bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of Human CD8+ T Cells with Nitroso Dapsone–Modified HLA-B*13:01–Binding Peptides
Authors: Almutairi Mubarak , Lister Adam , Zhao Qing , Line James , Adair Kareena , Tailor Arun , Waddington James , Clarke Elsie , Gardner Joshua , Thomson Paul , Harper Nicolas , Sun Yonghu , Sun Lele , Ostrov David A , Liu Hong , MacEwan David J , Pirmohamed Munir , Meng Xiaoli , Zhang Furen , Naisbitt Dean J 
Published: March 2023

Abstract
Previous studies have shown that cysteine-reactive drug metabolites bind covalently with protein to activate patient T cells. However, the nature of the antigenic determinants that interact with HLA and whether T cell stimulatory peptides contain the bound drug metabolite has not been defined. Because susceptibility to dapsone hypersensitivity is associated with the expression of HLA-B*13:01, we have designed and synthesized nitroso dapsone–modified, HLA-B*13:01 binding peptides and explored their immunogenicity using T cells from hypersensitive human patients. Cysteine-containing 9-mer peptides with high binding affinity to HLA-B*13:01 were designed (AQDCEAAAL [Pep1], AQDACEAAL [Pep2], and AQDAEACAL [Pep3]), and the cysteine residue was modified with nitroso dapsone. CD8+ T cell clones were generated and characterized in terms of phenotype, function, and cross-reactivity. Autologous APCs and C1R cells expressing HLA-B*13:01 were used to determine HLA restriction. Mass spectrometry confirmed that nitroso dapsone–peptides were modified at the appropriate site and were free of soluble dapsone and nitroso dapsone. APC HLA-B*13:01–restricted nitroso dapsone–modified Pep1- (n = 124) and Pep3-responsive (n = 48) CD8+ clones were generated. Clones proliferated and secreted effector molecules with graded concentrations of nitroso dapsone–modified Pep1 or Pep3. They also displayed reactivity against soluble nitroso dapsone, which forms adducts in situ, but not with the unmodified peptide or dapsone. Cross-reactivity was observed between nitroso dapsone–modified peptides with cysteine residues in different positions in the peptide sequence. These data characterize a drug metabolite hapten CD8+ T cell response in an HLA risk allele–restricted form of drug hypersensitivity and provide a framework for structural analysis of hapten HLA binding interactions.
NF-κB–Inducing Kinase Governs the Mitochondrial Respiratory Capacity, Differentiation, and Inflammatory Status of Innate Immune Cells
Authors: Keeney Justin N , Winters Ashley D , Sitcheran Raquel , West A Phillip 
Published: March 2023

Abstract
NF-κB–inducing kinase (NIK), which is essential for the activation of the noncanonical NF-κB pathway, regulates diverse processes in immunity, development, and disease. Although recent studies have elucidated important functions of NIK in adaptive immune cells and cancer cell metabolism, the role of NIK in metabolic-driven inflammatory responses in innate immune cells remains unclear. In this study, we demonstrate that murine NIK-deficient bone marrow–derived macrophages exhibit defects in mitochondrial-dependent metabolism and oxidative phosphorylation, which impair the acquisition of a prorepair, anti-inflammatory phenotype. Subsequently, NIK-deficient mice exhibit skewing of myeloid cells characterized by aberrant eosinophil, monocyte, and macrophage cell populations in the blood, bone marrow, and adipose tissue. Furthermore, NIK-deficient blood monocytes display hyperresponsiveness to bacterial LPS and elevated TNF-α production ex vivo. These findings suggest that NIK governs metabolic rewiring, which is critical for balancing proinflammatory and anti-inflammatory myeloid immune cell function. Overall, our work highlights a previously unrecognized role for NIK as a molecular rheostat that fine-tunes immunometabolism in innate immunity, and suggests that metabolic dysfunction may be an important driver of inflammatory diseases caused by aberrant NIK expression or activity.
C-Reactive Protein: The Most Familiar Stranger
Authors: Ji Shang-Rong , Zhang Shu-Hao , Chang Yue , Li Hai-Yun , Wang Ming-Yu , Lv Jian-Min , Zhu Li , Tang Patrick M K , Wu Yi 
Published: March 2023

