bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Magnetic Field on Insecticide Toxicity Measured by Biological and Biochemical Parameters of Earias insulana (Boisd)
Authors: El‐Bassouiny Hisham M. , El‐Medany Warda A. Z. , Kandil Mervat A. A.
Published: August 2022

This study illustrates the effect of magnetic field (MF) on the toxicity of two insecticides, emamectin benzoate (Emazoate 2.15% EC) and spinosad (SpinTor 24% SC), and determines their adverse effects on the bollworm (Earias insulana) through various biological and biochemical assays. The investigation indicated that exposure to the insecticides in a MF of 180 mT resulted in stronger toxicity, with LC50 values of 0.162, 1.211, and 1.770 ppm, respectively. In addition, the results showed that magnetized insecticides significantly increased in the duration of the total immature stages (larvae and/or pupae) 32.1 and 36.6 days, compared with 27.9 and 30.5 days, respectively, in the nonmagnetized insecticides, while untreated check was 21 days. Also, the magnetized insecticides reduced the percentage of adult emergence, and increased deformations in the larval and pupal stages. Furthermore, sex ratio was greatly affected by exposure to both insecticides in conjunction with the MF. Exposure of the larvae of E insulana to magnetized insecticides can bring about malfunction in some biochemical process and significantly decreased the invertase activity, and decreased the total protein and carbohydrates. In contrast, it can increase amylase compared with nonmagnetized insecticides and untreated controls. Results concluded that the two insecticides’ MF affected growth, survival time, and biological and biochemical parameters of E. insulana. © 2022 Bioelectromagnetics Society.
New transcriptome and clinical findings of platelet‐activating factor in chronic spontaneous urticaria: Pathogenic and treatment relevance
Authors: Andrades Evelyn , Clarós Miquel , Torres Juan Vicente , Nonell Lara , González Mónica , Curto‐Barredo Laia , Rozas‐Muñoz Eduardo , Gimeno Ramon , Barranco Carlos , Pujol Ramon M. , Izquierdo Iñaki , Giménez‐Arnau Ana M.
Published: August 2022

The objective of the study was to assess the pathogenic and treatment relevance of Platelet Activating factor (PAF) in chronic spontaneous urticaria (CSU). The expression and cellular location of PAF receptor (PAFR) and serum levels of PAF and PAF acetylhydrolase (PAF‐AH) in patients with moderate/severe CSU (n = 45) and healthy controls (HCs, n = 17) were studied. Skin samples from the active wheal (LS‐CSU, 13 samples for qPCR and 33 for immunohistochemistry) and non‐lesional skin (NLS‐CSU, 13 samples) of CSU patients and HCs (13 samples and 5 for immunohistochemistry) were analyzed. Serum PAF and PAF‐AH levels were measured by ELISA and compared between HC (10 samples) and CSU patients (25 samples) and, among them, between those refractory and non‐refractory to second‐generation H1‐antihistamines (sgAH). PAFR mRNA expression was significantly higher in LS‐CSU versus HCs (p = 0.014). PAFR positive staining in immunohistochemistry was mainly found in the epidermal basal layer in HCs, whereas it was broadly present along the epidermis in LS‐CSU samples. Endothelial cells showed PAFR expression exclusively in LS‐CSU and NLS‐CSU samples. PAFR expression was observed in the nerves of HC, LS‐CSU, and NLS‐CSU samples. Double PAFR/CD43 expression showed that T‐lymphocytes were the main cell type from the wheal inflammatory infiltrate expressing PAFR. A significantly lower PAF‐AH/PAF ratio was observed in sgAH non‐responders versus responders (6.1 vs. 12.6; p = 0.049). Our study confirms that PAF is a mediator of wheal pathogenesis in CSU. The significantly lower PAF‐AH/PAF ratio in sgAH non‐responders vs responders suggests that PAF could be a potential biomarker of sgAH refractoriness.
Highly Luminescent Positively Charged Quantum Dots Interacting with Proteins and Cells†
Authors: Wang Haixia , Nienhaus Karin , Shang Li , Nienhaus Gerd Ulrich
Published: August 2022

Comprehensive Summary

We have studied interactions between positively charged MUTAB‐stabilized quantum dots (QDs) and model proteins, serum and live cells using fluorescence correlation spectroscopy (FCS), dynamic light scattering (DLS), time‐resolved photoluminescence (PL) and live‐cell fluorescence imaging. Using human serum albumin (HSA) as a model protein, we measured the growth of a protein adsorption layer (“protein corona”) via time‐resolved FCS. Corona formation was characterized by an apparent equilibrium dissociation coefficient, KD ≈ 10 μM. HSA adlayer growth was surprisingly slow (timescale ca. 30 min), in stark contrast to many similar measurements with HSA and other proteins and different NPs. Time‐resolved PL data revealed a characteristic quenching behavior depending on the QD surface coverage with HSA. Taken together, we found that MUTAB‐QDs initially bind HSA molecules weakly (KD ≈ 700 μM); however, the affinity is enhanced over time, presumably due to proton injection into the MUTAB layer by HSA triggering ligand dissociation. This process was also observed with human blood serum, showing equal kinetics for comparable HSA concentration. Moreover, imaging experiments with cultured human cells (HeLa) revealed that MUTAB‐QDs bind to the cell membrane and perforate it. This process is reduced upon pre‐adsorption of proteins on the MUTAB‐QD surfaces.
A color channel multiplexing approach for robust discrete wavelet transform based image watermarking
Authors: Saritas Omer Faruk , Ozturk Serkan
Published: August 2022

