bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug-related problem (DRP) penggunaan antidiabetik oral dan insulin pada pasien diabetes melitus tipe II rawat inap di RSU Royal Prima Medan
Authors: Neswita Elfia , Halu Brian Elberth , Razoki  , Lubis Asyrun lkhairi , Yunus Muhammad , Nurasni  , Nababan Octavian Ashido
Published: July 2023

Diabetes mellitus merupakan sekolompok gangguan metabolism yang ditandai oleh hiperglikemia yang menjadi penyebab kematian hingga 80% pada Negara yang berpenghasilan rendah dan menengah. Diabetes mellitus tipe II adalah bentuk diabetes yang paling umum terjadi. Tujuan pengelolaan terapi diabetes mellitus tipe II adalah untuk mengurangi risiko komplikasi mikrovaskular dan makrovaskular, mengurangi angka kematian, dan meningkatkan kualitas hidup. Pengobatan diabetes melitus memerlukan watu lama. Masalah yang timbul akibat komplikasi pada diabetes melitus akan meningkatkan kesulitan dalam pengobatan pasien. Ini berpotensi menyebabkan munculnya masalah terkait obat Drug Related Problem (DRP). Drug-Related Problems merujuk pada kejadian yang tidak diharapkan yang dialami oleh pasien dan dapat mengganggu keberhasilan terapi obat yang diberikan. Metode penelitian pada penelitian ini dengan menetapkan obat yang akan dievaluasi yang berupa obat antidiabetik oral yang digunakan selama menjalani terapi diabetes mellitus tipe II dan terapi insulin.hasil penelitian menunjukan bahwa terdapat 26 orang pasien yang mengalami Drug-Related Problems maupun tidak (50%). Pasien yang mengalami Drug Related Problem aktual sebanyak 10.2% (6 orang pasien) sedangka yang mengalami Drug Related Problem Potensial sebanyak 46.15% (24 pasien) dari total 52 pasien diabetes mellitus tipe II yang menjadi sampel penelitian ini. Ada dua kategori Drug Related Problem yang terjadi, yaitu Drug Related Problem terkait terapi obat tambahan dengan jumlah 2,17% (2 kejadian), dan Drug Related Problem terkait reaksi yang tidak diinginkan dari obat (Adverse Drug Reaction) dengan jumlah 4 kejadian (7,7%).
Trustworthy AI Principles to Face Adversarial Machine Learning: A Novel Study
Authors: CH.E.N. Sai Priya  , Manas Kumar Yogi
Published: July 2023

Artificial Intelligence (AI) has witnessed significant advancements in recent years, enabling its widespread adoption across various domains. However, this progress has also given rise to new challenges, particularly in the context of adversarial machine learning. Adversarial attacks exploit vulnerabilities in AI models, resulting in their misclassification or misbehaviour. To address this critical issue, it is crucial to develop trustworthy AI systems that can withstand such adversarial threats. This paper presents a comprehensive study that covers the types of adversarial machine learning cyber-attacks, methods employed by adversaries to launch such attacks, effective defence mechanisms, and potential future directions in the field. It starts by exploring various types of adversarial ML attacks, characteristics and potential consequences of each attack type, emphasizing the risks they pose to privacy, security, and fairness in AI systems and delving into the methods employed by adversaries to launch adversarial ML attacks. By understanding the tactics used by adversaries, researchers and practitioners can develop robust defence mechanisms that can withstand these attacks. Building upon this understanding, a range of defence strategies can be invented for defending against adversarial ML attacks and emerging research areas, such as the integration of secure multi-party computation, differential privacy, and federated learning are used to enhance the resilience of AI models. By understanding the nature of adversarial attacks and implementing effective defence strategies, AI systems can be fortified against malicious manipulations. The findings of this study contribute to the development of trustworthy AI systems, ensuring their resilience, transparency, and fairness.
Implementation of Automated Water based Level Management Model by using SCADA system and PLC
Authors: Abdulwahid Maan M. , Abdullah Haifat K. , Ateah Wasnaa M. , Ahmed Saja
Published: July 2023

This research developed a SCADA model for water management in a tank that is utilized for regulating and controlling power production and distribution automation for energy quality. The goal of this work is to create a model for water change controlled by a motor to handle the speed of filling and discharging the water within the tank, and as a water management procedure, such procedure will be performed by using the PLC controller connected to an HMI screen to achieve reliable management. The protocol utilized is the Modbus-based TCP protocol, which is suitable for low-cost systems and models. The suggested methodology may be used in big water tank stations to manage filling operations automatically and efficiently. In the future, the management method might be done wirelessly by employing a client software application with a specialized configuration.
Patologias associadas à deficiências na síntese do grupo heme
Authors: Bueno Beatriz Baquião , Soares Valéria Silva , Oliveira Célia Figueiredo de
Published: July 2023

