bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of CYP3A4/5 and ABC transporter polymorphisms on osimertinib plasma concentrations in Japanese patients with non-small cell lung cancer
Authors: Yokota Hayato , Sato Kazuhiro , Sakamoto Sho , Okuda Yuji , Fukuda Natsuki , Asano Mariko , Takeda Masahide , Nakayama Katsutoshi , Miura Masatomo 
Published: July 2022

Abstract
Background: The effects of polymorphisms in CYP3A4 (20230G>A), CYP3A5 (6986A>G), ABCB1 (1236C>T, 2677G>T/A, 3435C>T), ABCG2 (421C>A), and ABCC2 (-24C>T) on the area under the concentration-time curve (AUC) of osimertinib in 23 patients with non-small cell lung cancer were investigated.Methods: Blood sampling was performed just prior to and at 1, 2, 4, 6, 8, 12, and 24 h after osimertinib administration at the steady-state on day 15 after beginning therapy.Results: There were significant correlations of the area under the plasma concentration-time curve over the last 24-h dosing interval (AUC0-24) of osimertinib with age (P = 0.038), serum albumin (P = 0.002), and serum creatinine (P = 0.012). Additionally, there were significant differences in the AUC0-24 of osimertinib among the groups administered vonoprazan, histamine 2-receptor antagonists or esomeprazole, and no acid suppressants (P = 0.021). By contrast, there were no significant differences in the AUC0-24 of osimertinib between genotypes of CYP3A4/5 or ABC transporters. Furthermore, there were no significant differences in the AUC0-24 of osimertinib between patients with diarrhea, skin rash, or hepatotoxicity and those without these conditions. In multivariate analysis, only serum albumin value was an independent factor predicting the AUC0-24 of osimertinib. Conclusions: Analysis of CYP3A4/5 and ABC transporter polymorphisms before osimertinib therapy may not predict the efficacy or side effects of osimertinib. However, lower serum albumin values were associated with an increase in the AUC0-24 of osimertinib. After beginning osimertinib therapy, periodic measurement of serum albumin values should be performed.
COVID-19 outcomes in people living with HIV: peering through the waves
Authors: Sales Thaís Lorenna Souza , Souza-Silva Maíra Viana Rego , Delfino-Pereira Polianna , Neves João Victor Baroni , Sacioto Manuela Furtado , Assis Vivian Costa Morais , Duani Helena , de Oliveira Neimy Ramos , Sampaio Natália da Cunha Severino , Ramos Lucas Emanuel Ferreira , Schwarzbold Alexandre Vargas , Jorge Alzira de Oliveira , Scotton Ana Luiza Bahia Alves , de Castro Bruno Mateus , Silva Carla Thaís Cândida Alves da , Ramos Carolina Marques , Anschau Fernando , Botoni Fernando Antonio , Grizende Genna Maira Santos , Nascimento Guilherme Fagundes , Ruschel Karen Brasil , Menezes Luanna Silva Monteiro , Castro Luís César , Nasi Luiz Antônio , Carneiro Marcelo , Godoy Mariana Frizzo , Nogueira Matheus Carvalho Alves , Júnior Milton Henriques Guimarães , Ziegelmann Patricia Klarmann , Almeida Rafaela Charão , Francisco Saionara Cristina , Neto Sidney Teodoro Silveira , Araújo Silvia Ferreira , Avelino-Silva Thiago Junqueira , Aliberti Márlon Juliano Romero , Pires Magda Carvalho , Silva Eduardo Sérgio da , Marcolino Milena Soriano 
Published: July 2022

