Wang Qingyan , Yang Yan , Yang You , Guo Qulian , Zhao Hai , Liu Wenjun
Published: March 2023

This study evaluated the potential of duckweed as a human food, ethanol feedstock, and anticancer drug. First, the nutritional value of wild duckweed was reported for the first time. Its main composition was similar to that of artificially cultivated duckweed, and thus, wild duckweed can serve as a great human food source. In addition, high-starch duckweed induced by nutrient starvation was fermented into bioethanol. A yield of 0.262 g/g, the highest duckweed-ethanol yield reported thus far, was achieved, indicating that duckweed is an excellent feedstock for ethanol production. Finally, the anticancer effects of duckweed flavonoids (DFs) were assessed for the first time using acute myeloid leukaemia (AML) cells as models in vitro and in vivo. The results revealed that DFs possessed antileukaemia activity and were safe and effective for AML therapy. In conclusion, duckweed was demonstrated to be helpful for humans for food security, energy crisis remediation, and tumour treatment.
Novel Study Antimicrobial and Biocompatibility Effect of Magnesium Silver Alloys 1% on Bovine Bacterial Species
Authors: Nomier Yousra , Meiβner Jessica , Kietzmann Manfred
Published: March 2023

MgAg 1% alloys inhibit bacterial growth during the dry‐off period. MgAg1% silver and magnesium amount was determined and the supernatant was used for the detection of antibacterial tests against S. aureus and E. coli and Geobacillus stearothermophilus var. calidolacits. The antibacterial effect of AgNO3 solution and degradation medium of MgAg1% sticks were evaluated. The bouillon dilution test showed a 5‐fold reduction in bacterial colonies. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) calculations were used to test the antibacterial activity. The Brilliant Black Reduction Test (BRT‐MRL screening test) showed inhibition of Geobacillus stearothermophilus bacteria at AgNO3 concentrations 0.01 mmol/l and 3 ml of degradation medium. Results were satisfying, concerning biocompatibility, degradation, and antibacterial effects.
A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

Purpose:

Accumulating analyses of pro-oncogenic molecular mechanisms triggered a rapid development of targeted cancer therapies. Although many of these treatments produce impressive initial responses, eventual resistance onset is practically unavoidable. One of the main approaches for preventing this refractory condition relies on the implementation of combination therapies. This includes dual-specificity reagents that affect both of their targets with a high level of selectivity. Unfortunately, selection of target combinations for these treatments is often confounded by limitations in our understanding of tumor biology. Here, we describe and validate a multipronged unbiased strategy for predicting optimal co-targets for bispecific therapeutics.

Experimental Design:

Our strategy integrates ex vivo genome-wide loss-of-function screening, BioID interactome profiling, and gene expression analysis of patient data to identify the best fit co-targets. Final validation of selected target combinations is done in tumorsphere cultures and xenograft models.

Results:

Integration of our experimental approaches unambiguously pointed toward EGFR and EPHA2 tyrosine kinase receptors as molecules of choice for co-targeting in multiple tumor types. Following this lead, we generated a human bispecific anti-EGFR/EPHA2 antibody that, as predicted, very effectively suppresses tumor growth compared with its prototype anti-EGFR therapeutic antibody, cetuximab.

Conclusions:

Our work not only presents a new bispecific antibody with a high potential for being developed into clinically relevant biologics, but more importantly, successfully validates a novel unbiased strategy for selecting biologically optimal target combinations. This is of a significant translational relevance, as such multifaceted unbiased approaches are likely to augment the development of effective combination therapies for cancer treatment.

See related commentary by Kumar, p. 2570
Recurrent Transient Asymptomatic Pulmonary Opacity with Long-Term Afatinib: A Case Report
Authors: Watanabe Keisuke , Kobayashi Nobuaki , Kaneko Takeshi
Published: March 2023

Afatinib is the second generation EGFR-TKI. Recently, transient asymptomatic pulmonary opacity (TAPO) was reported in EGFR-mutation harboring NSCLC receiving osimertinib. However, TAPO related to other EGFR-TKI has not been reported. Here, we reported a case of TAPO related to afatinib in lung adenocarcinoma harboring EGFR mutation. A 64-year-old male had the diagnosis of stage IV (The 7th edition of the staging system by the Union for International Cancer Control) lung adenocarcinoma harboring EGFR del 19 mutation. He received afatinib 40 mg per day from May 2015. Partial response was achieved, though the dose was reduced to 30 mg per day due to grade 3 rash. In January 2016, CT showed ground glass opacity in the right middle lobe, which resolved spontaneously 2 weeks later. He had no symptom and laboratory findings were not remarkable. Thereafter, recurrent GGO was revealed with chest CT, but all opacity improved without any medication (i.e., corticosteroids) or stopping afatinib. Therefore, we diagnosed a series of opacity as recurrent TAPO with afatinib. TAPO could occur with EGFR-TKI other than osimertinib. Further study is needed to establish the management of new opacity suggesting TAPO under EGFR-TKI treatment.
Current Surgical Concepts in Lynch Syndrome and Familial Adenomatous Polyposis
Authors: Horisberger Karoline , Mann Carolina , Lang Hauke
Published: March 2023

