bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGARUH KESADARAN BERPOLITIK TERHADAP PARTISIPASI POLITIK KAUM MILLENIAL
Authors: Sutjipto Vera Wijayanti , Putri Maulina Larasati , Sary Marisa Puspita , Putri Angieta Dewati , Wulandari Helyana , Fauziyah Hasna Nur
Published: July 2023

Political awareness has an important role as one of the basic needs in forming one's political views. The influence and political direction of the millennial generation in democratic life can be shown from three factors, including: (1) potential for political participation and choice beliefs, (2) sensitivity to social issues and policies, and (3) inclination towards candidates and political choices. This study uses a descriptive quantitative method which has the aim of explaining and summarizing various conditions regarding political awareness among millennials. The population of this study is millennials aged 18 to 22 years who live in Greater Jakarta. The research data was collected by questionnaire from 100 respondents. The results of this study indicate that there is a significant influence between political awareness on political participation. The interest in political developments in Indonesia indicates that slowly the millennial generation is starting to realize the magnitude of the changes that politics will bring.
PENGARUH GAYA KEPEMIMPINAN, BUDAYA ORGANISASI, KOMITMEN ORGANISASI TERHADAP KINERJA KARYAWAN (STUDI PADA KARYAWAN PT. VICTORY RETALINDO CABANG CIKARANG)
Authors: Julianingsih Desi , Nisawati Inna
Published: July 2023

This study aims to determine whether there is a significant influence ofLeadership Style, Organizational Culture, and Organizational Commitment on Employee Performance at PT. Victory Retalindo Cikarang branch. With the population and sample in this study as many as 70 respondents. What needs to be known is that human resources are an important factor that is always in the company because to achieve a company's vision by carrying out the mission is basically governed by humans. Including companies in the retail sector, namely PT. Victory Retalindo Cikarang branch. Leadership style is a pattern of behavior of a typical leader when influencing his subordinates, what the leader chooses to do. Organizational culture is a system of values, norms and beliefs shared by a group of people in an organization that differentiates it from the others. Organizational commitment is where employees are very interested in the goals, values, and goals of the organization. Employee Performance is the ability, skills, and work results shown by an employee in carrying out their duties and responsibilities at work.The results of the R2 test which was carried out to test how much influence the independent variables had on the dependent variable in this study showed a figure of 87.7% while the other 12.3% were influenced by other factors. Leadership Style (X1) partially affects Employee Performance (Y) with a significance value of 0.007 or less than 0.05 and is declaredacceptable. Organizational Culture Variable (X2) partially affects Employee Performance (Y) with a significance value of 0.000 or less than 0.05 and is declared accepted. Organizational Commitment (X3) partially affects Employee Performance (Y) with a significance value of 0.000 or less than 0.05 and is declared accepted. Simultaneously the variables Leadership Style (X1), Organizational Culture (X2), Organizational Commitment (X3) have a positive effect on Employee Performance (Y) with a significance value of 0.00 or less than 0.05.
ANALISIS KNOWLEDGE SHARING TERHADAP KINERJA UKM BERBASIS SIKAP KEWIRAUSAHAAN DI KOTA BANJARMASIN
Authors: Huda Isra Ul , Karsudjono Anthonius Junianto
Published: July 2023

This study aims to determine and also analyze the effect of knowledge sharing onentrepreneurial attitudes and also the performance of SMEs in the city of Banjarmasin. This study uses quantitative data analysis methods, the sample in this study is SMEs in the city of Banjarmasin which are divided into 10 people in each sub-district with a total of 50 respondents. PLS analysis tool. The results of the analysis carried out prove that knowledge sharing has a direct, positive and significant effect on entrepreneurial attitudes and also the performance of SMEs in the city of Banjarmasin. Then the entrepreneurial attitude has a direct, positive and significant influence on the performance of SMEs in the city of Banjarmasin. This study also proves that there is an indirect, positive and significant effect between the performance of SMEs in the city of Banjarmasin through entrepreneurial attitudes.
OPTIMASI CAMPURAN AVICEL 101 DAN LAKTOSA SEBAGAI BAHAN PENGISI PADA TABLET DISPERSI PADAT TADALAFIL DENGAN METODE GRANULASI BASAH
Authors: Manno Mohamad Reski , Setianto Arif Budi
Published: July 2023