As Porfirias são doenças neurológicas ou cutâneas associadas a deficiências hereditárias ou adquiridas, caracterizadas pela deficiência parcial na atividade de uma das enzimas da via de biossíntese do grupo heme, o que leva a uma diminuição dos níveis deste grupamento e ao acúmulo de seus precursores metabólicos. A primeira fase da biossíntese do grupo heme ocorre na mitocôndria, as fases intermediárias ocorrem no citosol e as fases finais ocorrem novamente na mitocôndria. Existem diversos fatores que participam do desencadeamento dessa doença, como fármacos, bebidas alcoólicas, hormônios, dietas, estresse, exposição aos raios solares, entre outros. A classificação das Porfirias é feita de acordo com a origem dos precursores em excesso, sendo, então, Porfirias Eritropoéticas ou Hepáticas. Também podem ser classificadas em Agudas e Crônicas, de acordo com as manifestações clínicas. Assim, sintomas neuropsiquiátricos, dores abdominais, vômitos, neuropatia aguda, convulsões e distúrbios mentais como alucinações, depressão, paranoia e ansiedades são referentes ao aspecto agudo. Já em casos crônicos, a manifestação clínica se dá sob a forma de fotossensibilidade cutânea. O tratamento é realizado após a descoberta dos sintomas. Sendo a Porfiria uma doença considerada rara e com poucos estudos relacionados a ela, este trabalho abrange suas principais características, diferenciando-a segundo sua classificação.
Influência do protocolo de remoção de resíduos de cimentos à base de resina epóxi sobre a interface de adesão com o adesivo universal, utilizado na estratégia condiciona-e-lava
Authors: Da Costa Neto Paulo Firmino , Gelio Mariana Bena , De Souza Elisângela Maria Pereira , Monteiro Jardel Camilo do Carmo , Jorge Júnior Adirson , Leandrin Thais Piragine , Saad José Roberto Cury , Kuga Milton Carlos
Published: July 2023

Objetivo: Avaliar o a influência da remoção de resíduos de dois cimentos à base de resina epóxi (SPL, Sealer Plus ou S26, Sealer 26), com etanol a 95% (ETA) ou xilol (XIL), na interface de adesão entre o sistema adesivo universal (SBU, Scotchbond Universal), utilizado na estratégia condiciona-e-lava, e o substrato dentinário da coroa dental, por meio da avaliação da resistência de união (RU), avaliada pelo teste de microcisalhamento, e análise do padrão de falha adesiva. Materiais e métodos: A face vestibular de quarenta coroas de dentes bovinos ex vivo foram preparadas e dividas e quatro grupos (n=10), de acordo com a composição química do cimento endodôntico (SPL ou S26) e protocolo de remoção dos resíduos (ETA ou XIL): SPL+ETA, SPL+XIL, S26+ETA e S26+XIL. Imediatamente após a impregnação da dentina e remoção dos resíduos do cimento, de acordo com o protocolos selecionado, a superfície dentinária foi condicionada com ácido fosfórico a 27% e aplicado o adesivo universal (SBU). Em seguida, 4 corpos de prova de resina composta foram fixados no local e, 24h após, submetidos ao teste de microcisalhamento e análise do padrão de fratura. Os dados de resistência de união foram analisados pelo teste de ANOVA a 2 critérios. Resultados:S26+ETA e S26+XIL demonstraram menores valores de RU em relação a SPL+XIL e S26+XIL (P < 0,05). Não houve diferença entre SPL+ETA e S26+S26 ou SPL+XIL e S26+S26 (P > 0,05). Conclusão: O xilol é o protocolo mais favorável para a remoção de resíduos do cimento à base de resina epóxi, independentemente da composição química do material, sobre a interface de adesão com o adesivo universal (SBU), utilizado na estratégia condiciona-e-lava.
A materialidade como cultura: nos tornamos com as coisas
Authors: Queiroz Luiz Antonio Pacheco , Viana Willian Carboni
Published: July 2023

Trazemos uma reflexão da materialidade como uma categoria que expressa e manifesta a condição fundamental dos seres humanos. Na nossa visão, as realizações da humanidade sempre foram intermediadas pelas coisas. Cada vez mais nos relacionamos por meio delas, devido à nossa capacidade de acumular conhecimento e convergir pensamentos em ações. As coisas se misturam ao nosso coletivo por meio das mais variadas formas (em casa, no trabalho, num museu etc.). Assim, apresentaremos uma breve discussão sobre a marginalização de estudos que enfocam a materialidade, nos quais geralmente são empregadas matrizes ontológicas convencionais que não conectam a cultura material à vida social. O texto oferece uma visão provocativa quanto à importância da materialidade e sobre a necessidade de abordagens que integrem essa dimensão em análises sociais mais amplas
REFLEXÕES SOBRE TEORIAS EPISTEMOLÓGICAS DO CONHECIMENTO QUE INFLUENCIAM O MULTICULTURALISMO
Authors: Bulhões Carlos Gabriel Araújo , Darsie Marta Maria Pontin , Leão Marcelo Franco
Published: July 2023

Com a globalização o fluxo migratório permitiu a coexistência entre diversas culturas, a qual resultou em um multiculturalismo social presente nas sociedades. Este texto teve como objetivo refletir sobre quais as teorias epistemológicas que se relacionam/influenciam na interculturalidade/ multiculturalismo presente nas sociedades em dias atuais. Configura-se como uma pesquisa bibliográfica, descritiva e exploratória, de abordagem qualitativa, cuja realização ocorreu no primeiro semestre de 2023. Foram realizadas reflexões sobre as nove categoriais epistemológicas (Empirismo; Racionalismo; Interacionista; Materialismo histórico; Tendência histórica; Teoria crítica; Pensamento complexo; Estruturalismo e Pós-estruturalismo), as quais possibilitaram identificar que a teoria epistemológica de Boaventura de Sousa Santos é a que mais se relaciona e/ou influencia no entendimento de multiculturalismo da sociedade contemporânea. A qual fundamenta-se numa visão descolonizada e fora do padrão eurocêntrico, buscando a construção de suas próprias epistemes.
O relato da construção social da pesquisa segundo a teoria da subjetividade
Authors: Bonato Fernanda Rafaela Cabral , Mussi Adriane , Baccarim Roberta Cristina Gobbi , Ferrarini Norma da Luz , Pellizzer Camila Marina Nery , Genez Luiza Ferrario , Gund Bruna
Published: July 2023