Background: Approximately 5% of colorectal cancers (CRCs) are associated with hereditary cancer syndromes. The natural history of these syndromes differs from sporadic cancers, and due to their increased risk of metachronous carcinomas, surgical approaches also differ. This review focuses on the current recommendations for surgical treatment and what evidence has led to these recommendations in the most clinically relevant hereditary CRC syndromes: Lynch syndrome (LS) and (attenuated) familial adenomatous polyposis (FAP). Summary: LS has no common phenotype and is caused by individual germline variants in one of the mismatch repair genes (MLH1, MSH2, MSH6, or PMS2). Because each gene is associated with a different risk of metachronous cancer, guidelines now differentiate between genes in their recommendations for oncology interventions. Classical and attenuated FAP are caused by germline mutations in the APC gene and have a characteristic phenotype. Although correlations exist between phenotype and genotype, the indication for surgery is predominantly based on clinical manifestation rather than specific gene mutations. Key Message: Currently, the recommendation on the two diseases tends to go in opposite directions: while some forms of FAP may require less extensive surgery, in some LS patients, more sophisticated knowledge of metachronous carcinoma risk leads to more extensive surgery.
Conceptual Change and Education: The Neglected Potential of Developmental Teaching Approaches
Authors: Gennen Thomas
Published: March 2023

Research on conceptual change (CC) has revealed that students face difficulties when learning that requires significant changes to their prior knowledge. Researchers have documented the challenges in education to promote CCs and concluded that conventional teaching does not facilitate these changes. However, while designing educational methods to address CC challenges is a central aim of CC research, it is an area of research that still requires refinement. I show that developmental teaching (DT) approaches, including El’konin-Davydov’s developmental education and Gal’perin’s method of stage-by-stage formation of mental actions and concepts, are promising for addressing CC challenges but are absent from CC research literature. I first review the CC challenges revealed in CC research, the way in which three CC research trends – framework theory, ontological theory, and knowledge-in-pieces theory – interpret them, and their educational recommendations to foster CC. Next, I present CC challenges and educational recommendations to foster CC from a DT perspective. I delineate convergences and divergences between the three CC research trends and DT research concerning both educational design and theories of CC. I conclude by suggesting articulations between DT research and CC research in general and the three CC research trends in particular.
Comparison of the Clinical Performance of Aptima HPV Assay and the Cobas 4800 Platform in Women with Normal Cytology and Positive High-Risk HPV
Authors: Kir Gozde , Dokmeci Guney Damla , Seneldir Hatice
Published: March 2023

Introduction: According to the current American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines, patients with normal cytology results may be referred for colposcopy according to their high-risk human papillomavirus (hrHPV) test results. A higher positive predictive value (PPV) of hrHPV has significance for preventing unnecessary colposcopic examinations. Several studies have compared the performance of the Aptima assay and the Cobas 4800 platform among patients who had minor cytologic abnormalities. However, in our English literature search, we found no other study that had been conducted to compare these two methods in patients with normal cytology. We thus aimed to compare the PPV of the Aptima assay and the Cobas 4800 platform among women with normal cytology. Methods: Between September 2017 and October 2022, we retrospectively identified 2,919 patients who had normal cytology and hrHPV positivity and had been referred for a colposcopy. Among them, 882 agreed to undergo a colposcopy; on examination, 134 had target lesions revealed and underwent a colposcopic punch biopsy. Results: Among the patients who underwent a colposcopic punch biopsy, 49 (38.9%) were tested with Aptima, and 77 (61.1%) were tested with Cobas. In the Aptima group, 29 (59.2%) patients showed benign histology, 2 (4.1%) patients had low-grade squamous intraepithelial lesions (LSILs), and 18 (36.7%) patients had ≥high-grade squamous intraepithelial lesions (HSILs) biopsy results. The false-positivity rate and PPV of Aptima were 63.3% (31/49) and 36.7% (95% confidence interval [CI]: 0.232–0.502), respectively, for a histopathologic diagnosis of ≥HSIL. In the Cobas group, 48 (62.3%) biopsies were benign, 11 (14.3%) reported an LSIL, and 18 (23.4%) biopsies were ≥HSIL. The false-positivity rate and PPV of Cobas were 76.6% (59/77) and 23.4% (95% CI: 0.139–0.328), respectively, concerning a ≥HSIL tissue diagnosis. The false-positivity rate of Aptima HPV 16 positivity was 40% (4/10). The false-positivity rate of Cobas HPV 16 positivity was 61.1% (11/18). The PPVs of HPV 16 positivity for Aptima and Cobas were 60% (95% CI: 0.296–0.903) and 38.9% (95% CI: 0.163–0.614), respectively, concerning ≥HSIL tissue diagnosis. Conclusion: We recommend analyzing the performances of hrHPV platforms in future, larger studies in patients with normal cytology rather than only in cases with abnormal cytology.
Early Impact of the COVID-19 Pandemic on Psycho-Oncological Support: A Latent Class Analysis
Authors: Schulze Jan Ben , Coker Penelope , von Känel Roland , Euler Sebastian , Günther Moritz Philipp
Published: March 2023