Abstract
Background: HIV infection remains a public health concern, especially in low- and middle-income countries. Data regarding exposure of COVID-19 in HIV infected patients remains scarce. We evaluated clinical characteristics and outcomes of COVID-19 patients infected with HIV, and compared with a paired sample without HIV infection. Methods: This is a substudy of a large Brazilian cohort that comprised two periods (2020 and 2021). Data was obtained through the retrospective review of medical records to collect variables of interest and primary outcomes: intensive care admission, mechanical ventilation and death. COVID-19 patients infected with HIV were compared to COVID-19 patients without concomitant diagnosis of HIV infection using the Chi-Square Test and Fisher's exact test for categorical variables and the Wilcoxon test for numerical variables. Both groups were matched for age, sex, number of comorbidities and hospital of origin using the technique of propensity score matching (up to 4:1).Results: Throughout the study, 17,101 COVID-19 patients were hospitalized, 130 (0.76%) of these infected with HIV. The median age was 54 (IQR: 43.0;64.0) years in 2020 and 53 (IQR: 46.0;63.5) years in 2021, with predominance of females in both periods. People living with HIV (PLHIV) and their controls showed similar prevalence for the admission in the ICU and mechanical ventilation requirement in the two periods, with no significant differences. In 2020, in-hospital mortality was higher in the PLHIV compared to the controls (27.9% vs 17.7%; p=0.049), but there was no difference in mortality between groups in 2021 (25.0% vs 25.1%; p>0.999). Conclusion: Our results reiterate that PLHIV were at higher risk of COVID-19 mortality in the early stages of the pandemic, however, this finding did not sustain in 2021, indicating that measures such as large-scale immunization programs have successfully contributed to reducing the excess mortality seen in PLHIV.
Periodontal ligament stem cells inhibit THP-1 macrophage pyroptosis via modulating the NF-κB/NLRP3/GSDMD signaling axis
Authors: Wang Wenxuan , Fan Chun , Yu Xinbo , Qiu Xu , Hu Yingzhe , Li Shuhan , Gao Xiangru , Ji Qiuxia 
Published: July 2022

Abstract
Background: To investigate the pathological crosstalk between pyroptosis and periodontitis by addressing the following questions: 1) Does pyroptosis play any pathobiological roles in the onset and progression of periodontitis?; 2) Are the localized periodontal macrophages major cell type in pyroptosis?; 3) Can in vitro stimulation by Porphyromonas gingivalis-derived lipopolysaccharide (P.g-LPS) and adenosine triphosphate (ATP) in THP-1 macrophages induce pyroptosis via activation of the NF-κB/NLRP3/GSDMD signaling axis?; and 4) Is there any paracrine effect of periodontal ligament stem cells (PDLSCs) on the NF-κB/NLRP3/GSDMD pathway in pyroptosis?Methods: Clinical periodontitis tissue samples were collected from voluntarily enrolled participants who visited the Dental Clinic of the Affiliated Hospital of Qingdao University. In vitro, THP-1 macrophage pyroptosis was induced by treating with P.g-LPS in combination with ATP. The qRT-PCR, western blotting, and ELISA methods were used to determine the expression levels of NF-κB, NLRP3, caspase-1, ASC, GSDMD, IL-1β, and IL-18. We used the 2ʹ,7ʹ‑dichlorodihydrofluorescein diacetate fluorescence probe to measure ROS levels in THP-1 cells. The caspase-1 activity assay, cytotoxicity assay, and double staining with Hoechst 33342 and propidium iodide were performed in pyroptotic THP-1 macrophages to test the paracrine effect of human PDLSCs on pyroptosis. Results: High expressions of the canonical pyroptosis-associated factors were detected in periodontitis gingival tissues from patients compared to the healthy controls. P.g-LPS treatment exhibited significant stimulation of the canonical pyroptotic effectors, including NF-κB, NLRP3, caspase-1, GSDMD-N, IL-1β, and IL-18 at both mRNA and protein levels. Furthermore, induction of pyroptosis drastically increased the caspase-1 activity, the release of lactate dehydrogenase, and the percentage of cells with damaged membranes, but these pathological effects could be ameliorated via paracrine effects of PDLSCs. Conclusions: Macrophage pyroptosis is an important contributor to the development of periodontitis, while PDLSCs can significantly attenuate the pyroptosis process induced by P.g-LPS/ATP by inhibiting the NF-κB/NLRP3/GSDMD signaling through its paracrine effects in vitro. These evidences cumulatively confirm the immunomodulatory roles of PDLSCs in periodontitis and may be exploited as an effective therapeutic target.
Giant piezoresistivity in a van der Waals material induced by intralayer atomic motions
Authors: Tang Lingyun , Mao Zhong-Quan , Wang Chutian , Fu Qi , zhang Yichi , Shen Jingyi , Yin Yuefeng , Shen Bin , Tan Dayong , Li Qian , Wang Yonggang , Medhekar Nikhil , Wu Jie , Yuan Huiqiu , Li Yanchun , Fuhrer Michael , Zheng Changxi 
Published: July 2022