No processo de uma pesquisa científica em desenvolvimento, foi elaborado um cenário social da pesquisa que, entre os meses de março a abril de 2023, compartilhou informações sobre sexualidade feminina, saúde sexual e disfunções sexuais femininas em três plataformas digitais: Instagram, WhatsApp e E-mail, cujo objetivo foi o de alcançar e envolver possíveis participantes voluntárias para o estudo. Mulheres que se interessaram pelo tema e desejavam participar desta pesquisa preencheram um formulário disponibilizado nessas mesmas plataformas. Durante o período citado, foram obtidas 301 respostas ao formulário, das quais 148 demonstram interesse em participar do grupo psicoterapêutico online e 92 se enquadravam nos critérios da amostra. Destas 92 mulheres, 12 foram sorteadas por meio de técnica randomizada para participar da intervenção psicoterapêutica online. As informações disponibilizadas nas redes sociais quando da divulgação do formulário tinham o propósito de formar o cenário social de pesquisa, etapa essencial, uma vez que não bastava o mero preenchimento de informações no questionário, era preciso que a voluntária reconhecesse a presença de necessidades pessoais que a levassem a se interessar pelo grupo psicoterapêutico; necessidades essas que são elaboradas no próprio espaço da pesquisa, ou seja, no grupo psicoterapêutico.
Utilização de Role-Playing Game e discurso do sujeito coletivo no contexto de recursos hídricos para análise das estratégias dos jogadores
Authors: Born Míriam Blank , Mota Fernanda Pinto , De Aguiar Marilton Sanchotene , Adamatti Diana Francisca
Published: July 2023

Este estudo apresenta uma análise das estratégias utilizadas pelos jogadores de um RPG (Role-Playing Game) no contexto de recursos hídricos. Os RPGs são amplamente utilizados em várias áreas porque os indivíduos têm estratégias que se aproximam da realidade. No contexto da Educação Ambiental, o RPG ajuda no processo de compreensão do problema e como cada jogador pensa, analisa e observa uma situação de sua perspectiva e, assim, pode elaborar estratégias que considera relevantes para seu papel no jogo. A principal contribuição deste trabalho é um estudo empírico e qualitativo sobre a motivação dos indivíduos e como eles elaboraram suas estratégias. Como resultados, apresentamos a análise dos hábitos dos jogadores por meio de uma entrevista semiestruturada, a qual resultou em um conjunto de discursos, baseados na técnica do Discurso do Sujeito Coletivo (DSC). Assim, podemos concluir que os jogos, principalmente o RPG, pode ser uma ferramenta de auxílio no processo de aprendizagem ao permitir que situações do mundo real sejam experienciadas.
The Missing Piece to the Crisis Management Puzzle: Making the Best Decision
Authors: Kirschenbaum Alan (Avi) , Rapaport Carmit , Sagi Dotan , Zfaz Chelsea
Published: July 2023

The field of emergency preparedness and response has been driven recently by training efforts utilizing software based technology to mitigate and respond to potential and/or actual crisis situations. Yet, despite this effort, numerous research findings highlight the failures of both disaster and emergency agencies as well as private sector organizations in dealing with both major disruptions as well as local emergencies. We argue that a critical missing piece to rectify such failures, particularly in the training process, can be attained by refocusing on organizational processes toward preparedness/response with greater attention being paid to the context of how decisions are actually made and who makes them.

This critical missing element in preparation/response will be addressed here by laying out how data analytics associated with real-time behavioral decisions during an earthquake simulation can be utilized in optimizing the decision making process. This will provide a window into why protocols are not adhered to or how informal social networks within organizations are critical elements affecting decisions. To delve into this organizational reality, an emphasis will be put on not only the human factor in decision making but the organizational context within which interaction among and between employees takes place that affect how and what decisions are made.
How China’s “ Trade Not Aid ” Strategy Became Construed As Charitable Help : Deconstructing the “ Touching ” Idyll of Li Li’s Investment in Africa
Authors: Philip Hsiaopong Liu
Published: July 2023

In recent years, China has increased investments in Africa and its “Trade Not Aid” model appears to be the best delivery of sustainable assistance. By reviewing the history of Chinese aid to Africa, examining race-relations literature, and deconstructing contemporary models of aid, the author argues that, at least in terms of agricultural endeavors, China’s current approach resembles the colonialism that it once sought to disassemble.
Editorial: Setting Standards, Shifting Paradigms
Authors: Marsden Jane
Published: July 2023

In arguably a watershed year for counselling, psychotherapy, and Indigenous healing practices in Australia, this issue of the Psychotherapy and Counselling Journal of Australia (PACJA) is the first since it moved to the Scholastica platform. The move is helping PACJA meet international standards for peer-reviewed journals, in terms of discoverability, design, device-friendly pages, and other features. It comes at a time when the Australian Government has announced funding for the development of national standards for psychotherapists and counsellors, and for two independent peak bodies representing people who live with mental ill health and their carers and kin. This editorial details the articles in Volume 11 (1) of PACJA which emphasise the paradigm shifts accompanying these announcements.
Limites e Possibilidades da Adoção de Crianças e Adolescentes por Pessoas Idosas
Authors: Prado Janice Maria do
Published: July 2023

