bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nirmatrelvir treatment of SARS‐CoV‐2‐infected mice blunts antiviral adaptive immune responses
Authors: Fumagalli Valeria , Di Lucia Pietro , Ravà Micol , Marotta Davide , Bono Elisa , Grassi Stefano , Donnici Lorena , Cannalire Rolando , Stefanelli Irina , Ferraro Anastasia , Esposito Francesca , Pariani Elena , Inverso Donato , Montesano Camilla , Delbue Serena , Perlman Stanley , Tramontano Enzo , De Francesco Raffaele , Summa Vincenzo , Guidotti Luca G , Iannacone Matteo 
Published: March 2023

AbstractAlongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS‐CoV‐2 pandemic. Nirmatrelvir—an orally available inhibitor of the 3‐chymotrypsin‐like cysteine protease—has been shown to reduce the risk of progression to severe COVID‐19. However, the impact of nirmatrelvir treatment on the development of SARS‐CoV‐2‐specific adaptive immune responses is unknown. Here, by using mouse models of SARS‐CoV‐2 infection, we show that nirmatrelvir administration blunts the development of SARS‐CoV‐2‐specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir‐treated mice recruited significantly fewer memory T and B cells to the infected lungs and mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals.
Structural and dynamic properties of the YTH domain in complex with N6‐methyladenosine RNA studied by accelerated molecular dynamics simulations
Authors: Li Mingwei , Chen Guanglin , Zhang Zhiyong 
Published: March 2023

BackgroundN6‐methyl adenosine (m6A) modifications of mRNA and long non‐coding RNA (lncRNAs) are known to play a significant role in regulation of gene expression and organismal development. Besides writer and eraser proteins of this dynamic modification, the YT521‐B homology (YTH) domain can recognize the modification involved in numerous cellular processes. The function of proteins containing YTH domain and its binding mode with N6‐Methyladenosine RNA has attracted considerable attention. However, the structural and dynamic characteristics of the YTH domain in complex with m6A RNA is still unknown.MethodThis work presents results of accelerated molecular dynamics (aMD) simulations at the timescale of microseconds. Principal component analysis (PCA), molecular mechanics generalized Born surface area (MM/GBSA) calculations, contact analysis and contact‐based principal component analysis (conPCA) provide new insights into structure and dynamics of the YTH‐RNA complex.ResultsThe aMD simulations indicate that the recognition loop has a larger movement away from the binding pocket in the YTH‐A3 RNA than that in the YTH‐m6A3 RNA. In aMD trajectories of the apo YTH, there is a significant close‐open transition of the recognition loop, that is to say, the apo YTH can take both the closed and open structure. We have found that the YTH domain binds more favorably to the methylated RNA than the non‐methylated RNA. The per‐residue free energy decomposition and conPCA suggest that hydrophobic residues including W380, L383‐V385, W431‐P434, M437, and M441‐L442, may play important roles in favorable binding of the m6A RNA to the YTH domain, which is also supported by aMD simulations of a double mutated system (L383A/M437A).ConclusionThe results are in good agreement with higher structural stability of the YTH‐m6A RNA than that of the YTH‐A3 RNA. The addition of a methylation group on A3 can enhance its binding to the hydrophobic pocket in the YTH domain. Our simulations support a ‘conformational selection’ mechanism between the YTH‐RNA binding. This work may aid in our understanding of the structural and dynamic characteristics of the YTH protein in complex with the methylated RNA.
Quantitative functionalization of biosynthetic caged protein materials
Authors: Cheng Quan , Wang Xuan , Zhang Xian‐En , Xu Chengchen , Li Feng 
Published: March 2023

BackgroundAs one of the representative protein materials, protein nanocages (PNCs) are self‐assembled supramolecular structures with multiple advantages, such as good monodispersity, biocompatibility, structural addressability, and facile production. Precise quantitative functionalization is essential to the construction of PNCs with designed purposes.ResultsWith three modifiable interfaces, the interior surface, outer surface, and interfaces between building blocks, PNCs can serve as an ideal platform for precise multi‐functionalization studies and applications. This review summarizes the currently available methods for precise quantitative functionalization of PNCs and highlights the significance of precise quantitative control in fabricating PNC‐based materials or devices. These methods can be categorized into three groups, genetic, chemical, and combined modification.ConclusionThis review would be constructive for those who work with biosynthetic PNCs in diverse fields.
Modeling the relationship between gene expression and mutational signature
Authors: Jiang Limin , Yu Hui , Guo Yan 
Published: March 2023