Abstract
The presence of the van der Waals (vdW) gap in layered materials creates a wealth of intriguing phenomena different to their counterparts in conventional materials. For example, pressurization can generate a large anisotropic lattice shrinkage along the vdW stacking orientation and/or a significant interlayer sliding, and many of the exotic pressure-dependent properties derive from these mechanisms. Here we report a giant piezoresistivity in pressurized \(\beta \text{’}\)-In2Se3. Upon compression, a six-orders-of-magnitude drop of electrical resistivity is obtained below 1.2 GPa in \(\beta \text{’}\)-In2Se3 flakes, yielding a giant piezoresistive gauge \({\pi }_{P}\) of -5.33 GPa− 1. Simultaneously, the sample undergoes a semiconductor-to-semimetal transition without a structural phase transition. Surprisingly, linear dichroism study and theoretical first principles modelling show that these phenomena arise not due to shrinkage or sliding at the vdW gap, but rather are dominated by the layer-dependent atomic motions inside the quintuple layer, mainly from the shifting of middle Se atoms to their high-symmetric location. Our work not only provides a prominent piezoresistive material but also points out the importance of intralayer atomic motions beyond vdW gap.
Water Quality Modelling and Evaluation at Marine Outfalls
Authors: saie Yasser El 
Published: July 2022

Abstract
The increasing water demand of urban and industrial areas in most semi-arid and arid coastal cities led planners to seek renewable alternative water sources and resources. In the past decade, Egypt has launched many large-scale projects along its Red Sea and Mediterranean coasts to cope with the continuous increase of population and urban and industrial developments. Desalination is the most feasible solution to the huge water demand in the region, especially due to the known and limited water resources of the Nile and expected drought due to climate change and upstream dams’ construction. Reverse osmosis desalination plants have become an important source of freshwater production in Egypt. However, the treatment of brine wastewater is still a challenging problem. Hyper saline water effluent as a by-product of seawater desalination, has a negative impact on the marine ecosystem, if discharged inadequately. In this work, a simulation method was proposed to design a safe disposal system for brine effluents. This study uses the model of (CORMIX v 9.0) near-field hydrodynamic model to simulate, predict and manage the brine discharge dispersion and dilution behavior, and assess the initial dilution discharged into coastal water areas through different outfall systems configurations. The research will be applied to desalination plants located along the Red Sea and the Mediterranean Sea coasts. Based on the simulation results, the design of desalination plants reject brine removal system with a multi-port diffuser will be determined. The design parameters are the, diameter, length and number of ports in the effluent system. These optimized simulation frameworks provide planners with effective tools to meet environmental standards while achieving economic or cost-effectiveness and Hydrodynamic performance that is appropriate and up to date. Applicability of the proposed method was demonstrated by a case study.
The Presence of Antineutrophil Cytoplasmic Antibodies and Antiphospholipid Antibodies in Severe Acute Respiratory Syndrome Coronavirus 2 patients: A Case-Control Study among Sudanese Patients
Authors: Aldeen Mohammad Shams , Masaad Musa Logman , Azhary Ayman , haj Abdulomez Suliman al , Alzebier Mohammed Ahmed , Abdalgader Motasim , Aman Farag Alla , Ismail Salahaldeen , Abuzeid Nadir , Musa Abdualmoniem , Mengistu Samuel Tekle , Hamida Mohammed Elfatih 
Published: July 2022

Abstract
Patients infected with COVID-19 are at increased risk for thrombosis, suggesting an important role for COVID-19-induced coagulopathy. This study aimed to investigate the presence of prothrombotic antineutrophil cytoplasmic antibodies (ANCA) and antiphospholipid antibodies (aPL) in the course of COVID-19 infection and to correlate these markers with severity and fatality, suggesting that COVID-19-induced autoimmune thrombosis is an axis in the inflammatory circuit of infection. To investigate this, we conducted a case-control study in which the cases had a positive reverse transcription-polymerase chain reaction (RT-PCR) and the controls had a negative result, in addition to confirming that the SARS-CoV-2 nucleocapsid antibodies were negative. An indirect immunofluorescence assay using granulocyte biochips (AESKU slides from AESKU DIAGNOSTICS- Germany) was used to detect ANCA, as well as multiplex ELISA for the detection of antiphospholipid antibodies for all patients with COVID-19 and for the control group. The results showed that of the 45 cases, 1/45(2.2%) revealed positive for aPL and 7/45(15.6%) tested positive for ANCA, 5 were men and 2 were females; one case tested positive for both aPL and ANCA. A cytoplasmic reaction against eosinophils was observed in 2 cases; both were positive for ANCA. Other markers (CRP, APTT, PT, INR ESR, and neutrophil and lymphocyte counts) were included in the study, along with demographic data. NO aPL or ANCA was detected in the control group. These findings suggest that aPL and ANCA are induced by inflammation of COVID-19 and possibly contribute to severity and mortality.
CausNet : Generational orderings based search for optimal Bayesian networks via dynamic programming with parent set constraints
Authors: Sharma Nand , Millstein Joshua 
Published: July 2022