Copyright protection of digital images has become a consequential issue in recent years. To prevent a breach of copyright for a color image, this article presents a novel discrete wavelet transform (DWT) based robust image watermarking method with a color channel multiplexing approach. In this proposed method, the original color image is separated into red, green, and blue color channels. One of these color channels is copied and a set of four channels is obtained. Then these channels are combined to obtain a new gray‐level cover image. 2‐level DWT is performed on the cover image. Arnold scrambled binary watermark image i embedded into the low‐frequency sub‐band of the cover image. 2‐level inverse DWT is performed to produce a gray‐level watermarked image. Then a demultiplexing process is performed by separating the gray‐level watermarked image into four color channels. The average values of the two copied color channels are calculated and then converted into a single‐color channel. Finally, the watermarked color image is get by merging three different color channels. To approve the performance of the presented method, various experimental tests have been performed and a benchmarking analysis has been conducted. The results show that the proposed method is robust against non‐linear and linear attacks while protecting watermarking imperceptibility.
Enabling efficient rate and temporal coding using reliability‐aware design of a neuromorphic circuit
Authors: Picardo Siona Menezes , Shaik Jani Babu , Singhal Sonal , Goel Nilesh
Published: August 2022

Reliability aspects such as bias temperature instability (BTI) and hot carrier injection (HCI) affecting devices in advanced CMOS‐based technology have been the subject of active research in recent decades. Due to these reliability issues, various digital and analog circuits were investigated for degradation. However, circuit blocks like the neuron circuits of neuromorphic systems are not fully explored. This work is inclined toward examining the collective degradation impact of BTI and HCI due to aging in an adaptive exponential “integrate and fire” (I&F) model‐based, neuromorphic neuron circuit. Detailed degradation analysis of the stimulated neuron circuit aided in identifying possible mismatches/faults associated with neuron spikes. These factors could reduce the efficiency of the neuronal circuit by potentially affecting the transmission of information in a neuromorphic system. Various performance parameters were then derived to quantify the extent of circuit deterioration. The proposed reliability‐aware design aims to improve the circuit degradation through its effectiveness in alleviating the overall reliability impact. It demonstrates enhanced circuit operation in spike generation even after aging. The circuit performance is validated through simulations at “Time0” (pre‐degradation) and “Aged” (post‐degradation) neuron netlists, which is then compared with the proposed reliability‐aware circuit.
Efficacy of gel immersion endoscopic ultrasonography for delineating the duodenal papilla and pancreatobiliary ducts: A retrospective study with video
Authors: Toyonaga Haruka , Kin Toshifumi , Iwano Kosuke , Nakamura Risa , Shimizu Takao , Chikugo Koki , Ishii Tatsuya , Nasuno Hiroshi , Hayashi Tsuyoshi , Takahashi Kuniyuki , Yamazaki Hajime , Katanuma Akio
Published: August 2022

Objectives

Endoscopic ultrasonography is an important examination for periampullary diseases. The duodenum is filled with water to ensure a clear image and distend the duodenal wall without burying the papilla within duodenal folds; however, peristalsis frequently makes it difficult to maintain water within the duodenum. The gel immersion method (intestine is filled with viscosity gel) has recently been attracting attention. We evaluated the usefulness of using this method for endoscopic ultrasonography to detect and delineate the major duodenal papilla.

Methods

Fifty‐nine consecutive patients who underwent gel immersion‐endoscopic ultrasonography between February and March 2021 were included retrospectively. The papilla was observed by filling the duodenum with clear viscosity gel. Outcomes were the rate of duodenal distention, delineation rates of the papilla, the time required for delineation, volume of the gel used, and adverse events.

Results

Duodenal distention was excellent, good, and poor in 58%, 34%, and 7% of cases, respectively. The delineation rates of the papilla in the axial and longitudinal views were 98% and 66%, respectively. The median time required to delineate the papilla in each view was 3.1 (range, 1.0–1.4) and 7.9 (1.9–28.6) min; the median volume of the gel used was 80 (30–150) ml and 100 (50–200) ml, respectively. No adverse events were noted.

Conclusions

Gel immersion‐endoscopic ultrasonography provided sufficient duodenal distention, leading to high rates of detection and delineation of the papilla using a small volume of gel within a short time. This method may be useful for the evaluation of the ampullary region.
The role ofE. maritimum(L.) in the dune pollination network of the Balearic Islands
Authors: Cortés‐Fernández Iván , Cerrato Marcello Dante , Ribas‐Serra Arnau , Ferrà Xavier Canyelles , Gil‐Vives Lorenzo
Published: August 2022

Eryngium maritimumL. (Apiaceae) is a geophyte that inhabits in the dunes of the Mediterranean and Atlantic. Although it is a highly entomophilous species, there is little literature on its pollinator assemblage. The aim of this study is to analyze the role played byE. maritimumin the dune pollination network of the Balearic Islands, where there is an intense anthropogenic impact in its habitat. For this purpose, two populations located in the North and South of Mallorca were chosen, in which diurnal transects were carried out to observe and capture pollinators on 15 plant species during the anthesis period ofE. maritimum. The flowering period of 10 plant species flowering at the same period thanE. maritimumwas analyzed to identify periods of competition. A total of 71 pollinator species were found, belonging to 30 different families.Eryngium maritimumis a strongly generalist species, with a total of 45 pollinator species. Two new species,Odice blandulaandLeucospis gigas, were found for the first time in Mallorca. In terms of pollinators,Teucrium dunenseandHelichrysum stoechasare the most similar species toE. maritimum. However, analysis of phenology suggests that these three species have been able to decouple their blooms to avoid competition. The present study shows thatE. maritimumplays an important role in the dune pollination network, being its anthesis located at the end of the dune flowering season, when there are no functionally similar species in flower.
Computerized classification method for histological classification of masses on breast ultrasonographic images using convolutional neural networks with ROI pooling
Authors: Hizukuri Akiyoshi , Kunieda Shinya , Nakayama Ryohei
Published: August 2022