BackgroundMutational signatures computed from somatic mutations, allow an in‐depth understanding of tumorigenesis and may illuminate early prevention strategies. Many studies have shown the regulation effects between somatic mutation and gene expression dysregulation.MethodsWe hypothesized that there are potential associations between mutational signature and gene expression. We capitalized upon RNA‐seq data to model 49 established mutational signatures in 33 cancer types. Both accuracy and area under the curve were used as performance measures in five‐fold cross‐validation.ResultsA total of 475 models using unconstrained genes, and 112 models using protein‐coding genes were selected for future inference purposes. An independent gene expression dataset on lung cancer smoking status was used for validation which achieved over 80% for both accuracy and area under the curve.ConclusionThese results demonstrate that the associations between gene expression and somatic mutations can translate into the associations between gene expression and mutational signatures.
Expanding digitalisation for subsistence and sustainability in the heart of Europe, based on the examples of Hungarian companies
Authors: Katona Andrea , Birkner Zoltán , Péter Erzsébet 
Published: March 2023

AbstractThe rapid technological development that is still taking place today, with increasingly interconnected IT tools, is introducing dramatic changes. The development of computer programs is rapidly transforming traditional processes and the systems that support them. It is therefore natural that the fourth industrial revolution (Industry 4.0) and its impact on Hungarian companies is one of the key topics of our time. We conducted an exploratory quantitative survey, asking 140 managers of Hungarian small, medium and large enterprises about their current situation in the context of Industry 4.0. We sought to find out to what extent the specific R&D and innovation potential of Industry 4.0 is accepted, and whether it has already been introduced in the companies. On a qualitative side, 2 case studies and 3 interviews were conducted, in which structured interviews were used to further explore the issue. We aimed to find out where SMEs stood in terms of digital preparedness and what advantages, possible disadvantages, and goals they managed to identify. Our research showed that an increasing number of companies have already decided to take the first steps towards industrial digitalisation, which will completely transform their internal processes.
DEMOCRACIA, PROCESSO ELEITORAL E FAKE NEWS: UM PLANO DE AULA PARA O ENSINO FUNDAMENTAL
Authors: Souza Fátima , Brandão Cleyton , Brito Rocha Telma 
Published: March 2023

Esse artigo apresenta um plano de aula do componente curricular Língua Portuguesa, do 6º ao 9º ano do Ensino Fundamental II, sobre Democracia, Fake News e Processo Eleitoral Brasileiro. A abordagem metodológica é qualitativa, na qual utilizou-se a revisão de literatura, sobre democracia e educação, contribuições da temática na Base Nacional Comum Curricular (BNCC), que destaca ser necessário desenvolver nos educandos habilidades para analisar o fenômeno da disseminação de notícias falsas nas redes sociais, e o conhecimento de gêneros textuais da esfera pública e das leis em um estado democrático, bem como, uma reflexão ação sobre a prática pedagógica a partir de um plano de aula. Como resultado, uma proposta para ensino híbrido, sobre práticas de linguagem, leitura, produção de efeitos de sentido de textos que circulam no campo de atuação na vida pública, o entendimento do processo eleitoral brasileiro e como as fake news afetam a democracia
Infections and causative microorganisms in patients with ANCA-associated vasculitis
Authors: VARKAL Gizem , TÜRK İpek , DOĞAN AĞBUGA Özlem , AŞIK Mehmet Ali , ZENGİN ACEMOĞLU Şerife Şeyda , AYDIN Kaniye , ARSLAN Didem , ÖZER Hüseyin Turgut Elbek 
Published: March 2023