INTISARI Pengembangan formula obat dalam industri farmasi sangatlah penting, dimana komposisi formula yang optimum dapat mempengaruhi sediaan farmasetis yang memenuhi persyaratan sesuai CPOB. Tadalafil merupakan obat yang berkhasiat sebagai terapi disfungsi ereksi yang diformulasikan dalam sediaan padat berupa tablet dengan metode granulasi. Penelitian ini bertujuan untuk mendapatkan formula optimum tablet dispersi padat tadalafil dengan campuran avicel 101 dan laktosa sebagai bahan pengisi dengan metode granulasi basah. Granul dispersi padat tadalafil dibuat dengan perbandingan kosentrasi bahan pengisi avicel 101 dan laktosa yaitu 5:5, 4:6, dan avicel 101 tanpa kombinasi laktosa. Evaluasi sediaan meliputi uji waktu alir granul, uji sudut diam, uji pengetapan, kadar air granul, uji kekerasan, uji keseragaman bobot, uji keseragaman ukuran, kerapuhan dan waktu hancur tablet. Hasil penelitian menunjukan bahwa formula dengan kombinasi avicel 101 dan laktosa sebagai bahan pengisi dapat menghasilkan formula granul dan tablet dengan karakteristik yang baik.Kata kunci: (Avicel 101, Granul, Laktosa, Tablet, Tadalafil)
The Rural Hinterland of Antipatris from the Hellenistic to the Byzantine Periods
Authors: Amit Shadman
Published: July 2023

The Rural Hinterland of Antipatris from the Hellenistic to the Byzantine Periods presents the results of extensive excavations conducted in the rural region south and east of the modern city of Rosh Ha’Ayin. The archaeological and historical data that are analysed span a period of over 1000 years.

To examine the settlement pattern of the region, 22 sites were chosen, divided into five primary models, which represent a hierarchal settlement pattern: farmsteads; subsidiary villages; fortresses; monasteries and churches; towns. These five settlement types were examined throughout the periods under study. Emphasis is consistently placed on landscape archaeology – rural roads, field towers, plot boundaries, oil presses, winepresses, and terraces. A key aim is to date the creation of agricultural systems and to track the potential areas of cultivation of different agricultural products.

Twelve sites dating to the Hellenistic period were found, most being farmsteads established in the Iron Age II and functioning until the 3rd Century BCE, when they were abandoned in an organized manner, possibly in the transition between Ptolemaic and Seleucid rule. During the Roman Period a dramatic decline in settlement distribution is noted, with a total of only five sites known - and among them only one large village – Migdal-Afek. Twenty more settlements from the Byzantine period were discovered, indicating a significant rise in their number from the Roman period. The settlements include large villages, manor houses and monasteries which functioned from the 5th to 8th centuries.
Caracterização de agravos à saúde do idoso em um serviço móvel de urgência: revisão de literatura
Authors: Santos Maria Carolina Salustino dos , Silva Maria Beatriz de Andrade , Ramalho Juliana Paiva Góes , Melo Maria Raquel Thomaz Tertuliano de , Olanda Débora Evelly da Silva , Miranda Allana Petrúcia Medeiros de , Costa Marcele Ferreira da , Sousa Edilma Magda de , Marques Maria Lúcia Fernandes de Carvalho , Santos Wallison Pereira dos , Silva Juçara Elke Lourenço da , Saldes Alessandra Aparecida de , Macêdo Ingryd Karollyne Vilar Ferreira , Gomes Damiana Cristina Rodrigues , Coelho Gleciane de Paulo , Ferreira Jéssica Leny Gomes
Published: July 2023

A visível elevação da população idosa faz necessário o desenvolvimento da assistência qualificada de urgência e emergência a esses indivíduos, visto que, a grande maioria possui comorbidades relacionadas às doenças crônicas degenerativas. O Serviço de Atendimento Móvel de Urgência (SAMU) objetiva assegurar um atendimento precoce, rápido e adequado. Nesse sentido, esse estudo teve como objetivo: Analisar as evidências científicas acerca dos agravos comuns que mais acometem a pessoa idosa atendida pelo SAMU. Para conseguir realizar a análise e discussões acerca da temática, foi desenvolvida uma pesquisa do tipo ensaio teórico, obedecendo às etapas: formulação do problema da pesquisa; estabelecimento dos critérios para inclusão ou exclusão dos estudos encontrados nas bases disponíveis; definição das informações a serem extraídas dos artigos selecionados; avaliação dos dados; interpretação dos resultados e apresentação final. A pesquisa foi efetuada por meio de um levantamento de dados e busca bibliográfica nas bibliotecas e bases de dados: BVS, BDENF, LILACS e SCIELO. A seleção das produções científicas considerou estudos publicados entre 2010-2020; nos idiomas português, inglês e espanhol; ser realizado com pessoas de 60 anos ou mais; devendo se tratar do atendimento de urgência e emergência e pré-hospitalar móvel. Foi apontado que todos os estudos são brasileiros, sendo a maioria no campo da enfermagem, os agravos mais evidentes foram os traumáticos e relacionados às condições clínicas, principalmente do sexo feminino e entre as idades de 60 e 79 anos. As análises das leituras demonstraram a preocupação dos autores quanto ao conhecimento dos profissionais do setor de urgência e emergência acerca da geriatria e gerontologia, fator que interfere diretamente na assistência prestada, motivo que ressalta a importância de uma reeducação dos profissionais de saúde acerca de uma assistência segura.
Kearifan Lokal dalam Cerita Rakyat Kabupaten Bangka sebagai Bentuk Nilai Budaya dan Pendidikan Karakter
Authors: Rahmaniyar Atik
Published: July 2023