It can be difficult for clinicians to correctly determine histological classifications of masses on breast ultrasonographic images. The purpose of this study was to develop a computerized classification method for histological classification of masses on breast ultrasonographic images using convolutional neural networks (CNN) with a ROI pooling that analyzes feature maps focusing on the mass region. Our dataset consisted of 585 breast ultrasonographic images obtained from 585 patients. It included 288 malignant masses (218 invasive and 70 noninvasive carcinomas) and 297 benign masses (115 cysts and 182 fibroadenomas). In this study, we developed a modified CNN model based on ResNet‐18, in which the ROI pooling and two fully connected layers with a softmax function were introduced after the second and fourth residual block on ResNet‐18, respectively. The proposed CNN model was employed to distinguish among four different types of histological classifications for masses. A three‐fold cross validation method was used for training and testing the proposed CNN model. The average accuracy, sensitivity, specificity, positive predictive value and negative predictive value for the proposed CNN model were 81.7%, 91.0%, 91.2%, 91.0%, and 91.2%, respectively. Those results were substantially greater than those with ResNet‐18 (70.3%, 83.0%, 87.2%, 86.3%, and 84.1%).
Impact of theCOVID‐19 pandemic on people with epilepsy: Findings from theUSarm of theCOV‐Estudy
Authors: Dugan Patricia , Carroll Elizabeth , Thorpe Jennifer , Jette Nathalie , Agarwal Parul , Ashby Samantha , Hanna Jane , French Jacqueline , Devinsky Orrin , Sen Arjune ,   the COVID‐19 Epilepsy COV‐E Study Group
Published: August 2022

Objectives

As part of the COVID‐19 and Epilepsy (COV‐E) global study, we aimed to understand the impact of COVID‐19 on the medical care and well‐being of people with epilepsy (PWE) in the United States, based on their perspectives and those of their caregivers.

Methods

Separate surveys designed for PWE and their caregivers were circulated from April 2020 to July 2021; modifications in March 2021 included a question about COVID‐19 vaccination status.

Results

We received 788 responses, 71% from PWE (n = 559) and 29% (n = 229) from caregivers of persons with epilepsy. A third (n = 308) of respondents reported a change in their health or in the health of the person they care for. Twenty‐seven percent (n = 210) reported issues related to worsening mental health. Of respondents taking ASMs (n = 769), 10% (n = 78) reported difficulty taking medications on time, mostly due to stress causing forgetfulness. Less than half of respondents received counseling on mental health and stress. Less than half of the PWE reported having discussions with their healthcare providers about sleep, ASMs, and potential side effects, while a larger proportion of caregivers (81%) reported having had discussions with their healthcare providers on the same topics. More PWE and caregivers reported that COVID‐19‐related measures caused adverse impact on their health in the post‐vaccine period than during the pre‐vaccine period, citing mental health issues as the primary reason.

Significance

Our findings indicate that the impact of the COVID‐19 pandemic in the US on PWE is multifaceted. Apart from the increased risk of poor COVID‐19 outcomes, the pandemic has also had negative effects on mental health and self‐management. Healthcare providers must be vigilant for increased emotional distress in PWE during the pandemic and consider the importance of effective counseling to diminish risks related to exacerbated treatment gaps.
Reduzierung von Versinterung durch optimierte Drainagebedingungen – Erkenntnisse eines Feldversuchs
Authors: Boch Ronny , Pilgerstorfer Thomas , Moritz Bernd
Published: August 2022

A field test was carried out in Koralmtunnel in order to enhance process understanding and to optimize the drainage system in a tunnel section that is complex in terms of hydrochemistry, water inflow and mineral (calcareous scale, iron ochre) and biological (microbial mats) deposits. The field test comprised three test fields with different system components and flow characteristics. The development of critical waters and deposits was recorded by continuous measurements of relevant water and air parameters by means of autonomous sensors/data loggers. Furthermore, the components were ”forensically“ examined with respect to scale formation. The experiments show the crucial importance of gas exchange (CO2, oxygen ingress), filling level (flow geometry/regime), residence time of waters and water‐air interaction in the drainage system. The type, material consistency, and amount of scale and biofilms depend significantly on specific gradients. Floating scale crusts formed in stagnant sections, biofilms and iron ochre deposits of soft consistency formed at higher flow rates. Seepage packs and siphons turned out to be potential sediment traps with decreasing flow‐through with no access. Drainage hoses and dimpled membranes tend to be beneficial because they can prevent air exchange at relatively high flow rates. High CO2 partial pressure within these components (measured and modeled) inhibits carbonate precipitation. The drainage system is locally designed as a series of direct cross‐drains with simple flow paths, restricted air exchange, precautionary cleaning access, and optional water hardness stabilization (liquid conditioning).
Dokumentation von Versinterungen im Koralmtunnel – Kartierung und Beprobung in der Praxis
Authors: Pointner Peter , Sellner Sabine
Published: August 2022