Purpose: The aim of this study was to detect infections requiring hospitalization in patients with ANCA-associated vasculitis (AAV).
Materials and Methods: This is a single-center, retrospective study conducted in Turkish patients with AAV. Infection episodes requiring hospitalization, reproducing pathogens, laboratory findings, immunosuppressive treatments given for the treatment of vasculitis, and the relationship with the infection were evaluated.
Results: Seventy-four patients diagnosed with AAV were included in the study. Hospitalization due to infection was observed in 36 of the patients. The coexistence of diabetes mellitus (DM) was found to be significantly higher in the infected patient group. Cyclophosphamide (CYC) treatment found to increase risk of infection. More than 80% of the infected patient group presented with renal involvement (80.6%). A total of 68 infectious episodes were seen in 36 patients. The most common involvement of infection was the respiratory tract with a rate of 70.6%. Gram-negative bacteria were the most common pathogen, especially Pseudomonas aeruginosa. With the effect of the pandemic, SARS-CoV-2 has come to the fore among viral infections. Aspergillosis was the most frequently detected among fungal infections. Besides, aspergillosis was the cause of 85.7% (6 episodes) of fungal infections. Lymphopenia was observed in 76.5% of the infection episodes. 57.4% of infections developed in the first year of the induction therapy. The most frequently used immunosuppressive therapy for the treatment of vasculitis in infectious episodes was CYC (41.2%).
Conclusion: Managing infections during the vasculitis treatment is crucially important. Lymphopenia, kidney involvement, DM and immunosuppressive therapy are factors that increase the risk of infection. Clinicians should take preventive measure especially for respiratory tract infections and gram-negative bacteria as pathogens.
Investigation of the relationship between NFKB1 polymorphisms and telomere length and apoptosis in patients with type-2 diabetes
Authors: DİRİCAN Ebubekir , KAYA Yasemin 
Published: March 2023

Purpose: Type 2 diabetes mellitus (T2DM) is a heterogeneous, chronic, and metabolic disease that affects a significant proportion of the global population. This study aimed to evaluate the effect of NFKB1 -94 ATTG ins/del polymorphisms on the expression of apoptosis genes and telomere length (TL) in patients with T2DM compared with healthy individuals.
Materials and Methods: Sixty-nine T2DM patients and sixty healthy people were enrolled in the study. DNA and RNA were isolated from the blood samples. NFKB1 genotypes were identified by Sanger sequencing. For TL analyses and to investigate the expression of the caspase-3, caspase-9, bax, and bcl2 genes, RT-PCR was utilized.
Results: There was a significant difference between the NFKB1 -94 ins/del genotype patients and the control group (OR:0.4792 (0.2345-1.011)). However, the distribution of other genotype/alleles (ins/ins and del/del) showed no difference between T2DM and control groups. The allelic frequency of NFKB1 -94 ins/del was 0.455/0.235 for the T2DM group and 0.435/0.165 for the control group. An increase in the mRNA expression of caspase-3, caspase-9 and Bax genes was observed in the T2DM group compared with the healthy group, while a decrease in the Bcl2 gene was found in the T2DM group. TL in T2DM patients was shorter than in healthy individuals.
Conclusion: NFKB1 -94 ins/del polymorphisms show significant differences in T2DM patients. We observed that apoptosis was activated and TL was shortened in patients with T2DM. However, no relationship between NFKB1 polymorphisms and apoptosis and TL could not be determined.
Regional seismic discriminants using wave-train energy ratios
Authors: Woods Bradley B. , Helmberger Donald V. 
Published: March 2023