Introduction: Research suggests a global shortfall of psycho-oncological assessment and care during the COVID-19 pandemic in addition to delayed diagnosis of cancer. The present study is the first to explore the effect of the pandemic on the provision of psycho-oncological care, stage of cancer at first diagnosis, and duration of hospitalizations. Method: Retrospective latent class analysis of 4,639 electronic patient files with all types, treatment types, and stages of cancer, 370 of which were treated during the pandemic prior to availability of vaccinations. Discussion: Latent class analysis identified four subgroups based on differences in screening for distress, provision of psycho-oncological support (consultation with a psychiatrist or clinical psychologist), administration of psychotropic medication, use of 1:1 observation, stage of cancer at first diagnosis, and duration of hospitalizations. Yet, the pandemic had no effect on subgrouping. Thus, the COVID-19 pandemic had no effect on the provision of psycho-oncological support. Conclusion: Results are contrary to prior research. The efficiency and quality of procedures implemented to provide psycho-oncological support during and prior to the pandemic are critically reflected.
The Effect of a Multifaceted Intervention Including Classroom Education and Bariatric Weight Suit Use on Medical Students’ Attitudes toward Patients with Obesity
Authors: Renold Carlo , Deferm Nathalie Phyllis , Hauser Renward , Gerber Philipp , Bueter Marco , Thalheimer Andreas , Gero Daniel
Published: March 2023

Introduction: Weight bias refers to negative attitudes toward individuals because of their weight. Evidence-based strategies to successfully reduce weight bias in medical students are lacking. The purpose of this study was to investigate the impact of a multifaceted intervention on medical students’ attitudes toward patients with obesity. Methods: Third and fourth year medical students (n = 79), who enrolled in an 8-week graduate course focusing on the various epidemiologic, physiological, and clinical aspects of obesity, including a gamification task with bariatric weight suits (BWSs), were asked to complete the Nutrition, Exercise and Weight Management (NEW) Attitudes Scale questionnaire pre- and post-course. The inclusion period was between September 2018 and June 2021 and covered 4 consecutive groups of students. Results: The overall NEW Attitudes Scale scores did not change significantly pre- versus post-intervention (pre-course: 19.59, post-course: 24.21, p value = 0.24). However, the subgroup of 4th year medical students showed a significant improvement in their attitudes (pre-course: 16.4, post-course: 26.16, p value = 0.02). The Thurstone rating of 9 out of 31 individual survey items changed significantly from pre- to post-course with a moderate strength (Cramer’s V >0.2), including 5 items showing weight bias reduction. The disagreement with the statement “overweight/obese individuals lack willpower” increased from 37 to 68%. Conclusion: These findings suggest that in medical students with a low level of weight bias at baseline, a semester course on obesity combined with BWS use affects only a limited number of items of the NEW Attitudes Scale questionnaire. The sensitization of medical students to weight stigma has the potential to improve quality of healthcare for patients with obesity.
The Effects of 5 Years of Growth Hormone Treatment on Growth and Body Composition in Patients with Temple Syndrome
Authors: Juriaans Alicia F. , Trueba-Timmermans Demi J. , Kerkhof Gerthe F. , Grootjen Lionne N. , Walet Sylvia , Sas Theo C.J. , Rotteveel Joost , Zwaveling-Soonawala Nitash , Verrijn Stuart Annemarie A. , Hokken-Koelega Anita C.S.
Published: March 2023