The bidding consortium 3G Gruppe Geotechnik Graz ZT GmbH and Pöyry Infra GmbH as well as Geoconsult ZT GmbH and BGG Consult Dr. Peter Waibel ZT‐GmbH were awarded the contract for the geological and hydrogeological documentation during the construction of the 33 km long Koralm Tunnel, which was split into three lots. To assess the potential for scale deposition, ongoing documentation and surveys of the groundwater inflows were undertaken in addition to the usual hydrogeological documentation. The scope of documentation included mapping of scale deposition and groundwater inflows, regular site visits and sampling of water and solids in the excavated tunnel (shotcrete and segmental lining) both during and after excavation works. Furthermore, long‐term monitoring of the water inflows (on‐site parameters, determination of / changes in humidity) and laboratory analysis of the individual and mixed groundwater samples identified the parameters required to assess the potential for scale deposition. The documentation, analysis and assessments provided the basis for ultimately deciding which tunnel sections would require hardness stabilisation measures to reduce or inhibit scaling and calcium carbonate precipitations in the drainage system during the operational phase.
Charakterisierung von mikrobiellen Biofilmen aus Tunnelwässern
Authors: Koraimann Günther , Bischof Karin
Published: August 2022

Microorganisms mainly from the domain of bacteria dominate life in the terrestrial subsurface up to a depth of several kilometers. Microbial life in that habitat is dependent on the availability of water and nutrients of biotic or abiotic origin. To produce biomass, bacterial primary producers are capable to use simple building blocks such as CO2, H2, CH4, reduced iron and sulfur, nitrate, phosphate as well as other salts and trace elements. Here, we describe the microbial content of several biofilm samples taken during the construction phase of a railway tunnel between the provinces of Styria and Carinthia (Koralm Tunnel). We could identify bacterial cells using light microscopy and used 16S rDNA based microbial profiling to characterize the bacterial community structure. Our results clearly show that the massive biofilms in tunnel drainage water were produced by a bacterial consortium typical for the deep continental subsurface biosphere. In many cases the majority of the consortium could be assigned to autotrophs, methanotrophs and methylotrophs.
The unintended consequences of hospital strikes on patient outcomes evidence from multiple strikes in the Portuguese National Health Service
Authors: Costa Eduardo
Published: August 2022

Hospital strikes in the Portuguese National Health Service (NHS) are becoming increasingly frequent. This paper analyses the effect of different health professionals' strikes (physicians, nurses, and diagnostic and therapeutic technicians (DTT) ‐ DTT) on patient outcomes and hospital activity. Patient‐level data, comprising all NHS hospital admissions in mainland Portugal from 2012 to 2018, is used together with a comprehensive strike dataset with almost 130 protests. Data suggests that hospital operations are partially disrupted during strikes, with sharp reductions in surgical admissions (up to 54%) and a decline on both inpatient and outpatient care admissions. The model controls for hospital characteristics, time and regional fixed effects, and case‐mix changes. Results suggest a modest increase in hospital mortality limited for patients admitted during physicians' strikes, and a slight reduction in mortality for patients already at the hospital when a strike takes place. Increases in readmission rates and length of stay are also found. Results suggest that hospitals and legal minimum staffing levels defined during strikes are not flexible enough to accommodate sudden disruptions in staffing, regardless of hospital quality in periods without strikes.
Evaluation of nitrogen mineralization under various irrigation water qualities and nitrogen application rates for mulched drip irrigation in an arid region
Authors: Ma Chao , Wang Jun , Li Jiusheng
Published: August 2022

Understanding the interactive effects of irrigation water quality and fertilization on nitrogen mineralization (Nmin) and accurately predicting Nmin are of great importance for the secure and efficient utilization of brackish water in arid regions. A pot experiment was conducted to determine the Nmin under different drip irrigation water salinities and nitrogen application rates and to modify the nitrogen mineralization potential (N0) and mineralization rate constants (k) of the first‐order kinetic equation of Nmin. An in situ field experiment was conducted to validate the modified equation. The results showed that the amounts of Nmin for water salinities of 1.27, 3.03, and 4.90 g L−1 were 58.9, 76.1, and 45.4 kg ha−1, respectively. Nmin was stimulated when the soil salinities were lower than 6.6, 6.1 and 3.9 g kg−1 for nitrogen application rates of 255, 315 and 375 kg ha−1, respectively. Nitrogen application significantly reduced Nmin. When the nitrogen application rate increased to 375 kg ha−1, the net Nmin rate remained lower, and the effects of salinity on Nmin were attenuated. The Nmin model with modified N0 and k values was developed considering the impacts of soil organic nitrogen, nitrogen application rate, and soil salinity. Model testing indicated that the modified model provided an acceptable estimation of Nmin under field conditions. It will be helpful for developing rational fertilization strategies of drip irrigation with brackish water in arid regions.
Characterization of microparticles derived from waste plastics and their bio‐interaction with human lung A549 cells
Authors: Bengalli Rossella , Zerboni Alessandra , Bonfanti Patrizia , Saibene Melissa , Mehn Dora , Cella Claudia , Ponti Jessica , La Spina Rita , Mantecca Paride
Published: August 2022