Propôs-se, com o presente artigo, analisar, a partir da revisão bibliográfica, os aspectos históricos, jurídicos e sociais da adoção de crianças e adolescentes por pessoas idosas. Utilizou-se a revisão narrativa de literatura, cuja pesquisa bibliográfica ocorreu nos meses de janeiro a abril de 2019, por meio da base de dados do Repositório Institucional da Universidade do Estado de São Paulo (UNESP), Biblioteca Digital da Pontifícia Universidade Católica (PUC) e nas plataformas Scientific Eletronic Library Online (Scielo) e Google Scholar. Verificou-se, com este estudo, que a família, a velhice e o instituto da adoção sofreram mudanças com o decorrer dos tempos e de acordo com a sociedade em que estavam inseridos. Concluiu-se que, na legislação brasileira, não existe impedimentos para que as pessoas idosas efetuem adoção de crianças e adolescentes, contudo, no imaginário social, persiste a associação do idoso ao exercício da avosidade, e não da maternidade ou paternidade.
Implementation of a Prevention Bundle to Decrease Rates of Staphylococcus aureus Surgical Site Infection at 11 Veterans Affairs Hospitals
Authors: Suzuki Hiroyuki , Perencevich Eli N. , Hockett Sherlock Stacey , Clore Gosia S. , O’Shea Amy M. J. , Forrest Graeme N. , Pfeiffer Christopher D. , Safdar Nasia , Crnich Christopher , Gupta Kalpana , Strymish Judith , Lira Gio Baracco , Bradley Suzanne , Cadena-Zuluaga Jose , Rubin Michael , Bittner Marvin , Morgan Daniel , DeVries Aaron , Miell Kelly , Alexander Bruce , Schweizer Marin L.
Published: July 2023

Importance

While current evidence has demonstrated a surgical site infection (SSI) prevention bundle consisting of preoperative Staphylococcus aureus screening, nasal and skin decolonization, and use of appropriate perioperative antibiotic based on screening results can decrease rates of SSI caused by S aureus, it is well known that interventions may need to be modified to address facility-level factors.

Objective

To assess the association between implementation of an SSI prevention bundle allowing for facility discretion regarding specific component interventions and S aureus deep incisional or organ space SSI rates.

Design, Setting, and Participants

This quality improvement study was conducted among all patients who underwent coronary artery bypass grafting, cardiac valve replacement, or total joint arthroplasty (TJA) at 11 Veterans Administration hospitals. Implementation of the bundle was on a rolling basis with the earliest implementation occurring in April 2012 and the latest implementation occurring in July 2017. Data were collected from January 2007 to March 2018 and analyzed from October 2020 to June 2023.

Interventions

Nasal screening for S aureus; nasal decolonization of S aureus carriers; chlorhexidine bathing; and appropriate perioperative antibiotic prophylaxis according to S aureus carrier status. Facility discretion regarding how to implement the bundle components was allowed.

Main Outcomes and Measures

The primary outcome was deep incisional or organ space SSI caused by S aureus. Multivariable logistic regression with generalized estimating equation (GEE) and interrupted time-series (ITS) models were used to compare SSI rates between preintervention and postintervention periods.

Results

Among 6696 cardiac surgical procedures and 16 309 TJAs, 95 S aureus deep incisional or organ space SSIs were detected (25 after cardiac operations and 70 after TJAs). While the GEE model suggested a significant association between the intervention and decreased SSI rates after TJAs (adjusted odds ratio, 0.55; 95% CI, 0.31-0.98), there was not a significant association when an ITS model was used (adjusted incidence rate ratio, 0.88; 95% CI, 0.32-2.39). No significant associations after cardiac operations were found.

Conclusions and Relevance

Although this quality improvement study suggests an association between implementation of an SSI prevention bundle and decreased S aureus deep incisional or organ space SSI rates after TJAs, it was underpowered to see a significant difference when accounting for changes over time.
Purtscher-Like Retinopathy Associated With Atypical Hemolytic Uremic Syndrome
Authors: Cheng Shi-yu , Chen You-xin
Published: July 2023

This case report discusses a diagnosis of atypical hemolytic uremic syndrome in a woman aged 38 years who presented with progressively blurry vision in both eyes over a period of 10 days.
Experimental Quantification of Halogen⋅⋅⋅Arene van der Waals Contacts
Authors: West Andrew M. L. , Dominelli‐Whiteley Nicholas , Smolyar Ivan V. , Nichol Gary S. , Cockroft Scott L.
Published: July 2023

Crystallographic and computational studies suggest the occurrence of favourable interactions between polarizable arenes and halogen atoms. However, the systematic experimental quantification of halogen⋅⋅⋅arene interactions in solution has been hindered by the large variance in the steric demands of the halogens. Here we have synthesized molecular balances to quantify halogen⋅⋅⋅arene contacts in 17 solvents and solvent mixtures using 1H NMR spectroscopy. Calculations indicate that favourable halogen⋅⋅⋅arene interactions arise from London dispersion in the gas phase. In contrast, comparison of our experimental measurements with partitioned SAPT0 energies indicate that dispersion is sufficiently attenuated by the solvent that the halogen⋅⋅⋅arene interaction trend was instead aligned with increasing exchange repulsion as the halogen increased in size (ΔGX⋅⋅⋅Ph=0 to +1.5 kJ mol−1). Halogen⋅⋅⋅arene contacts were slightly less disfavoured in solvents with higher solvophobicities and lower polarizabilities, but strikingly, were always less favoured than CH3⋅⋅⋅arene contacts (ΔGMe⋅⋅⋅Ph=0 to −1.4 kJ mol−1).
Atomically Precise Copper Nanoclusters for Highly Efficient Electroreduction of CO2 towards Hydrocarbons via Breaking the Coordination Symmetry of Cu Site
Authors: Wu Qiu‐Jin , Si Duan‐Hui , Sun Pan‐Pan , Dong Yu‐Liang , Zheng Song , Chen Qian , Ye Shi‐Hua , Sun Di , Cao Rong , Huang Yuan‐Biao
Published: July 2023