Abstract
C-reactive protein (CRP) is a highly conserved pentraxin with pattern recognition receptor–like activities. However, despite being used widely as a clinical marker of inflammation, the in vivo functions of CRP and its roles in health and disease remain largely unestablished. This is, to certain extent, due to the drastically different expression patterns of CRP in mice and rats, raising concerns about whether the functions of CRP are essential and conserved across species and how these model animals should be manipulated to examine the in vivo actions of human CRP. In this review, we discuss recent advances highlighting the essential and conserved functions of CRP across species, and propose that appropriately designed animal models can be used to understand the origin-, conformation-, and localization-dependent actions of human CRP in vivo. The improved model design will contribute to establishing the pathophysiological roles of CRP and facilitate the development of novel CRP-targeting strategies.
Visual symptoms with Sofosbuvir in hepatitis C treatment — a case report from Pakistan
Authors: Hasnain Aliya , Shah Sabeen , Hampejskova Lindsay 
Published: March 2023

Hepatitis C virus infection is one of the main causes of chronic liver disease worldwide. The highly efficacious direct-acting antiviral (DAA) drugs licensed for therapy have revolutionised the treatment and are reported to have few side effects. Sofosbuvir is a pan-genotypic DAA that acts by inhibition of the hepatitis C NS5B polymerase. It has shown high efficacy in combination with several other drugs with low toxicity, a high resistance barrier, and minimal drug interactions with other hepatitis C DAA drugs. We describe a first of its kind case from Pakistan with visual disturbances caused by Sofosbuvir. A temporal relationship was observed between the treatment initiation and the onset of visual disturbances. The aim of this case report is to draw attention to the unanticipated side effects of this relatively new class of drug that have not been reported previously.
Keywords: Sofosbuvir, Hepatitis C, Colour vision, Pakistan.
Pharmacokinetics and bioavailability of tocotrienols in healthy human volunteers: a systematic review
Authors: Sharif Mahjabeen , Khan Dilshad  Ahmed , Farhat Kulsoom , Mudassar Noor  , Mohammad Asghar Khan  , Saima Rafique  
Published: March 2023

Objectives: To evaluate and compare the pharmacokinetic parameters, especially bioavailability, of annatto-based tocotrienol with palm tocotrienol-rich fraction in healthy human volunteers for better therapeutic outcome.
Method: The systematic review was conducted between April and August 2021 in accordance with the Preferred Reporting Items for Systematic Review and Meta Analysis guidelines, and comprised search on PubMed, Google Scholar, Pakmedinet and Google search engines for open-label or double-blind randomised controlled trials involving healthy human volunteers published till January 2021. Key words used included annatto-based tocotrienol, palm tocotrienol-rich fraction, absorption and bioavailability. Boolean operators were also used, like tocotrienol AND bioavailability, annatto tocotrienol AND pharmacokinetics.
Results: Of the 230 articles identified, 50(21.7%) articles met the eligibility criteria. Of them, 7(14%) were selected for data extraction and detailed analysis. Pharmacokinetic parameters of annatto-based tocotrienol were better than palm-derived tocotrienol. Oral administration of all the isomers of annatto-based tocotrienols resulted in dose-dependent increase in area under curve and plasma levels. Amongst all the isomers of annatto-based and palm-derived tocotrienol, delta isomer of annatto-based tocotrienol had the highest bioavailability with area under curve 7450±89 ng/ml, time to reach peak plasma levels 4 hours, maximum plasma concentration 1591±43 ng/nl and elimination half-life 2. 68 ±0.29 hrs. Pharmacokinetic parameters of delta isomer of annatto-based tocotrienol was greater than palm tocotrienol-rich fraction.
Conclusion: Bioavailability of annatto-based tocotrienol was better than that of palm-derived tocotrienol-rich fraction. Delta isomer of annatto-based tocotrienol had the highest bioavailability amongst all isomers of tocotrienol.
Upaya Meningkatkan Perilaku Disiplin Anak Usia Dini Melalui Parenting di TK Kuwaisyah
Authors: Suryani Ririn , Julaiha Juli , Pahira Nst Annisa , Simanjuntak Rahmayeni , Humairah Nst Rahma , Saputri Novia , Siregar Rini Lestari , Pasaribu Asriyani , Nuriyati Nuriyati , Andini Yuliana , Shofiah Mir-atun , Fauziah Sindi 
Published: March 2023

This research aims to improve the disciplined behavior of children aged 4-5 years through parenting at Kuwaisyah Kindergarten, Delitua Village, Kec. West Delitua, Kab. Deli Serdang, North Sumatra. The subjects in this study were young children 4-5 years old, namely group A in Kuwaisyah Kindergarten, Delitua Village, Kec. West Delitua, Kab. Deli Serdang, North Sumatra. The method used is a qualitative method with the aim of obtaining in-depth information through parenting activities. Informants are parents who have children and who provide care. The informants were divided into two parts, namely, only one parent who worked or both parents of the child worked. Furthermore, in collecting data using observations, interviews, observations, notes, and documentation (photos). The results of this study indicate that parenting activities can be used as an alternative in improving children's discipline.
Keywords:implementation, parenting, disciplined behavior of children aged 4-5 years
Impact of the Industrial Revolution on Family Structure in Nigeria
Authors: Ajabi Todabi 
Published: March 2023