Microplastics (MPs) represent a worldwide emerging relevant concern toward human and environmental health due to their intentional or unintentional release. Human exposure to MPs by inhalation is predicted to be among the most hazardous. MPs include both engineered, or primary MPs, and secondary MPs, materials obtained by fragmentation from any plastic good. The major part of the environmental MPs is constituted by the second ones that are irregular in size, shape and composition. These features make the study of the biological impact of heterogenous MPs of extremely high relevance to better estimate the real toxicological hazards of these materials on human and environmental organisms. The smallest fractions of plastic granules, relying on the micron‐sized scale, can be considered as the most abundant component of the environmental MPs, and for this reason, they are typically used to perform toxicity tests using in vitro systems representative of an inhalation exposure scenario. In the present work, MPs obtained from industrial treatment of waste plastics (wMPs < 50 μm) were investigated, and after the physico‐chemical characterization, the cytotoxic, inflammatory and genotoxic responses, as well as the modality of wMPs interactions with alveolar lung cells, were determined. Obtained results indicated that, at high concentrations (100 μg/ml) and prolonged exposure time (48 h), wMPs affect biological responses by inducing inflammation and genotoxicity, as a result of the cell–wMP interactions, also including the uptake of the smaller particles.
Monitoring stimulus‐evoked hemodynamic response during deep brain stimulation with single fiber spectroscopy
Authors: Yu Linhui , Noor M. Sohail , Kiss Zelma H. T. , Murari Kartikeya
Published: August 2022

Deep brain stimulation (DBS) is a revolutionary treatment for movement disorders. Measuring DBS‐induced hemodynamic responses may be useful for surgical guidance of DBS electrode implantation as well as to study the mechanism and assess therapeutic effects of DBS. In this study, we evaluated the performance of a single fiber spectroscopic (SFS) system for measuring hemodynamic response in different cortical layers in a DBS animal model. We showed that SFS is capable of measuring minute relative changes in oxygen saturation and blood volume fraction in‐vivo at a sampling rate of 22–33 Hz. During stimulation, blood volume fraction increased, while oxygen saturation showed both increases and decreases at different cortical depths across animals. In addition, we showed the potential of using SFS for measuring other physiological parameters, for example, heart rate, and respiratory rate.
ppdx: Automated modeling of protein–protein interaction descriptors for use with machine learning
Authors: Conti Simone , Ovchinnikov Victor , Karplus Martin
Published: August 2022

This paper describes ppdx, a python workflow tool that combines protein sequence alignment, homology modeling, and structural refinement, to compute a broad array of descriptors for characterizing protein–protein interactions. The descriptors can be used to predict various properties of interest, such as protein–protein binding affinities, or inhibitory concentrations (IC50), using approaches that range from simple regression to more complex machine learning models. The software is highly modular. It supports different protocols for generating structures, and 95 descriptors can be currently computed. More protocols and descriptors can be easily added. The implementation is highly parallel and can fully exploit the available cores in a single workstation, or multiple nodes on a supercomputer, allowing many systems to be analyzed simultaneously. As an illustrative application, ppdx is used to parametrize a model that predicts the IC50 of a set of antigens and a class of antibodies directed to the influenza hemagglutinin stalk.
Silencing LINC00665 inhibits cutaneous melanoma in vitro progression and induces apoptosis via the miR‐339‐3p/TUBB
Authors: Liu Yi , Ma Shanshan , Ma Qichao , Zhu Haigang
Published: August 2022

Background

LncRNAs are closely related to cutaneous melanoma (CM) tumorigenesis and metastasis, and it can affect the progression of CM by regulating cell proliferation, migration, invasion, apoptosis, and other cellular mechanisms. This study investigated the role of LINC00665 in CM.

Methods

Expressions of LINC00665, miR‐339‐3p, and tubulin beta chain (TUBB) in CM cells were analyzed by qRT‐PCR and/or Western blot. The LINC00665/miR‐339‐3p/TUBB targeting network was predicted by bioinformatics tools, screened out by Venn diagrams and analyzed by Pearson's correlation coefficients, followed by validation via dual‐luciferase reporter assay and/or pull‐down assay. Transfection of siLINC00665 or miR‐339‐3p inhibitor/mimic was conducted with CM cells whose viability, proliferation, migration, invasion, cell cycle progression, and apoptosis were measured by CCK‐8 assay, colony formation assay, wound healing assay, Transwell assay, and flow cytometry. The associations of TUBB with tumor biological characteristics and other proteins were analyzed by CanserSEA and String, respectively.

Results

High‐expressed LINC00665 was detected in CM cells. Silencing LINC00665 decreased CM cell viability; inhibited colony formation, cell cycle progression, migration and invasion; enhanced apoptosis; and upregulated miR‐339‐3p. LINC00665 targeted miR‐339‐3p which targeted TUBB. MiR‐339‐3p upregulation induced effects similar to the LINC00665‐silencing‐induced effects and could downregulate TUBB, which was associated with malignant behaviors and related to other five proteins. MiR‐339‐3p downregulation induced the opposite effects of what miR‐339‐3p upregulation induced, and the miR‐339‐3p downregulation‐induced effects could be reversed by LINC00665 silencing.

Conclusion

Silencing LINC00665 inhibits in vitro CM progression and induces apoptosis via the miR‐339‐3p/TUBB axis.
The postpartum uterine ultrasonographic scale in assessment of uterine involution after cesarean section in treated thrombophilia pregnant patients at term
Authors: Filip Catalina , Covali Roxana , Socolov Demetra , Carauleanu Alexandru , Tanasa Ingrid Andrada , Scripcariu Ioana Sadyie , Ciuhodaru Madalina , Butureanu Tudor , Pavaleanu Ioana , Akad Mona , Boiculese Lucian Vasile , Socolov Razvan
Published: August 2022

Background

Pregnancy is a prothrombotic condition which can be abnormally exaggerated in women with thrombophilia.