We propose an effective highest occupied d‐orbital modulation strategy engendered by breaking the coordination symmetry of sites in the atomically precise Cu nanocluster (NC) to switch the product of CO2 electroreduction from HCOOH/CO to higher‐valued hydrocarbons. An atomically well‐defined Cu6 NC with symmetry‐broken Cu−S2N1 active sites (named Cu6(MBD)6, MBD=2‐mercaptobenzimidazole) was designed and synthesized by a judicious choice of ligand containing both S and N coordination atoms. Different from the previously reported high HCOOH selectivity of Cu NCs with Cu−S3 sites, the Cu6(MBD)6 with Cu−S2N1 coordination structure shows a high Faradaic efficiency toward hydrocarbons of 65.5 % at −1.4 V versus the reversible hydrogen electrode (including 42.5 % CH4 and 23 % C2H4), with the hydrocarbons partial current density of −183.4 mA cm−2. Theoretical calculations reveal that the symmetry‐broken Cu−S2N1 sites can rearrange the Cu 3d orbitals with
as the highest occupied d‐orbital, thus favoring the generation of key intermediate *COOH instead of *OCHO to favor *CO formation, followed by hydrogenation and/or C−C coupling to produce hydrocarbons. This is the first attempt to regulate the coordination mode of Cu atom in Cu NCs for hydrocarbons generation, and provides new inspiration for designing atomically precise NCs for efficient CO2RR towards highly‐valued products.
Stimuli‐Responsive PROTACs for Controlled Protein Degradation
Authors: An Keli , Deng Xuqian , Chi Hongli , Zhang Yuchao , Li Yan , Cheng Ming , Ni Zhigang , Yang Zhi , Wang Chao , Chen Jinling , Bai Jianbo , Ran Chunyan , Wei Yong , Li Juan , Zhang Penghui , Xu Feng , Tan Weihong
Published: July 2023

Proteolysis Targeting Chimeras (PROTACs) represent a promising therapeutic modality to address undruggable and resistant issues in drug discovery. However, potential on‐target toxicity remains clinically challenging. We developed a generalized caging strategy to synthesize a series of stimuli‐responsive PROTACs (sr‐PROTACs) with diverse molecular blocks bearing robust and cleavable linkers, presenting “turn on” features in manipulating protein degradation. By leveraging pathological cues, such as elevated ROS, phosphatase, H2S, or hypoxia, and external triggers, such as ultraviolet light, X‐Ray, or bioorthogonal reagents, we achieved site‐specific activation and traceless release of original PROTACs through de‐caging and subsequent self‐immolative cleavage, realizing selective uptake and controlled protein degradation in vitro. An in vivo study revealed that two sr‐PROTACs with phosphate‐ and fluorine‐containing cages exhibited high solubility and long plasma exposure, which were specifically activated by tumor overexpressing phosphatase or low dosage of X‐Ray irradiation in situ, leading to efficient protein degradation and potent tumor remission. With more reactive biomarkers to be screened from clinical practice, our caging library could provide a general tool to design activatable PROTACs, prodrugs, antibody‐drug conjugates, and smart biomaterials for personalized treatment, tissue engineering or regenerative medicine.
Sensors and chemometrics in downstream processing
Authors: Dürauer Astrid , Jungbauer Alois , Scharl Theresa
Published: July 2023

The biopharmaceutical industry is still running in batch mode, mostly because it is highly regulated. In the past, sensors were not readily available and in‐process control was mainly executed offline. The most important product parameters are quantity, purity, and potency, in addition to adventitious agents and bioburden. New concepts using disposable single‐use technologies and integrated bioprocessing for manufacturing will dominate the future of bioprocessing. To ensure the quality of pharmaceuticals, initiatives such as Process Analytical Technologies, Quality by Design, and Continuous Integrated Manufacturing have been established. The aim is that these initiatives, together with technology development, will pave the way for process automation and autonomous bioprocessing without any human intervention. Then, real‐time release would be realized, leading to a highly predictive and robust biomanufacturing system. The steps toward such automated and autonomous bioprocessing are reviewed in the context of monitoring and control. It is possible to integrate real‐time monitoring gradually, and it should be considered from a soft sensor perspective. This concept has already been successfully implemented in other industries and requires relatively simple model training and the use of established statistical tools, such as multivariate statistics or neural networks. This review describes a scenario for integrating soft sensors and predictive chemometrics into modern process control. This is exemplified by selective downstream processing steps, such as chromatography and membrane filtration, the most common unit operations for separation of biopharmaceuticals.
Architecture learning environments: Pedagogy and space in the Universitat Politècnica de Catalunya's Sant Cugat Campus
Authors: Moreno Joan , Franquesa Jordi
Published: July 2023

The qualitative improvement of learning spaces in higher education has often been linked to the technicalization of classrooms, and to the dissolution of the physical and temporal framework of teaching. The main objective of this research was to examine the relationship between learning and space, beyond its formal and functional values, and how this relationship contributes to promoting an efficient, cohesive educational community that strengthens links with the society that it aspires to serve. Methodologically, a quantitative approach to the design of learning spaces is proposed in relation to three aspects: formal diversity, functional flexibility, and sociability of the university community. The proposed methodology was applied to the Universitat Politècnica de Catalunya's Sant Cugat Campus, which is recognized for the innovative nature of its pedagogical model, based on project‐based learning, and the adaptation of learning spaces to educational projects. With an educational model that tends to the spatial–temporal dissolution of learning and university spaces designed under the principles of form and function, improvement in the quality of learning is related to the improvement and quality of learning spaces using the principles of functional flexibility, spatial diversity, and sociability.
Significance of cell culture phases for utilizing 3D cultures of A549 cells for in vitro studies
Authors: N.G. Swethaa , Ravi Maddaly
Published: July 2023