Purpose: The study sought to analyze the impacts of industrial revolution on the family structure in Nigeria
Methodology: The study adopted a desktop methodology. Desk research refers to secondary data or that which can be collected without fieldwork. Desk research is basically involved in collecting data from existing resources hence it is often considered a low cost technique as compared to field research, as the main cost is involved in executive’s time, telephone charges and directories. Thus, the study relied on already published studies, reports and statistics. This secondary data was easily accessed through the online journals and library.
Findings: The results show that there has been a change of family structure since the pre industrialization era and the post industrialization era. The historical process of industrialization changed the ways in which families were structured and interacted. Family bonding are decreasing and divorce rate is increasing rapidly. These shift not only affected the roles of spouses and parents but also those of children. Industrialization changed gender roles and Enlightenment philosophies that inspired new ideals of equality, personal freedom, and individualism.
Unique Contribution to Theory, Practice and Policy: The modernization theory, Talcott Parsons’ theory and the classic sociological theory may be used to anchor future studies in the sociology sector. The study results will also benefit other stakeholders such as the policy makers as well as researchers and scholars from different parts of the world. The top management of both public and private industries in the country will also use the study findings to improve families and ensure high and stable performance in all their activities and programs. The study recommends that the adoption of effective social protection development policies in the family structure will help to improve efficiency in their major operations and activities.
Impact of Sensationalized Media Coverage and Perception on Current Events in Myanmar
Authors: CHI Win 
Published: March 2023

Purpose: The study sought to analyze the impacts of sensationalized media coverage and perception on current events in Myanmar
Methodology: The study adopted a desktop methodology. Desk research refers to secondary data or that which can be collected without fieldwork. Desk research is basically involved in collecting data from existing resources hence it is often considered a low cost technique as compared to field research, as the main cost is involved in executive’s time, telephone charges and directories. Thus, the study relied on already published studies, reports and statistics. This secondary data was easily accessed through the online journals and library.
Findings: The results show that showed that sensationalist television news tends to be more negatively evaluated than non-sensationalist news. In addition, critical views on arousing content appeared to be particularly visible among young and middle-aged adults. These findings suggest that the rise of sensationalist news could be an explanation of the declining trust in news media that is witnessed in a number of countries
Unique Contribution to Theory, Practice and Policy: The media logic theory and the agenda setting theory may be used to anchor future studies in the information sector. The study results will also benefit other stakeholders such as the policy makers as well as researchers and scholars from different parts of the world. The top management of media companies industries in the country will also use the study findings to improve social media coverage performance in all their activities and programs. The study recommends that the adoption of effective social protection development policies in the media will help to improve efficiency in their major operations and activities.
ÍNDICE DE DESENVOLVIMENTO SUSTENTÁVEL PARA MUNICÍPIOS: UMA ANÁLISE NA REGIÃO CANTUQUIRIGUAÇU -PR / SUSTAINABLE DEVELOPMENT INDEX FOR MUNICIPALITIES: AN ANALYSIS IN THE CANTUQUIRIGUAÇU/PR REGION IN BRAZIL
Authors: Kasper Karen Alice , Stoffel Janete 
Published: March 2023

Este trabalho tem como objetivo identificar e analisar o nível de desenvolvimento sustentável dos municípios que constituem a Região da Cantuquiriguaçu/PR. Para tal é utilizado o Índice de Desenvolvimento Sustentável para Municípios (IDSM). O indicador é calculado seguindo a metodologia de Martins e Cândido (2008). São efetuados os cálculos do índice para seis dimensões: social, demográfica, econômica, político-institucional, ambiental e cultural. São utilizadas sessenta e sete variáveis distribuídas nestas dimensões. Em cada dimensão os resultados são apresentados de forma individual para os vinte municípios e é calculada a média da região. Neste ínterim nas dimensões demográfica, econômica, político institucional, ambiental e cultural a média do IDSM para a região está no nível alerta. Apenas na dimensão social o índice é aceitável. Em consequência, a região apresenta um índice de sustentabilidade no nível alerta.