Abstrak
Cerita rakyat merupakan sebuah cerita yang memiliki ciri khas dari setiap daerah masing-masing. Refleksi kehidupan sehari-hari masyarakat tiap daerah biasanya tersisipkan pada cerita rakyat yang disampaikan. Artikel ini berisi tentang kearifan lokal dalam cerita rakyat Kabupaten Bangka sebagai bentuk nilai budaya dan pendidikan karakter. Upaya pelestarian sastra lama dengan menggali nilai budaya dan pendidikan karakter yang selaras dengan kearifan lokal daerah merupakan tujuan utama dalam menyampaikan kepada para pembaca maupun para anak didik di tengah era modern yang makin menggerus cerita-cerita lama. Penelitian ini bertujuan untuk menjelaskan nilai-nilai kearifan lokal (nilai budaya dan pendidikan karakter) yang terkandung dalam cerita rakyat Kabupaten Bangka. Teori yang digunakan dalam penelitian ini adalah cerita rakyat dan nilai kearifan lokal berupa nilai budaya dan pendidikan karakter. Analisis nilai budaya dan pendidikan karakter menggunakan teori yang disampaikan Robert Sibarani serta menggunakan metode deskriptif analitis.
Kata kunci: cerita rakyat, kearifan lokal, nilai budaya, pendidikan karakter.
Kajian Motif dan Makna Kain Tenun Cual Masyarakat Bangka
Authors: Harikiswanto Harikiswanto
Published: July 2023

Penelitian ini pada hakikatnya menyangkut tentang pengkajian motif kain tenun Cual yang terletak di Koperasi Ibu Maslina Yazid dengan berbagai informan kunci yaitu keluarga besar Bapak Yazid beserta beberapa perajin tenun yang sudah ahli. Tujuan dilakukannya penelitian ini yaitu untuk menemukan, menggali serta mengeksplorasikan beberapa hal yang terkandung dalam setiap motif kain tenun Cual. Metode yang digunakan dalam penelitian ini yaitu metode deskriptif kualitatif dengan menggunakan pendekatan budaya. Sedangkan teknik yang digunakan dalam mengumpulkan data yaitu dengan cara observasi dan wawancara. Adapun temuan-temuan yang diperoleh dari penelitian ini adalah berupa sejarah perkembangan kain tenun Cual, jenis-jenis motif, bahasa rupa yang terkandung dalam motif, inovasi motif dan bentuk kain, teknik-teknik yang digunakan, serta serangkaian proses yang harus dilakukan dalam menciptakan kain tenun Cual Bangka
Condensation of α,ω-Oligodimethylsiloxanols in Ammonia: A New Method for the Synthesis of Polydimethylsiloxanes with the Low Content of Cyclosiloxanes
Authors:   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, str. 1, Moscow, 119334 Russia, Minyaylo E. O. ,   Tula State Lev Tolstoy Pedagogical University, pr. Lenina 125, korp. 4, Tula, 300026 Russia, Ershova T. O. ,   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, str. 1, Moscow, 119334 Russia,   Tula State Lev Tolstoy Pedagogical University, pr. Lenina 125, korp. 4, Tula, 300026 Russia, Temnikov M. N. ,   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, str. 1, Moscow, 119334 Russia,   Tula State Lev Tolstoy Pedagogical University, pr. Lenina 125, korp. 4, Tula, 300026 Russia, Anisimov A. A. ,   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, str. 1, Moscow, 119334 Russia,   Tula State Lev Tolstoy Pedagogical University, pr. Lenina 125, korp. 4, Tula, 300026 Russia,   Moscow Institute of Physics and Technology (National Research University), Institutskiy per. 9, Dolgoprudny, Moscow Oblast, 141700 Russia
Published: July 2023