Three‐dimensional (3D) culture systems of human cancer cell lines have become popular experimental models for a variety of applications including drug screening. It is understood that the 2D and 3D cultures of the same cell line behave differently in several aspects. One such difference is in the duration of cell culture phases (the lag, log, plateau and the decline stages). We obtained 3D cultures of A549 cells on agarose hydrogels. We observed and compared the morphological differences in the progression of 2D and 3D cultures of A549 cells in a time‐dependent manner. The morphological features along with the cell counts and viabilities obtained for the 2D and 3D cultures at different time intervals clearly indicate that the cell culture phases occurred as more extended one for the 3D cultures compared to that of the 2D counterparts. The plateau stage for the 2D and 3D cultures occurred at 48 and 69 h, respectively. Such cell culture phase durations can be different for different cell lines as a function of their doubling times. We propose that the cell culture phase durations for any cell line should be first established before using them for drug testing or for studies involving toxicity to obtain useful results from 3D cell cultures. Also, we propose that the late‐exponential (lag) phase of 3D cultures of cancer cell lines is the most ideal one for drug testing owing to the various optimal features of the aggregates in this cell culture phase.
Prognostic impact of coronary lesions and its revascularization in a 5‐year follow‐up after the TAVI procedure
Authors: Vázquez Domingo José López , López Guillermo Aldama , Guzmán Martin Quintas , Cancelo Ariana Varela , Leal Fernando Rebollal , Rios Xacobe Flores , Esteban Pablo Piñón , Fernandez Jorge Salgado , Santos Ramón Calviño , Rodriguez José Manuel Vázquez
Published: July 2023

Background

Coronary artery disease (CAD) is a common finding in patients undergoing transcatheter aortic valve implantation (TAVI). However, its prognostic significance and its management remains controversial.

Aims

This study sought to determine whether the presence of CAD, its complexity, and angiography‐guided percutaneous coronary intervention (PCI) are associated with outcomes after TAVI.

Methods

All patients undergoing TAVI at a tertiary referral center between 2008 and 2018 were included in a prospective observational study. Baseline SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score (SS) and a residual SS after PCI were calculated. The endpoints on the 5 year follow‐up were all‐cause mortality and a composite of mayor cardiovascular adverse events (MACE).

Results

In 379 patients, the presence of CAD and its complexity were not significantly associated with worse 5‐year survival after TAVI, with a mortality for SS0 of 45%; for SS 1–22 of 36.5% (HR 0.77; 95% CI 0.53–1.11, p = 0.15) and for SS > 22 of 42.1% (HR 1.24; 95% CI 0.59–2.63, p = 0.57). Regarding the combined event of MACE, there were also no statistically significant differences between patients with CAD and without CAD (56.8% in patients without CAD and 54.9% in patients with CAD; HR 1.06; 95% CI 0.79–1.43, p = 0.7). Angiography‐guided PCI or completeness of revascularization was not associated with different outcomes.

Conclusions

In the present analysis, neither the presence nor the extent of CAD, nor the degree of revascularization, was associated with a prognostic impact in patients undergoing TAVI at 5‐year follow‐up.
“CHIP‐ping” away at the definition of PCI “complexity” and “risk”
Authors: Chaus Adib , Uretsky Barry F.
Published: July 2023

Key Points

“Complex” and “High‐Risk” percutaneous coronary interventions remains a nebulous term.

This study shows poor inter‐rate agreement among EAPCI interventionalists in defining complexity and predicting risk of the procedure.

If we are able to appropriately to define the complexity and level of risk, we can potentially be better at assessing risk in the future.
Bottom‐up Synthesis of Nanosheets at Various Interfaces
Authors: Sasaki Koki , Uchida Yoshiaki , Nishiyama Norikazu
Published: July 2023

Nanostructured materials with high aspect ratios have been widely studied for their unique properties. In particular, nanosheets have safety, dispersibility, and nanosized effects, and nanosheets with exceptionally small thicknesses exhibit unique properties. For non‐exfoliable materials, the bottom‐up nanosheet growth using various interfaces as templates have been investigated. This review article presents the synthesis of nanosheets at the interfaces and layered structure; it explains the features of each interface type, its advantages, and its uniqueness. The interfaces work as templates for nanosheet synthesis. We can easily use the liquid‐liquid and gas‐liquid interfaces as the templates; however, the thickness of nanosheets usually becomes thick because it allows materials to grow in thickness. The solid‐gas and solid‐liquid interfaces can prevent nanosheets from growing in thickness. However, the removal of template solids is required after the synthesis. The layered structures of various materials provide two‐dimensional reaction fields between the layers. These methods have high versatility, and the nanosheets synthesized by these methods are thin. Finally, this review examines the key challenges and opportunities associated with scalable nanosheet synthesis methods for industrial production.
Fusobacterium nucleatum infection activates the noncanonical inflammasome and exacerbates inflammatory response in DSS‐induced colitis
Authors: Boonyaleka Kotchakorn , Okano Tokuju , Iida Tamako , Leewananthawet Anongwee , Sasai Miwa , Yamamoto Masahiro , Ashida Hiroshi , Suzuki Toshihiko
Published: July 2023

Caspase activation results in pyroptosis, an inflammatory cell death that contributes to several inflammatory diseases by releasing inflammatory cytokines and cellular contents. Fusobacterium nucleatum is a periodontal pathogen frequently detected in human cancer and inflammatory bowel diseases. Studies have reported that F. nucleatum infection leads to NLRP3 activation and pyroptosis, but the precise activation process and disease association remain poorly understood. This study demonstrated that F. nucleatum infection exacerbates acute colitis in mice and activates pyroptosis through caspase‐11‐mediated gasdermin D cleavage in macrophages. Furthermore, F. nucleatum infection in colitis mice induces the enhancement of IL‐1⍺ secretion from the colon, affecting weight loss and severe disease activities. Neutralization of IL‐1⍺ protects F. nucleatum infected mice from severe colitis. Therefore, F. nucleatum infection facilitates inflammation in acute colitis with IL‐1⍺ from colon tissue by activating noncanonical inflammasome through gasdermin D cleavage.
Syntheses, Characterization, and DNA Binding Studies of a Series of Copper(II), Nickel(II), Platinum(II) and Zinc(II) Complexes Derived from Schiff Base Ligands
Authors: Iannace Valentina , Sabaté Ferran , Bartlett Molly , Berrones Reyes Jessica , Lázaro Ariadna , Fantoni Alessia , Vilar Ramon , Rodríguez Laura , Dalla Cort Antonella
Published: July 2023