AbstractWe have examined broadband regional waveforms of recent (since 1988) Nevada Test Site (NTS) underground explosions and earthquakes throughout the southwestern United States and Baja, Mexico, recorded by TERRAscope and other IRIS stations in order to characterize seismic sources for the purposes of event identification. As expected, earthquakes tended to be richer in long-period surface-wave and short-period shear-wave energy relative to explosions of comparable P-wave strength. Also, explosions, in general, were found to be richer in 1- to 6-sec surface-wave (Rg) energy and other late-arriving coda energy than were earthquakes. Most earthquakes show relatively little long-period (T &gt; 6 sec) Rg and surface-wave coda energy, which we attribute to their deeper source depths, whereas known shallow earthquakes do exhibit these phases. We have developed several seismic discriminants based on our observations. The most promising discriminant is the ratio of short-period (f ≧ 1.0 Hz), vertical component, Pnl wave-train energy (EspPz) to long-period (0.05 to 0.167 Hz), three-component, surface-wave energy (Elp−3). For this ratio, explosions tend to have a higher value than do earthquakes. This discriminant works on the same premise as the teleseismic mb:MS ratio, for which earthquakes are richer in long-period surface-wave energy relative to explosions with the same body-wave magnitude. The long-period passband was chosen to limit the effect of longer-period noise and to remove the effect of the coda surface waves. Another potential discriminant examined is the ratio of short-period (f ≧ 1.0 Hz), vertical-component, P-wave to S-wave energy (EspPz:EspSz). We find that this criterion only yields marginal separation of the source populations but becomes more effective at higher frequency bands (f ≧ 4.0 Hz) or when looking at single-station observations. It does, however, help to quantify significant short-period waveform differences between the three test subsites, with Pahute Mesa shots generating relatively little S-wave energy compared to those of Yucca Flat for which the S wave (or Lg) is often the largest phase, while Rainier's shots are intermediate in character with distinct but less prominent S waves. This S-wave generation is thought to be caused by near-source scattering to converted phases and appears to be highly dependent on the near-source geology. These two discriminants are useful in that they are simple and fast to calculate. Using regional stations for sources 200 to 1300 km away, the magnitude threshold for the EspPz:Elp−3 discriminant is roughly ML ≧ 4.0, the limiting factor being the signal level of the Airy phase, while that for the EspPz:EspSz discriminant is roughly ML ≧ 3.0 for the same distance ranges.
Faktor-Faktor yang Mempengaruhi Pasien Umum Memilih Instalasi Rawat Inap Rumah Sakit Wava Husada Selama Masa Pandemi Covid-19
Authors: Salsabila Miranda Gracia , Adi Sapto , Fanani Erianto , Hapsari Anindya 
Published: March 2023

Abstract: Researchers wanted to know what factors influence the general public in choosing to stay at Wava Husada Hospital during the Covid-19 pandemic because many people were afraid to go to hospital, especially if they have to be hospitalized. The reason for choosing Wava Husada Hospital was because this hospital was a type B hospital with the highest number of visits located in Malang Regency. This study used a qualitative method with In-depth Interview technique to collect data from informants. The population of this study were non BPJS patients who were hospitalized at Wava Husada Hospital, while the number of informants selected in this study were three people. The data were analyzed by transcribing the entire interview process with the informants and then grouped by concept which would then be analyzed to find conclusions. It can be found six factors that influence the community to do hospitalization at Wava Husada Hospital, the six factors were the location of the hospital, the cleanliness of the hospital, the proximity of the patient to medical personnel (doctors and nurses), the services provided by the hospital, the facilities owned by the hospital. by the hospital, and the last was the experience of others. The factor that most influences informants in making decisions was the closeness between patients and doctors and nurses.
Abstrak: Peneliti ingin mengetahui faktor apa saja yang mempengaruhi masyarakat umum dalam memilih melakukan rawat inap di Rumah Sakit Wava Husada selama masa pandemi Covid-19 karena banyak masyarakat yang takut untuk berobat ke rumah sakit, apalagi jika harus melakukan rawat inap. Alasan dari dipilihnya Rumah Sakit Wava Husada yaitu karena rumah sakit ini merupakat rumah sakit tipe B dengan jumlah kunjungan terbanyak yang terletak di Kabupaten Malang. Penelitian ini menggunakan metode kualitatif dengan teknik In-depth Interview untuk mengumpulkan data dari informan. Populasi penelitian ini yaitu pasien non BPJS yang melakukan rawat inap di Rumah Sakit Wava Husada, sedangkan jumlah informan yang terpilih dalam penelitian ini yaitu sebanyak tiga orang. Data dianalisis dengan cara menstraskripkan seluruh proses wawancara dengan informan lalu dikelompokkan berdasarkan konsep yang kemudian akan dianalisa untuk mencari kesimpulan. Dapat ditemukan enam faktor yang mempengaruhi masyarakat untuk melakukan rawat inap di Rumah Sakit Wava Husada, keenam faktor tersebut yaitu lokasi rumah sakit, kebersihan rumah sakit, kedekatan pasien dengan tenaga medis (dokter dan perawat), pelayanan yang diberikan oleh rumah sakit, fasilitas yang dimiliki oleh rumah sakit, dan yang terakhir yaitu pengalaman orang lain. Faktor yang paling mempengaruhi informan dalam mengambil keputusan yaitu kedekatan antara pasien dengan dokter dan juga perawat.
Interpretation Threshold Values for the Oxford Hip Score in Patients Undergoing Total Hip Arthroplasty
Authors: Harris Lasse K. , Troelsen Anders , Terluin Berend , Gromov Kirill , Overgaard Søren , Price Andrew , Ingelsrud Lina H. 
Published: March 2023