A new efficient approach to the production of high molecular weight polydimethylsiloxanes (PDMSs) is developed based on the condensation of α,ω-oligodimethylsiloxanols in ammonia. This method provides control over the molar mass of the target PDMSs in a wide range (Mw = 11.0–82.0 kg/mol). The use of cyclic silazanes as dehydrating agents allows for suppressing the side cyclization processes.
Synthesis of (E)-2-Cyano-5-phenylpent-2-en-4-ynoic Acid Esters and N-Substituted Amides
Authors:   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, str. 1, Moscow, 119334 Russia, Golding I. R. , Klemenkova Z. S. ,   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, str. 1, Moscow, 119334 Russia, Kharitonova V. G. ,   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, str. 1, Moscow, 119334 Russia, Kupriyanova D. V. ,   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, str. 1, Moscow, 119334 Russia, Kovalev A. I. ,   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, str. 1, Moscow, 119334 Russia, Khotina I. A. ,   Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, str. 1, Moscow, 119334 Russia
Published: July 2023

(E)-2-Сyano-5-phenylpent-2-en-4-ynoic acid esters and N-substituted amides were synthesized by the Knoevenagel condensation of 3-phenylpropiolaldehyde with the corresponding cyanoacetates or cyanoacetamides in the presence of basic alumina used as a catalyst. The IR and Raman spectra of the resulting compounds show strong absorption bands in the range of 1565–1580 cm–1 which are attributed to the vibrations of the C=C bond in the enyl moiety.
Pediatric and Adolescent Gynecology: Practical Guide
Authors: Ivanov D.O. , Rukhlyada N.N.
Published: July 2023

Gynecology
The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF): feasibility trial protocol
Authors: Lewis Amanda , Clout Madeleine , Benger Jonathan , Braude Philip , Turner Nicholas , Gagg James , Gendall Emma , Holloway Simon , Ingram Jenny , Kandiyali Rebecca , Maskell Nick , Shipway David , Smith Jason E , Taylor Jodi , Darweish-Medniuk Alia , Carlton Edward
Published: July 2023

Background: Topical lidocaine patches, applied over rib fractures, have been suggested as a non-invasive method of local anaesthetic delivery to improve respiratory function, reduce opioid consumption and consequently reduce pulmonary complications. Older patients may gain most benefit from improved analgesic regimens yet lidocaine patches are untested as an early intervention in the Emergency Department (ED). The aim of this trial is to investigate uncertainties around trial design and conduct, to establish whether a definitive randomised trial of topical lidocaine patches in older patients with rib fractures is feasible. Methods: RELIEF is an open label, multicentre, parallel group, individually randomised, feasibility randomised controlled trial with economic scoping and nested qualitative study. Patients aged ≥ 65 years presenting to the ED with traumatic rib fracture(s) requiring admission will be randomised 1:1 to lidocaine patches (intervention), in addition to standard clinical management, or standard clinical management alone. Lidocaine patches will be applied immediately after diagnosis in ED and continued daily for 72 hours or until discharge. Feasibility outcomes will focus on recruitment, adherence and follow-up data with a total sample size of 100. Clinical outcomes, such as 30-day pulmonary complications, and resource use will be collected to understand feasibility of data collection. Qualitative interviews will explore details of the trial design, trial acceptability and recruitment processes. An evaluation of the feasibility of measuring health economics outcomes data will be completed. Discussion: Interventions to improve outcomes in elderly patients with rib fractures are urgently required. This feasibility trial will test a novel early intervention which has the potential of fulfilling this unmet need. The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF) feasibility trial will determine whether a definitive trial is feasible. ISRCTN Registration: ISRCTN14813929 (22/04/2021).
Overconsolidated Stress and Strain Condition of Pavement Layers as a Result of Preloading during Construction
Authors: Vámos Máté János , Szendefy János
Published: July 2023