Three series of metal salophen complexes derived from Zn2+, Cu2+, Pt2+ and Ni2+ have been synthesized and their interaction with quadruplex DNA has been evaluated. The compounds differ on the number of ethyl piperidine substituents. They have been characterized by 1H NMR, IR and UV‐visible spectroscopies and by HR‐mass spectrometry. Their luminescent properties have been also evaluated and we can observe that, as expected, Zn2+ and Pt2+ complexes are those displaying more interesting luminescence with an emission band red‐shifted with respect to the corresponding uncoordinated ligand. DNA interactions with G4 and duplex DNA were evaluated by FRET melting assays (for the Zn2+, Cu2+ and Ni2+ complexes) and by emission titrations (for one Pt2+ complex) which indicated that the disubstituted compounds 2‐Ni and 2‐Pt are the only ones that display good affinity for G4 DNA structures.
Catalytic Potential of Pyrazolone Based Dioxidomolybdenum(VI) Complexes for Multicomponent Biginelli Reactions, Epoxidation of Olefins and Oxidative Bromination of Phenol Derivatives
Authors: Maurya Mannar R. , Singh Devesh , Bisht Rahul , Avecilla Fernando , Sharma Akhilesh , Gupta Puneet
Published: July 2023

Three different types of dioxidomolybdenum(VI) complexes of 4‐acetyl‐3‐methyl‐1‐phenyl‐5‐pyrazolone (Hmp, I)), 3‐methyl‐1‐phenyl‐4‐propionyl‐5‐pyrazolone (Hpp, II), 4‐butyryl‐3‐methyl‐1‐phenyl‐5‐pyrazolone (Hbutp, III), and 4‐isobutyryl‐3‐methyl‐1‐phenyl‐5‐pyrazolone (isobutp, IV) have been isolated and characterized by various spectroscopic (FT‐IR, UV/Vis, 1H and 13C NMR) techniques, thermal analysis and single crystal X‐ray analysis. These complexes adopt a distorted six‐coordinate octahedral geometry where ligands act as bidentate, coordinating through the two O atoms. These complexes have been used as catalysts to explore a single pot multicomponent (benzaldehyde or its derivatives, urea/thiourea and ethyl acetoacetate/phenyl acetoacatate) Biginelli reaction producing biologically active 3,4‐dihydropyrimidin‐2‐(1H)‐one and 3,4‐dihydropyrimidin‐2‐(1H)‐thione based biomolecules under solvent‐free conditions. Presence of H2O2 improves the yield of dihydropyrimidin‐2‐(1H)‐one but it acts as poison for the later molecule. Epoxidation of internal and terminal alkenes mainly resulted in the formation of the corresponding epoxide. The catalytic oxidative bromination of thymol, a reaction facilitated by vanadium dependent haloperoxidases, resulted in the formation of three product namely 2‐bromothymol, 4‐bromothymol and 2,4‐bromothymol. Other phenol derivatives have also been brominated effectively.
Screening lactic acid bacteria and yeast strains for soybean paste fermentation in northeast of China
Authors: Li Siyi , Guo Linjie , Gu Jinhong , Mu Guangqing , Tuo Yanfeng
Published: July 2023

Soybean paste was a traditional fermented product in northeast China, mainly fermented by molds, yeast, Bacillus, and lactic acid bacteria. In this study, the safety and fermentation ability of lactic acid bacteria and yeast strains isolated from traditional soybean paste in northeast China were evaluated, and the dynamic changes of biogenic amines, aflatoxin, total acids, amino acid nitrogen, and volatile compounds were investigated during the fermentation of the traditional soybean paste. Among the tested strains, Lactiplantibacillus plantarum DPUL‐J8 could decompose putrescine by 100%, and no biogenic amine was produced by Pichia kudriavzevii DPUY‐J8. Lactiplantibacillus plantarum DPUL‐J8 and P. kudriavzevii DPUY‐J8 with strong biogenic amine degrading capacities were inoculated into the soybean paste. After 30 days of fermentation, the content of biogenic amines and aflatoxin in the fermented soybean paste declined by more than 60% and 50%, respectively. At the same time, compared with the control group without inoculation, the contents of total acid (1.29 ± 0.05 g/100 g), amino acid nitrogen (0.82 ± 0.01 g/100 g), and volatile compounds in soybean paste fermented by L. plantarum DPUL‐J8 and P. kudriavzevii DPUY‐J8 were significantly increased, which had a good flavor. These results indicated that the use of L. plantarum DPUL‐J8 and P. kudriavzevii DPUY‐J8 as starter cultures for soybean paste might be a good strategy to improve the safety and flavor of traditional Chinese soybean paste.
Oral azvudine for mild‐to‐moderate COVID‐19 in high risk, nonhospitalized adults: Results of a real‐world study
Authors: Yang Hui , Wang Zhaojian , Jiang Chunguo , Zhang Yi , Zhang Ying , Xu Man , Zhang Yi , Wang Yushu , Liu Xuefeng , An Zhuoling , Tong Zhaohui
Published: July 2023