Abstract: This article aimed to identify and analyze the level of sustainable development of the municipalities comprising the Cantuquiriguaçu/PR Region. The Sustainable Development Index for Municipalities (SDIM) was used for this purpose. The index was calculated following the methodology of Martins and Cândido (2008). The calculations were performed for six dimensions: social, demographic, economic, political-institutional, environmental, and cultural. Sixty-seven variables distributed along these dimensions were used. In each dimension the results were presented individually for the twenty municipalities and the average for the region was calculated. Meanwhile, regarding the demographic, economic, political, institutional, environmental and cultural dimensions, the average SDIM for the region is at the alert level. Only in the social dimension is the index acceptable. Consequently, the region presents a sustainability index at the alert level.
MÔ TẢ SỰ HÀI LÒNG CỦA NGƯỜI THÂN CÓ TRẺ TỪ 4-8 TUỔI ĐƯỢC ĐIỀU TRỊ PHỤC HỒI THÂN RĂNG HÀM SỮA BẰNG CHỤP THÉP TẠI BỆNH VIỆN TRƯỜNG ĐẠI HỌC Y KHOA VINH NĂM 2022
Authors: Nguyễn Thị Hoa , Nguyễn Thị Cẩm Tú 
Published: March 2023

Trẻ em có số lần thay thế lại những miếng trám Amalgam lớn hoặc nhiều mặt là 2-4 lần trong năm và rất khó khăn phục hồi lại hình thể thân răng phù hợp với các vật liệu này. Đặc biệt là các răng đã điều trị tủy thì thường bị gãy vỡ sau đó mất sớm để lại nhiều hậu quả nghiêm trọng. Để giải quyết các vấn đề này, chụp thép đúc sẵn đã được sử dụng trong nha khoa phục hồi răng trẻ em. Nghiên cứu nhằm mục tiêu mô tả sự hài lòng của người thân có trẻ từ 4-8 tuổi được điều trị phục hồi thân răng hàm sữa bằng chụp thép tại bệnh viện Trường Đại học y khoa Vinh năm 2022. Nghiên cứu triển khai trên 13 người thân có bệnh nhân được chỉ định điều trị chụp thép. Kết quả cho thấy tỷ lệ hài lòng chung về sự thuận tiện 76,9%, chất lượng 84,6%, kiểm soát đau cho trẻ 92,3%, chi phí điều trị là 84,6%.
ỨNG DỤNG KỸ THUẬT SIÊU ÂM DOPPLER BẰNG MÁY USCOM ĐỂ THEO DÕI VÀ ĐIỀU CHỈNH HUYẾT ĐỘNG Ở BỆNH NHÂN NHIỄM KHUẨN NẶNG VÀ SỐC NHIỄM KHUẨN TẠI BỆNH VIỆN HỮU NGHỊ ĐA KHOA NGHỆ AN
Authors: Nguyễn Đức Phúc , Lê Anh Tuấn 
Published: March 2023

Mục tiêu: Ứng dụng kỹ thuật siêu âm Doppler bằng máy USCOM để theo dõi và điều chỉnh huyết động ở bệnh nhân nhiễm khuẩn nặng và sốc nhiễm khuẩn. Đối tượng và phương pháp: Nghiên cứu tiến cứu mô tả can thiệp 43 bệnh nhân được chẩn đoán nhiễm khuẩn nặng và sốc nhiễm khuẩn. Kết luận: Độ biến thiên thể tích nhát bóp SVV có vai trò đánh giá theo dõi và hướng dẫn bù dịch, sức cản mạch hệ thống SVRI có vai trò trong đánh giá theo dõi và hướng dẫn sủ dụng thuốc co mạch, sức co bóp cơ tim INO có vai trò trong đánh giá theo dõi và hướng dẫn sử dụng thuốc tăng co bóp cơ tim.
Variable effects of spatial resolution on modeling of nitrogen oxides
Authors: Li Chi , Martin Randall V. , Cohen Ronald C. , Bindle Liam , Zhang Dandan , Chatterjee Deepangsu , Weng Hongjian , Lin Jintai 
Published: March 2023