Abstract
Background : Finding a globally optimal Bayesian Network using exhaustive search is a problem with super-exponential complexity, which severely restricts the number of variables that it can work for. We implement a dynamic programming based algorithm with built-in dimensionality reduction and parent set identification. This reduces the search space drastically and can be applied to large-dimensional data. We use what we call ‘generational orderings’ based search for optimal networks, which is a novel way to efficiently search the space of possible networks given the possible parent sets. The algorithm supports both continuous and categorical data, and categorical as well as survival outcomes. Results : We demonstrate the efficacy of our algorithm on both synthetic and real data. In simulations, our algorithm performs better than three state-of-art algorithms that are currently used extensively. We then apply it to an Ovarian Cancer gene expression dataset with 513 genes and a survival outcome. Our algorithm is able to find an optimal network describing the disease pathway consisting of 6 genes leading to the outcome node in a few minutes on a basic computer. Conclusions : Our generational orderings based search for optimal networks, is both efficient and highly scalable approach to finding optimal Bayesian Networks, that can be applied to 1000s of variables. Using specifiable parameters - correlation, FDR cutoffs, and in-degree - one can increase or decrease the number of nodes and density of the networks. Availability of two scoring option - BIC and Bge - and implementation for survival outcomes and mixed data types makes our algorithm very suitable for many types of high dimensional data in a variety of fields.
Inhibition of SARS-COV-2 Receptor-Binding domain/ACE2 by Bazedoxifene
Authors: omotuyi olaposi , Olatunji Olusina M. , Nash Oyekanmi , Oyinloye Babatunji , Soremekun Opeyemi , Ijagbuji Ayodeji , Fatumo Segun 
Published: July 2022

Abstract
Coronavirus spike glycoprotein (GP)-Receptor Binding Domain (RBD) and its interaction with host receptor angiotensin converting enzyme 2 (ACE2) is one of the most structurally understood but therapeutically untapped aspect of COVID-19 pathogenesis. In this study, Fragment-based lead discovery was conducted to identify potential lead anti-SARS-COV-2 drug candidate acting at RBD/ACE2 interface. From the original 12000 chemical building blocks, benzimidazole (BAZ) scaffold was identified. Fingerprint-based similarity search of the FDA-approved drug library for BAZ-containing compounds identified 12 drugs with the benzimidazole-like substructure. When these compounds were re—docked into GP/ACE2 interface, the consensus docking identified bazedoxifene as the hit. In vitro RBD/ACE2 inhibition kinetics showed micromolar IC50 value (1.237 μM) in the presence of bazedoxifene. Molecular dynamics simulation of RBD/ACE2 in the presence BAZ resulted in loss of contact and specific hydrogen-bond interaction required for RBD/ACE2 stability. Taken together, these findings identified benzimidazole scaffold as a building block for developing novel RBD/ACE2 complex inhibitor and provided mechanistic basis for the use of bazedoxifene as a repurposable drug for the treatment of COVID-19 acting at RBD/ACE2 interface.
Omicron SARS-CoV-2 Neutralization by Immunoglobulin Preparations Manufactured from Plasma Collected in the US and Europe
Authors: Farcet Maria R. , Karbiener Michael , Knotzer Simone , Schwaiger Julia , Kreil Thomas R. 
Published: July 2022

Abstract
After >2 years of the COVID-19 pandemic, immunoglobulins (IG) contain highly potent SARS-CoV-2 neutralizing antibodies, based on the large proportion of US plasma donors who have gone through COVID-19 or vaccination against. Neutralization of Omicron SARS-CoV-2 by antibodies generated after non-Omicron infection or vaccination has been lower though, raising concerns about the potency of IG against this new virus variant. Also, as plasma collected in the US remains the main source of IG, the neutralization of SARS-CoV-2 for plasma collected elsewhere has been less well studied. Here, we confirm Omicron neutralization by US as well as EU plasma-derived IG lots.
Multifocal Invasive Streptococcus Pyogenes Infection in Previously Healthy Child: A Rare Case Report
Authors: Holmes Connor , Moolman Nico , Spafford Peter 
Published: July 2022