Azvudine is recommended by Chinese health authorities for COVID‐19 treatment but has not been tested in real‐world clinical studies. This study aimed to evaluate the real‐world effectiveness of Azvudine among COVID‐19 nonhospitalized patients. This was a retrospective cohort study, looking at nonhospitalized patients who tested positive for SARS‐CoV‐2. Patients admitted between December 19, 2022 and January 5, 2023 were included. Those who received Azvudine treatment were in the Azvudine group, while those who received supportive treatment were the control group. The primary outcome was the disease progression rate by Day 28. Secondary outcomes were individual disease progression outcomes (death or COVID‐19‐related hospitalization) and duration of fever. The safety outcomes were assessed based on adverse events (AEs) overall, as well as AEs that were considered to be related to the drug. A total of 804 patients with high risk for progression were enrolled in our study. Among them, 317 (39.43%) received treatment with Azvudine. Our study found that Azvudine could reduce the rate of disease progression, as well as rate of COVID‐19‐related hospitalization in patients comparing the control group. Furthermore, if taken within 3 days of the onset of symptoms, it could also shorten the duration of fever. Despite a higher incidence of drug‐related AEs compared to supportive treatment, the majority of these were mild. Azvudine has been found to be effective in reducing the rate of disease progression of COVID‐19, albeit with a slight increase in AEs.
Strategies for Achieving Oxygen Tolerance in Reversible Addition–Fragmentation Chain Transfer Polymerization
Authors: Ng Gervase , Prescott Stuart W. , Postma Almar , Moad Graeme , Hawker Craig J. , Boyer Cyrille
Published: July 2023

Reversible addition–fragmentation chain transfer polymerization (RAFT) is a popular method for the synthesis of well‐defined macromolecules, but its sensitivity to oxygen is a major limitation for many industrial applications. Recent research has focused on developing strategies to confer oxygen tolerance onto RAFT polymerization, eliminating the need for deoxygenation steps and allowing for simpler reaction conditions. This minireview highlights several promising approaches to achieve oxygen tolerance in RAFT polymerization, including enzyme‐mediated, alkylborane‐initiated, and photomediated methods. The potential applications of oxygen‐tolerant RAFT polymerization are also discussed, demonstrating the promise for significant advances in large‐scale industrial polymer synthesis.
Synthesis of Novel Polymers via ROMP of Benzyne‐Derived Monomers and Their NMR Spectroscopic Properties
Authors: Enríquez‐Figueroa René Alberto , Pineda‐Contreras Armando , Vázquez‐Vuelvas Oscar F. , González‐González Juan‐Saulo , Fomine Serguei
Published: July 2023

Dehydrohalogenation of 1,4‐dihalobenzenes and 1,2,4‐trichlorobenzene is performed using n‐BuLi to form benzynes. These benzynes are used as dienophiles in a Diels–Alder reaction with the dienes furan and 2,5‐dimethylfuran to prepare new benzonorbornadiene derivatives. The cycloadducts of furan are polymerized by a ring‐opening metathesis reaction using a Hoveyda–Grubbs ruthenium catalyst. The polymers are characterized by 1H NMR (nuclear magnetic resonance), and unambiguous proton chemical shift assignments are based on the multiplicity pattern of proton resonances. This is confirmed by 2D NMR data from HSQC(Heteronuclear Single Quantum Coherence) and COSY (Correlation Spectroscopy) spectra. The polybenzonorbornadienes have both cis and trans conformation in their chemical structure. The trans conformation is qualitatively in greater proportion observed at 1H NMR experiments. These materials may have syndiotactic microstructure by the lack of correlations in COSY.
Intermediate‐term oncological and functional outcomes of salvage cryotherapy for the management of prostate cancer recurrence after primary brachytherapy versus primary cryotherapy: A propensity score‐matched analysis
Authors: Deivasigamani Sriram , Orabi Hazem , El‐Shafei Ahmed , Adams Eric S. , Kotamarti Srinath , Aminsharifi Ali , Davis Leah , Wu Yuan , J. Stephen Jones , Polascik Thomas J.
Published: July 2023

Background

Salvage cryotherapy (SCT) is widely used to treat prostate cancer (PCa) recurrence after radiotherapy (RT). We studied the intermediate oncological and functional outcomes of patients who underwent SCT following cryotherapy (CRYO‐SCT) recurrence and compare it to recurrence after brachytherapy (BT‐SCT).

Methods

An IRB‐approved retrospective cohort study utilizing patient data from the Cryo On‐Line Data Registry and the Duke PCa database between 1992 and 2016. Biochemical recurrence (BCR) using Phoenix criteria was the primary endpoint assessed at 2‐ and 5‐years post‐SCT. Secondary endpoints assessed functional outcomes including urinary continence, erectile function, and recto‐urethral fistula. Association between treatment and biochemical progression‐free survival was assessed using inverse probability weighted (IPTW) Cox proportional hazards regression. The differences in the secondary functional outcomes were assessed by Pearson's χ2 test or Fisher's exact test, corrected for IPTW.

Results

A total of 194 patients met inclusion criteria. The BCR rate for BT‐SCT and CRYO‐SCT was 23 (20.4%) and 17 (21%) at 2 years and 30 (26.5%) and 22 (27.2%) at 5 years according to Phoenix criteria. There was no statistical difference in 2 years (hazard ratio [HR] 0.9; 95% confidence interval [CI], 0.5–1.7, p = 0.7) or 5‐year BCR (HR: 0.86; 95% CI, 0.5‐1.5, p = 0.6) between the groups. The functional outcomes like urinary continence (p = 0.4), erectile function (p = 0.1), and recto‐urethral fistula (p = 0.3) were not statistically different.

Conclusion

CRYO‐SCT appears to be well tolerated, with comparable oncological and functional outcomes to patients failing primary BT. The findings also demonstrated that SCT can render a significant number of patients biochemically free of disease after initial CRYO with minimal morbidity. SCT is a viable treatment option to salvage local PCa recurrence following either BT or cryoablation failure.