Abstract. The lifetime and concentration of nitrogen oxides (NOx) are susceptible to nonlinear production and loss and to the resolution of a chemical transport model (CTM). This is due to the strong spatial gradients of NOx and the dependence of its own chemical loss on such gradients. In this study, we use the GEOS-Chem CTM in its high-performance implementation (GCHP) to investigate NOx simulations over the eastern United States across a wide range of spatial model resolutions (six different horizontal grids from 13 to 181 km). Following increasing grid size, afternoon surface NOx mixing ratios over July 2015 generally decrease over the Great Lakes region (GL) and increase over the southern states of the US region (SS), yielding regional differences (181 km vs. 13 km) of −16 % (in the GL) to 7 % (in the SS); meanwhile, hydrogen oxide radicals (HOx) increase over both regions, consistent with their different chemical regimes (i.e., NOx-saturated in the GL and NOx-limited in the SS). Nighttime titration of ozone by surface nitric oxide (NO) was found to be more efficient at coarser resolutions, leading to longer NOx lifetimes and higher surface mixing ratios of nitrogen dioxide (NO2) over the GL in January 2015. The tropospheric NO2 column density at typical afternoon satellite overpass time has spatially more coherent negative biases (e.g., −8 % over the GL) at coarser resolutions in July, which reversed the positive biases of surface NOx over the SS. The reduced NOx aloft (>1 km altitude) at coarser resolutions was attributable to the enhanced HOx that intrudes into the upper troposphere. Application of coarse-resolution simulations for interpreting satellite NO2 columns will generally underestimate surface NO2 over the GL and overestimate surface NO2 over the SS in summer, but it will uniformly overestimate NOx emissions over both regions. This study significantly broadens understanding of factors contributing to NOx resolution effects and the role of fine-resolution data in accurately simulating and interpreting NOx and its relevance to air quality.
An evaluation of long-term physical and hydrochemical measurements at the Sylt Roads Marine Observatory (1973–2019), Wadden Sea, North Sea
Authors: Rick Johannes J. , Scharfe Mirco , Romanova Tatyana , van Beusekom Justus E. E. , Asmus Ragnhild , Asmus Harald , Mielck Finn , Kamp Anja , Sieger Rainer , Wiltshire Karen H. 
Published: March 2023

Abstract. The Sylt Roads pelagic time series covers physical and hydrochemical parameters at five neighboring stations in the Sylt–Rømø bight, Wadden Sea, North Sea. Since the beginning of the time series in 1973, sea surface temperature (SST), salinity, ammonium, nitrite, nitrate, and soluble reactive phosphorus (SRP) have been measured twice a week. The other parameters were introduced later (dissolved silicate (Si) since 1974, pH since 1979, dissolved organic nitrogen (DON) since 1996, dissolved organic phosphorus (DOP) since 2001, chlorophyll a since 1979, and suspended particulate matter (SPM) since 1975), and in the case of dissolved oxygen, were already discontinued (1979–1983). In the years 1977, 1978, and 1983, no sampling took place. Since the start of the continuous sampling in 1984, the sea surface temperature in the bight has risen by +1.11 ∘C, with the highest increases during the autumn months, while the pH and salinity decreased by 0.23 and 0.33 units, respectively. Summer and autumn salinities are generally significantly elevated compared to spring and winter conditions. Dissolved nutrients (ammonium, nitrite, nitrate, and SRP) have displayed periods of intense eutrophication (1973–1998) and de-eutrophication since 1999. Silicate has shown significantly higher winter levels since 1999. Interestingly, phytoplankton parameters did not mirror these large changes in nutrient concentrations, as a seasonal comparison of the two eutrophication periods showed no significant differences with regard to chlorophyll a. This phenomenon might be triggered by an important switch in nutrient limitation during the time series. With regard to nutrients, the phytoplankton was probably primarily limited by silicate until 1998, while, since 1999, the SRP limitation has become increasingly important. All data are available in Rick et al. (2017b–e, 2020a–o) from https://doi.org/10.1594/PANGAEA.150032, https://doi.org/10.1594/PANGAEA.873549, https://doi.org/10.1594/PANGAEA.873545, https://doi.org/10.1594/PANGAEA.873547, https://doi.org/10.1594/PANGAEA.918018, https://doi.org/10.1594/PANGAEA.918032, https://doi.org/10.1594/PANGAEA.918027, https://doi.org/10.1594/PANGAEA.918023, https://doi.org/10.1594/PANGAEA.918033, https://doi.org/10.1594/PANGAEA.918028, https://doi.org/10.1594/PANGAEA.918024, https://doi.org/10.1594/PANGAEA.918034, https://doi.org/10.1594/PANGAEA.918029, https://doi.org/10.1594/PANGAEA.918025, https://doi.org/10.1594/PANGAEA.918035, https://doi.org/10.1594/PANGAEA.918030, https://doi.org/10.1594/PANGAEA.918026, https://doi.org/10.1594/PANGAEA.918036, and https://doi.org/10.1594/PANGAEA.918031.