Methods

In a prospective study, patients who delivered at term, by cesarean section, between 1 October 2017 and 1 December 2021, who already had a diagnosis of thrombophilia before coming to our hospital, were included in the study group (n = 80). A similar number of nonthrombophilia patients (n = 80) without any history of thrombotic events, age‐ and para‐matched with the study group, were included in the control group. The postpartum uterine ultrasonographic scale (PUUS) values, in the first 24–48 h, were correlated with the patients' data.

Results

The P‐LCR (platelet large cell ratio), was significantly higher in the treated thrombophilia group (p = 0.042). There was no correlation between PUUS and complete blood count values, coagulation factors, maternal characteristics, or fetal outcomes, except for postpartum neutrophils (p = 0.047) and postpartum platelet count (p = 0.046).

Conclusions

Postpartum uterine involution was not significantly different, after cesarean section, between treated thrombophilia patients and nonthrombophilia patients. Involution correlated only with postpartum neutrophils and postpartum platelet count.
Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles
Authors: Xiong Xiao , Ke Xiurong , Wang Lu , Lin Yusheng , Wang Shuhong , Yao Zhimeng , Li Kai , Luo Yichen , Liu Fan , Pan Yunlong , Yeung Sai‐Ching J. , Helfrich Wijnand , Zhang Hao
Published: August 2022

Cancer vaccines critically rely on the availability of targetable immunogenic cancer‐specific neoepitopes. However, mutation‐based immunogenic neoantigens are rare or even non‐existent in subgroups of cancer types. To address this issue, we exploited a cancer‐specific aberrant transcription‐induced chimeric RNA, designated A‐PaschiRNA, as a possible source of clinically relevant and targetable neoantigens. A‐PaschiRNA encodes a recently discovered cancer‐specific chimeric protein that comprises full‐length astrotactin‐2 (ASTN2) C‐terminally fused in‐frame to the antisense sequence of the 18th intron of pregnancy‐associated plasma protein‐A (PAPPA). We used extracellular vesicles (EVs) from A‐PaschiRNA‐transfected dendritic cells (DCs) to produce the cell‐free anticancer vaccine DEXA‐P. Treatment of immunocompetent cancer‐bearing mice with DEXA‐P inhibited tumour growth and prolonged animal survival. In summary, we demonstrate for the first time that cancer‐specific transcription‐induced chimeric RNAs can be exploited to produce a cell‐free cancer vaccine that induces potent CD8+ T cell‐mediated anticancer immunity. Our novel approach may be particularly useful for developing cancer vaccines to treat malignancies with low mutational burden or without mutation‐based antigens. Moreover, this cell‐free anticancer vaccine approach may offer several practical advantages over cell‐based vaccines, such as ease of scalability and genetic modifiability as well as enhanced shelf life.
The goldilocks conundrum: Disclosing discrimination risks in informed consent
Authors: Prince Anya E. R. , Suter Sonia M. , Uhlmann Wendy R. , Scherer Aaron M.
Published: August 2022

Informed consent is a foundational ethical and legal principle in human subjects research and clinical care. Yet, there is extensive debate over how much information must be disclosed to meet ethical goals and legal requirements, especially about non‐medical risks. In this online, survey‐based experiment of a diverse sample of the US general population, we explored one aspect of this debate by testing whether the level of detail included in informed consent regarding genetic anti‐discrimination protections alters individuals' willingness to participate in a hypothetical research study and their concerns regarding genetic discrimination. Participants were randomized to receive sample informed consent language with one of three levels of disclosure regarding the protections and limitations of the Genetic Information Nondiscrimination Act (GINA). Our sample (n = 1,195) had a mean age of 45.9 (SD = 17.9) years and 40% with ≤high school education. Participants were 51.3% female and 36.7% non‐Hispanic White. On average, those who received consent language with none of GINA's limitations highlighted were more willing to participate than those who were warned about various gaps in GINA. They also had significantly lower perceived risk of discrimination than those presented with the most information about limitations. Our study found that providing more comprehensive information about GINA notably lessened willingness to participate in the hypothetical studies, highlighting the need for clinicians and researchers to thoughtfully consider how to disclose anti‐discrimination risks in informed consent.
Foot gangrene following Tagraxofusp treatment for blastic plasmacytoid dendritic cell neoplasm: Case report
Authors: Sibai Jad , Chen RuiQi , Nabhani Ibrahim Al , Perusini Maria Agustina , Sibai Hassan
Published: August 2022

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy. It is associated with poor prognosis and heterogenous presentation. The CD123‐directed cytotoxin, Tagraxofusp, is a targeted therapy for BPDCN. Here, we report an 81‐year‐old female diagnosed with BPDCN. The patient was treated with Tagraxofusp and underwent a remarkably long remission (>20 months) without stem‐cell transplantation. She, however, experienced blue toe syndrome and left foot gangrene. We postulate that these previously unreported side effects were caused by microembolization. Characterization of the incidence of thrombo‐ and microembolizations in such a context, as well as prophylactic management options, are warranted.
Trends in all‐cause mortality and inpatient and outpatient visits for ambulatory care sensitive conditions during the first year of the COVID‐19 pandemic: A population‐based study
Authors: Kendzerska Tetyana , Zhu David T. , Pugliese Michael , Manuel Douglas , Sadatsafavi Mohsen , Povitz Marcus , Stukel Therese A. , To Teresa , Aaron Shawn D. , Mulpuru Sunita , Chin Melanie , Kendall Claire E. , Thavorn Kednapa , Robillard Rebecca , Gershon Andrea S.
Published: August 2022

Background

The impact of the COVID‐19 pandemic on the management of ambulatory care sensitive conditions (ACSCs) remains unknown.