Background:
Patient-reported outcome measures such as the Oxford Hip Score (OHS) can capture patient-centered perspectives on outcomes after total hip arthroplasty (THA). The OHS assesses hip pain and functional limitations, but defining interpretation threshold values for the OHS is warranted so that numerical OHS values can be translated into whether patients have experienced clinically meaningful changes. Therefore, we determined the minimal important change (MIC), patient acceptable symptom state (PASS), and treatment failure (TF) threshold values for the OHS at 12 and 24-month follow-up in patients undergoing THA.

Methods:
This cohort study used data from patients undergoing THA at 1 public hospital between July 2016 and April 2021. At 12 and 24 months postoperatively, patients provided responses for the OHS and for 3 anchor questions about whether they had experienced changes in hip pain and function, whether they considered their symptom state to be satisfactory, and if it was not satisfactory, whether they considered the treatment to have failed. The anchor-based adjusted predictive modeling method was used to determine interpretation threshold values. Baseline dependency was evaluated using a new item-split method. Nonparametric bootstrapping was used to determine 95% confidence intervals (CIs).

Results:
Complete data were obtained for 706 (69%) of 1,027 and 728 (66%) of 1,101 patients at 12 and 24 months postoperatively, respectively. These patients had a median age of 70 years, and 55% to 56% were female. Adjusted OHS MIC values were 6.3 (CI, 4.6 to 8.1) and 5.2 (CI, 3.6 to 6.7), adjusted OHS PASS values were 30.6 (CI, 29.0 to 32.2) and 30.5 (CI, 29.3 to 31.8), and adjusted OHS TF values were 25.5 (CI, 22.9 to 27.7) and 27.0 (CI, 25.2 to 28.8) at 12 and 24 months postoperatively, respectively. MIC values were 5.4 (CI, 2.1 to 9.1) and 5.0 (CI, 1.9 to 8.7) higher at 12 and 24 months, respectively, in patients with a more severe preoperative state.

Conclusions:
The established interpretation threshold values advance the interpretation and clinical use of the OHS, and may prove especially beneficial for registry-based evaluations of treatment quality.

Level of Evidence:
Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Belle Infidèle
Authors: García Martínez Aurora María 
Published: March 2023

Constant d’Hermenches, Benjamin Constant, Charles-Emmanuel de Charrière, Camille et Pierre Malarmey ont tous un point en commun, une femme: Isabelle de Charrière. Ces hommes, entre autres, parsemèrent le chemin de Belle et jouèrent un rôle important dans sa vie monotone. Par les documents reccueillis dans cet article, il nous sera possible de savoir si ce rôle se limita à une innocente amitié ou alors, traversa les frontières de la décence faisant de Belle une infidèle.
Constant d’Hermenches, Benjamin Constant, Charles-Emmanuel de Charrière, Camille y Pierre Malarmey tienen todos un punto en común, una mujer: Isabelle de Charrière. Estos hombres, entre otros, se cruzaron en el camino de Belle y jugaron un papel importante en su monótona vida. Los documentos recopilados en este artículo nos permitirán averiguar si dicho papel solo fue una inocente amistad o traspasó las fronteras del decoro haciendo de Belle una infiel.
EL AMOR BRUJO A TRAVÉS DE LA CRÍTICA MUSICAL
Authors: Barbero Consuegra Gabriel , Barbero Consuegra David 
Published: March 2023

El Amor Brujo es propuesto a Falla por Gregorio Martínez Sierra. Se tenía la idea de un texto cantado, con la inclusión de algunos fragmentos de danza. Para gran parte de los críticos de la época, El Amor Brujo era una obra de difícil calificación.
MÚSICA Y PERSPECTIVA HISTÓRICA.
Authors: Prados Sillero Oscar 
Published: March 2023

Hoy en día, la música del pasado se pone relación con su propio sistema de referencia estético y, en función de ese contraste, se la valora. Las cualidades estéticas de la música procedentes de las características de ésta en lo relativo al tiempo y las circunstancias de composición eran muy diferentes a comienzos del siglo XIX de como lo son actualmente. Perspectiva histórica es por tanto un concepto fundamental.