Abstract
Background: Invasive streptococcus pyogenes infections are rarely seen in healthy children. The multifocal nature of the following case is unusual and presents a diagnostic and therapeutic challenge for the treating physician. Case presentation: In this case report, we discuss an otherwise healthy 11-year-old boy with a multifocal invasive streptococcus pyogenes infection presenting with a myriad of musculoskeletal complications at distant sites. He suffered from multiple abscesses, septic arthritis of sternoclavicular joint and multiple sites of osteomyelitis, osteitis and tenosynovitis in the neck hand and foot. A significant course of intravenous antibiotic therapy was required for resolution of disease.Conclusions: Streptococcus pyogenes is a common culprit in head and neck infections. This case is unique because of the multifocal nature of our patient’s infection. The Otolaryngologist – Head and Neck Surgeon should acknowledge the potential for rare and diffuse complications from invasive streptococcus pyogenes infection.
Speech Quefrency Transform (SQT)
Authors: Hasanain Ahmad Zuhair , Kepuska Veton Z , Silaghi Marius Calin , Kostanic Ivica N 
Published: July 2022

Abstract
Human speech consists mainly of three components: a glottal signal, a vocal tract response, and a harmonic shift. The three respectively correlate with the intonation (pitch), the formants (timbre), and the speech resolution (depth). Adding the intonation of the Fundamental Frequency (FF) to Automatic Speech Recognition (ASR) systems is necessary. First, the intonation conveys a primitive para-language. Second, its speaker-tuning reduces background noises to clarify acoustic observations. Third, extracting the speech features is more efficient when they are computed together at the same time.This work introduces a frequency-modulation model, a novel quefrency-based speech features' extraction that is named Speech Quefrency Transform (SQT), and its proper quefrency scaling and transformation function. The cepstrums, which are spectrums of spectrums, are suggested in time unit accelerations, whereby the discrete variable, the quefrency, is measured in Hertz-per-microsecond. The extracted features are comparable to Mel-Frequency Cepstral Coefficients (MFCC) integrated within a quefrency-based pitch tracker. The SQT transform directly expands time samples of stationary signals (i.e., speech) to a higher dimensional space, which can help generative Artificial Neural Networks (ANNs) in unsupervised Machine Learning and Natural Language Processing (NLP) tasks. The proposed methodologies, which are a scalable solution that is compatible with dynamic and parallel programming for refined speech and cepstral analysis, can robustly estimate the features after applying a matrix multiplication in less than a hundred sub-bands, preserving precious computational resources.
Towards the coordinated and fit-for-purpose deployment of Unmanned Aerial Systems (UASs) for flood risk management in England
Authors: Giannitsopoulos Michail L. , Leinster Paul , Butler David , Smith Mike , Rivas Casado Mónica 
Published: July 2022

Abstract
Preparedness for flood emergency response is crucial for effective flood management. The need for advanced flood decision support tools that aid flood management has been recognized by several authors. This work examines the variability that currently exists across England with regard to the Unmanned Aerial System (UAS) data collection and processing strategy in flood emergency events. Expert elicitation was carried out using a tailored questionnaire about UAS deployment in three flood emergency scenarios. The survey highlighted that reduced equipment assembly time, a national network of appropriately qualified UAS pilots and the effective UAS deployment when on-site, can reduce the response time to flood emergency. For improved comparability and reduced bias in data collection and interpretation, clear guidelines on which data products are most beneficial for particular purposes, processing time required, platform and sensor selection may also be necessary. We consider that releasing a comprehensive documentation pack, which includes guidelines, standards and protocols that detail the methods, tools, technology, quantity and quality of data, to UAS pilots on a flood emergency call, will enhance the timely response.
Effectiveness of environmental surveillance of SARS-CoV-2 as an early warning system during the first year of the COVID-19 pandemic: a systematic review
Authors: Hyllestad Susanne , Myrmel Mette , Lomba Jose Antonio Baz , Jordhøy Fredrik , Schipper Svanhild Kjørsvik , Amato Ettore 
Published: July 2022

Abstract
Since infected persons shed SARS-CoV-2 in faeces before symptoms appear, environmental surveillance (ES) may serve as an early warning system (EWS) for COVID-19 and new variants of concern. The ES of SARS-CoV-2 has been widely reviewed; however, its effectiveness as an EWS for SARS-CoV-2 in terms of timeliness, sensitivity and specificity has not been systematically assessed. We conducted a systematic review to identify and synthesise evidence on the ES of SARS-CoV-2 as an EWS to evaluate the added value for public health. Of 1,014 studies identified, we considered 29 for a qualitative synthesis of the timeliness of ES as an EWS for COVID-19, while six studies were assessed for the ability to detect new variants and two for both aims. The synthesis indicates ES may serve as an EWS of 1–2 weeks. ES could complement clinical surveillance for SARS-CoV-2; however, its cost–benefit value for public health decisions needs to be assessed based on the stage of the pandemic and resources available. Studies focusing methodological knowledge gaps as well as how to use and interpret ES signals for public health actions are needed, as is the sharing of knowledge within countries/areas with long experience of such surveillance.