Introduction: Temple syndrome (TS14) is a rare imprinting disorder caused by maternal uniparental disomy of chromosome 14, paternal deletion of 14q32.2, or an isolated methylation defect. Most patients with TS14 develop precocious puberty. Some patients with TS14 are treated with growth hormone (GH). However, evidence for the effectiveness of GH treatment in patients with TS14 is limited. Methods: This study describes the effect of GH treatment in 13 children and provides a subgroup analysis of 5 prepubertal children with TS14. We studied height, weight, body composition by dual-energy X-ray absorptiometry, resting energy expenditure (REE), and laboratory parameters during 5 years of GH treatment. Results: In the entire group, mean (95% CI) height SDS increased significantly during 5 years of GH treatment from −1.78 (−2.52; −1.04) to 0.11 (−0.66; 0.87). Fat mass percentage SDS decreased significantly during the first year of GH, and lean body mass (LBM) SDS and LBM index increased significantly during 5 years of treatment. IGF-1 and IGF-BP3 levels rose rapidly during GH treatment, and the IGF-1/IGF-BP3 molar ratio remained relatively low. Thyroid hormone levels, fasting serum glucose, and insulin levels remained normal. In the prepubertal group, median (interquartile range [IQR]) height SDS, LBM SDS, and LBM index also increased. REE was normal at start and did not change during 1 year of treatment. Five patients reached adult height and their median (IQR) height SDS was 0.67 (−1.83; −0.01). Conclusion: GH treatment in patients with TS14 normalizes height SDS and improves body composition. There were no adverse effects or safety concerns during GH treatment.
Notas sobre opiliões
Authors: Soares B. M.
Published: March 2023

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Um novo gênero e espécie de acanthocininae. (Col. Lamiidae)
Authors: Lane Frederico
Published: March 2023

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Nova contribuição à ornitologia do reconcavo (baia)
Authors: Pinto Oliverio
Published: March 2023

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Impaired Maternal‐Fetal Environment and Risk for Preoperative Focal White Matter Injury in Neonates With Complex Congenital Heart Disease
Authors: Licht Daniel J. , Jacobwitz Marin , Lynch Jennifer M. , Ko Tiffany , Boorady Timothy , Devarajan Mahima , Heye Kristina N. , Mensah‐Brown Kobina , Newland John J. , Schmidt Alexander , Schwab Peter , Winters Madeline , Nicolson Susan C. , Montenegro Lisa M. , Fuller Stephanie , Mascio Christopher , Gaynor J. William , Yodh Arjun G. , Gebb Juliana , Vossough Arastoo , Choi Grace H. , Putt Mary E.
Published: March 2023

Background

Infants with congenital heart disease (CHD) are at risk for white matter injury (WMI) before neonatal heart surgery. Better knowledge of the causes of preoperative WMI may provide insights into interventions that improve neurodevelopmental outcomes in these patients.

Methods and Results

A prospective single‐center study of preoperative WMI in neonates with CHD recorded data on primary cardiac diagnosis, maternal‐fetal environment (MFE), delivery type, subject anthropometrics, and preoperative care. Total maturation score and WMI were assessed, and stepwise logistic regression modeling selected risk factors for WMI. Among subjects with severe CHD (n=183) who received a preoperative brain magnetic resonance imaging, WMI occurred in 40 (21.9%) patients. WMI prevalence (21.4%–22.1%) and mean volumes (119.7–160.4 mm
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) were similar across CHD diagnoses. Stepwise logistic regression selected impaired MFE (odds ratio [OR], 2.85 [95% CI, 1.29–6.30]), male sex (OR, 2.27 [95% CI, 1.03–5.36]), and older age at surgery/magnetic resonance imaging (OR, 1.20 per day [95% CI, 1.03–1.41]) as risk factors for preoperative WMI and higher total maturation score values (OR, 0.65 per unit increase [95% CI, 0.43–0.95]) as protective. A quarter (24.6%; n=45) of subjects had ≥1 components of impaired MFE (gestational diabetes [n=12; 6.6%], gestational hypertension [n=11; 6.0%], preeclampsia [n=2; 1.1%], tobacco use [n=9; 4.9%], hypothyroidism [n=6; 3.3%], and other [n=16; 8.7%]). In a subset of 138 subjects, an exploratory analysis of additional MFE‐related factors disclosed other potential risk factors for WMI.

Conclusions

This study is the first to identify impaired MFE as an important risk factor for preoperative WMI. Vulnerability to preoperative WMI was shared across CHD diagnoses.