Objectives

To compare observed and expected (projected based on previous years) trends in all‐cause mortality and healthcare use for ACSCs in the first year of the pandemic (March 2020 to March 2021).

Design, Setting and Participants

We conducted a population‐based study using provincial health administrative data on general adul population (Ontario, Canada).

Outcomes and Measures

Monthly all‐cause mortality, and hospitalizations, emergency department (ED) and outpatient visit rates (per 100,000 people at‐risk) for seven combined ACSCs (asthma, chronic obstructive pulmonary disease, angina, congestive heart failure, hypertension, diabetes, and epilepsy) during the first year were compared with similar periods in previous years (2016–2019) by fitting monthly time series autoregressive integrated moving‐average models.

Results

Compared to previous years, all‐cause mortality rates increased at the beginning of the pandemic (observed rate in March to May 2020 of 79.98 vs. projected of 71.24 [66.35–76.50]) and then returned to expected in June 2020—except among immigrants and people with mental health conditions where they remained elevated. Hospitalization and ED visit rates for ACSCs remained lower than projected throughout the first year: observed hospitalization rate of 37.29 versus projected of 52.07 (47.84–56.68); observed ED visit rate of 92.55 versus projected of 134.72 (124.89–145.33). ACSC outpatient visit rates decreased initially (observed rate of 4299.57 vs. projected of 5060.23 [4712.64–5433.46]) and then returned to expected in June 2020.
Drop‐offs in the isoniazid preventive therapy cascade among children living with HIV in western Kenya, 2015–2019
Authors: Onyango Dickens Otieno , van der Sande Marianne A. B. , Yuen Courtney M. , Mecha Jerphason , Matemo Daniel , Oele Elizabeth , Kinuthia John , John‐Stewart Grace , LaCourse Sylvia M.
Published: August 2022

Introduction

Isoniazid preventive therapy (IPT) can reduce the risk of tuberculosis (TB) in children living with HIV (CLHIV), but data on the outcomes of the IPT cascade in CLHIV are limited.

Methods

We evaluated the IPT cascade among CLHIV aged <15 years and newly enrolled in HIV care in eight HIV clinics in western Kenya. Medical record data were abstracted from September 2015 through July 2019. We assessed the proportion of CLHIV completing TB symptom screening, IPT eligibility assessment, IPT initiation and completion. TB incidence rate was calculated stratified by IPT initiation and completion status. Risk factors for IPT non‐initiation and non‐completion were assessed using Poisson regression with generalized linear models.

Results

Overall, 856 CLHIV were newly enrolled in HIV care, of whom 98% ([95% CI 97–99]; n = 841) underwent screening for TB symptoms and IPT eligibility. Of these, 13 (2%; 95% CI 1–3) were ineligible due to active TB and 828 (98%; 95% CI 97–99) were eligible. Five hundred and fifty‐nine (68%; 95% CI 64–71) of eligible CLHIV initiated IPT; median time to IPT initiation was 3.6 months (interquartile range [IQR] 0.5–10.2). Overall, 434 (78%; 95% CI 74–81) IPT initiators completed. Attending high‐volume HIV clinics (aRR = 2.82; 95% CI 1.20–6.62) was independently associated with IPT non‐initiation. IPT non‐initiation had a trend of being higher among those enrolled in the period 2017–2019 versus 2015–2016 (aRR = 1.91; 0.98–3.73) and those who were HIV virally non‐suppressed (aRR = 1.90; 95% CI 0.98–3.71). Being enrolled in 2017–2019 versus 2015–2016 (aRR = 1.40; 1.01–1.96) was independently associated with IPT non‐completion. By 24 months after IPT screening, TB incidence was four‐fold higher among eligible CLHIV who never initiated (8.1 per 1000 person years [PY]) compared to CLHIV who completed IPT (2.1 per 1000 PY; rate ratio [RR] = 3.85; 95% CI 1.08–17.15), with a similar trend among CLHIV who initiated but did not complete IPT (8.2/1000 PY; RR = 4.39; 95% CI 0.82–23.56).

Conclusions

Despite high screening for eligibility, timely IPT initiation and completion were suboptimal among eligible CLHIV in this programmatic cohort. Targeted programmatic interventions are needed to address these drop‐offs from the IPT cascade by ensuring timely IPT initiation after ruling out active TB and enhancing completion of the 6‐month course to reduce TB in CLHIV.
Correcting for selection bias in HIV prevalence estimates: an application of sample selection models using data from population‐based HIV surveys in seven sub‐Saharan African countries
Authors: Palma Anton M. , Marra Giampiero , Bray Rachel , Saito Suzue , Awor Anna Colletar , Jalloh Mohamed F. , Kailembo Alexander , Kirungi Wilford , Mgomella George S. , Njau Prosper , Voetsch Andrew C. , Ward Jennifer A. , Bärnighausen Till , Harling Guy
Published: August 2022

Introduction

Population‐based biomarker surveys are the gold standard for estimating HIV prevalence but are susceptible to substantial non‐participation (up to 30%). Analytical missing data methods, including inverse‐probability weighting (IPW) and multiple imputation (MI), are biased when data are missing‐not‐at‐random, for example when people living with HIV more frequently decline participation. Heckman‐type selection models can, under certain assumptions, recover unbiased prevalence estimates in such scenarios.