The stiffness and resilient behavior of soils are essential input properties when designing pavements. There are many material models that take into account the stress dependency of stiffness. In pavements, horizontal stresses generally differ from conventional soils because of the preloading of the pavement during construction. In this research, standardized pavement cross sections were analyzed using finite element software with advanced soil constitutive models, and equations describing their behavior were calibrated with the back-analysis of in-situ and laboratory measurements. The pavement was modelled as comprising 4 layers: asphalt pavement, well graded crushed stone base course, granular subbase course and fine-medium sandy subgrade. The ratio of horizontal and vertical stresses σ3/σ1 and strains ε3/ε1 were investigated and assessed in the function of depth and loading, and recommendations are given for the description of these functions. The recommendations give useful input data for future practical applications such as simplified calculation methods that are capable of determining the permanent settlement beneath flexible pavements without the use of finite element methods.
Preclinical in vitro evaluation of implantable materials: conventional approaches, new models and future directions
Authors: Frisch Emilie , Clavier Lisa , Belhamdi Abdessamad , Vrana Nihal Engin , Lavalle Philippe , Frisch Benoît , Heurtault Béatrice , Gribova Varvara
Published: July 2023

Nowadays, implants and prostheses are widely used to repair damaged tissues or to treat different diseases, but their use is associated with the risk of infection, inflammation and finally rejection. To address these issues, new antimicrobial and anti-inflammatory materials are being developed. Aforementioned materials require their thorough preclinical testing before clinical applications can be envisaged. Although many researchers are currently working on new in vitro tissues for drug screening and tissue replacement, in vitro models for evaluation of new biomaterials are just emerging and are extremely rare. In this context, there is an increased need for advanced in vitro models, which would best recapitulate the in vivo environment, limiting animal experimentation and adapted to the multitude of these materials. Here, we overview currently available preclinical methods and models for biological in vitro evaluation of new biomaterials. We describe several biological tests used in biocompatibility assessment, which is a primordial step in new material’s development, and discuss existing challenges in this field. In the second part, the emphasis is made on the development of new 3D models and approaches for preclinical evaluation of biomaterials. The third part focuses on the main parameters to consider to achieve the optimal conditions for evaluating biocompatibility; we also overview differences in regulations across different geographical regions and regulatory systems. Finally, we discuss future directions for the development of innovative biomaterial-related assays: in silico models, dynamic testing models, complex multicellular and multiple organ systems, as well as patient-specific personalized testing approaches.
Organoids: opportunities and challenges of cancer therapy
Authors: Jiang Xianjie , Oyang Linda , Peng Qiu , Liu Qiang , Xu Xuemeng , Wu Nayiyuan , Tan Shiming , Yang Wenjuan , Han Yaqian , Lin Jinguan , Xia Longzheng , Peng Mingjing , Tang Yanyan , Luo Xia , Su Min , Shi Yingrui , Zhou Yujuan , Liao Qianjin
Published: July 2023

Organoids are a class of multicellular structures with the capability of self-organizing and the characteristic of original tissues, they are generated from stem cells in 3D culture in vitro. Organoids can mimic the occurrence and progression of original tissues and widely used in disease models in recent years. The ability of tumor organoids to retain characteristic of original tumors make them unique for tumorigenesis and cancer therapy. However, the history of organoid development and the application of organoid technology in cancer therapy are not well understood. In this paper, we reviewed the history of organoids development, the culture methods of tumor organoids establishing and the applications of organoids in cancer research for better understanding the process of tumor development and providing better strategies for cancer therapy. The standardization of organoids cultivation facilitated the large-scale production of tumor organoids. Moreover, it was found that combination of tumor organoids and other cells such as immune cells, fibroblasts and nervous cells would better mimic the microenvironment of tumor progression. This might be important developing directions for tumor organoids in the future.
Efficient implementation of analytical gradients for periodic hybrid functional calculations within fitted numerical atomic orbitals from NAO2GTO
Authors: Qin Xinming , Shang Honghui , Yang Jinlong
Published: July 2023

The NAO2GTO scheme provides an efficient way to evaluate the electron repulsion integrals (ERIs) over numerical atomic orbitals (NAOs) with auxiliary Gaussian-type orbitals (GTOs). However, the NAO2GTO fitting will significantly impact the accuracy and convergence of hybrid functional calculations. To address this issue, here we propose to use the fitted orbitals as a new numerical basis to properly handle the mismatch between NAOs and fitted GTOs. We present an efficient and linear-scaling implementation of analytical gradients of Hartree-Fock exchange (HFX) energy for periodic HSE06 calculations with fitted NAOs in the HONPAS package. In our implementation, the ERIs and their derivatives for HFX matrix and forces are evaluated analytically with the auxiliary GTOs, while other terms are calculated using numerically discretized GTOs. Several integral screening techniques are employed to reduce the number of required ERI derivatives. We benchmark the accuracy and efficiency of our implementation and demonstrate that our results of lattice constants, bulk moduli, and band gaps of several typical semiconductors are in good agreement with the experimental values. We also show that the calculation of HFX forces based on a master-worker dynamic parallel scheme has a very high efficiency and scales linearly with respect to system size. Finally, we study the geometry optimization and polaron formation due to an excess electron in rutile TiO2 by means of HSE06 calculations to further validate the applicability of our implementation.
Searching for atrial fibrillation post stroke: is it time for digital devices?
Authors: Piot Olivier , Guidoux Céline
Published: July 2023