Methods

We pooled data from 142,706 participants aged 15–49 years from nationally representative cross‐sectional Population‐based HIV Impact Assessments in seven countries in sub‐Saharan Africa, conducted between 2015 and 2018 in Tanzania, Uganda, Malawi, Zambia, Zimbabwe, Lesotho and Eswatini. We compared sex‐stratified HIV prevalence estimates from unadjusted, IPW, MI and selection models, controlling for household and individual‐level predictors of non‐participation, and assessed the sensitivity of selection models to the copula function specifying the correlation between study participation and HIV status.

Results

In total, 84.1% of participants provided a blood sample to determine HIV serostatus (range: 76% in Malawi to 95% in Uganda). HIV prevalence estimates from selection models diverged from IPW and MI models by up to 5% in Lesotho, without substantial precision loss. In Tanzania, the IPW model yielded lower HIV prevalence estimates among males than the best‐fitting copula selection model (3.8% vs. 7.9%).

Conclusions

We demonstrate how HIV prevalence estimates from selection models can differ from those obtained under missing‐at‐random assumptions. Further benefits include exploration of plausible relationships between participation and outcome. While selection models require additional assumptions and careful specification, they are an important tool for triangulating prevalence estimates in surveys with substantial missing data due to non‐participation.
Noninvasive Evaluation of the Notch Signaling Pathway via Radiomic Signatures Based on Multiparametric MRI in Association With Biological Functions of Patients With Glioma: A Multi‐institutional Study
Authors: Shen Nanxi , Lv Wenzhi , Li Shihui , Liu Dong , Xie Yan , Zhang Ju , Zhang Jiaxuan , Jiang Jingjing , Jiang Rifeng , Zhu Wenzhen
Published: August 2022

Background

Noninvasive determination of Notch signaling is important for prognostic evaluation and therapeutic intervention in glioma.

Purpose

To predict Notch signaling using multiparametric (mp) MRI radiomics and correlate with biological characteristics in gliomas.

Study Type

Retrospective.

Population

A total of 63 patients for model construction and 47 patients from two public databases for external testing.

Field Strength/Sequence

A 1.5 T and 3.0 T, T1‐weighted imaging (T1WI), T2WI, T2 fluid attenuated inversion recovery (FLAIR), contrast‐enhanced (CE)‐T1WI.

Assessment

Radiomic features were extracted from CE‐T1WI, T1WI, T2WI, and T2FLAIR and imaging signatures were selected using a least absolute shrinkage and selection operator. Diagnostic performance was compared between single modality and a combined mpMRI radiomics model. A radiomic–clinical nomogram was constructed incorporating the mpMRI radiomic signature and Karnofsky Performance score. The performance was validated in the test set. The radiomic signatures were correlated with immunohistochemistry (IHC) analysis of downstream Notch pathway components.

Statistical Tests

Receiver operating characteristic curve, decision curve analysis (DCA), Pearson correlation, and Hosmer–Lemeshow test. A P value < 0.05 was considered statistically significant.

Results

The radiomic signature derived from the combination of all sequences numerically showed highest area under the curve (AUC) in both training and external test sets (AUCs of 0.857 and 0.823). The radiomics nomogram that incorporated the mpMRI radiomic signature and KPS status resulted in AUCs of 0.891 and 0.859 in the training and test sets. The calibration curves showed good agreement between prediction and observation in both sets (P= 0.279 and 0.170, respectively). DCA confirmed the clinical usefulness of the nomogram. IHC identified Notch pathway inactivation and the expression levels of Hes1 correlated with higher combined radiomic scores (r = −0.711) in Notch1 mutant tumors.

Data Conclusion

The mpMRI‐based radiomics nomogram may reflect the intratumor heterogeneity associated with downstream biofunction that predicts Notch signaling in a noninvasive manner.

Evidence Level

3

Technical Efficacy

Stage 2
Placement of catheters without magnetic sensors in the coronary sinus without fluoroscopic guidance: Feasibility and safety evaluation
Authors: Hoshiyama Tadashi , Sumi Hitoshi , Kaneko Shozo , Kawahara Yusei , Ito Miwa , Kanazawa Hisanori , Takashio Seiji , Yamamoto Eiichiro , Matsushita Kenichi , Tsujita Kenichi
Published: August 2022

Background

A three‐dimensional (3D) mapping system is essential to reduce radiation exposure during catheter ablation. When using the CARTO 3D mapping system, only the catheter with magnetic sensor can visualize its location. However, once target chamber matrix is created using the catheter, even the catheters without magnetic sensors (CWMS) can enable visualization. We aimed to investigate the feasibility and safety of placing a CWMS in the coronary sinus (CS) without fluoroscopic guidance.

Methods

The study group comprised 88 consecutive patients who underwent catheter ablation. CWMS placement was performed without fluoroscopic guidance in 47 patients and with fluoroscopic guidance in 41 patients. Placement without fluoroscopic guidance was performed after creating a visualization matrix of the CS, right atrium, and superior vena cava using a catheter with a magnetic sensor. Feasibility and safety were compared between the two groups.

Results

Successful catheter placement was achieved in all patients without fluoroscopic guidance, with no inter‐group difference in the median procedure time: with guidance, 120.0 [96.0–135.0] min, and without guidance, 110.0 [97.5–125.0] min; p = .22. However, radiation exposure was significantly shorter, and the effective dose was lower without fluoroscopic guidance (0 [0–17.5] s and 0 [0–0.004] mSv, respectively) than with fluoroscopic guidance (420.0 [270.0–644.0] s and 0.73 mSv [0.36–1.26], respectively); both p < .001.

Conclusions

CWMS placement without fluoroscopic guidance is feasible, safe to perform, and does not involve complications. Our technique provides an option to decrease radiation exposure during catheter ablation and electrophysiological testing.