The detection of atrial fibrillation (AF) in patients with cryptogenic stroke (CS) is an essential part of management to limit the risk of recurrence. However, in practice, not all patients who need AF screening are screened, or are screened with significant delays. The disparities of access to examinations, their costs as well as the increasing workload require an evolution of practices both in terms of organization and the type of equipment used. The ubiquity and ease of use of digital devices, together with their evaluation in large population and their expected lower cost, make them attractive as potential alternatives to current equipment at all stages of patient management. However, reliability and accuracy of each digital device for the detection of paroxysmal AF in CS patients should be established before consideration for inclusion in clinical practice. The aim of this short analysis is therefore to review the current practical issues for AF detection in post stroke patients, the potential benefits and issues using digital devices in stroke patients and to position the different digital devices as alternative to standard equipment at each stage of stroke patient pathway. This may help to design future studies for the evaluation of these devices in this context. Under this condition, the time for digital devices to detect AF after stroke seems very close.
Quantifying cellular dynamics in mice using a novel fluorescent division reporter system
Authors: Lukas Eva , Hogan Thea , Williams Cayman , Seddon Benedict , Yates Andrew J.
Published: July 2023

The dynamics of cell populations are frequently studied in vivo using pulse-chase DNA labeling techniques. When combined with mathematical models, the kinetic of label uptake and loss within a population of interest then allows one to estimate rates of cell production and turnover through death or onward differentiation. Here we explore an alternative method of quantifying cellular dynamics, using a cell fate-mapping mouse model in which dividing cells can be induced to constitutively express a fluorescent protein, using a Ki67 reporter construct. We use a pulse-chase approach with this reporter mouse system to measure the lifespans and division rates of naive CD4 and CD8 T cells using a variety of modeling approaches, and show that they are all consistent with estimates derived from other published methods. However we propose that to obtain unbiased parameter estimates and full measures of their uncertainty one should simultaneously model the timecourses of the frequencies of labeled cells within both the population of interest and its precursor. We conclude that Ki67 reporter mice provide a promising system for modeling cellular dynamics.
IL-12/15/18-induced cell death and mitochondrial dynamics of human NK cells
Authors: Terrén Iñigo , Sandá Víctor , Amarilla-Irusta Ainhoa , Lopez-Pardo Ainara , Sevilla Arrate , Astarloa-Pando Gabirel , Amo Laura , Zenarruzabeitia Olatz , Scorrano Luca , Borrego Francisco
Published: July 2023

Natural killer (NK) cells are lymphocytes with potent antitumor functions and, consequently, several NK cell-based strategies have been developed for cancer immunotherapy. A remarkable therapeutic approach is the adoptive transfer of NK cells stimulated with IL-12, IL-15 and IL-18. This cytokine stimulation endows NK cells with properties that resemble immunological memory and, for this reason, they are known as cytokine-induced memory-like (CIML) NK cells. Very promising results have been reported in clinical trials and yet, there are still unknown aspects of CIML NK cells. Here, we have conducted a preliminary study of their mitochondrial dynamics. Our results show that upon IL-12/15/18 stimulation the viability of NK cells decreased and an increment in mitochondrial superoxide levels was observed. In addition, we found that mitochondria appeared slightly elongated and their cristae density decreased following IL-12/15/18 stimulation, possibly in a process mediated by the low levels of optic atrophy type 1 (OPA1) protein. Interestingly, although mitophagy was slightly impaired, an increase in autophagic flux was observed, which might explain the reduced viability and the accumulation of unfit mitochondria. Our findings could be of relevance in order to design new strategies intended to improve the mitochondrial fitness of IL-12/15/18-stimulated NK cells with the aim of improving their therapeutic efficacy.
Response to SARS-CoV-2 initial series and additional dose vaccine in pediatric patients with predominantly antibody deficiency
Authors: Tandon Megha , DiGiacomo Daniel V. , Zhou Baijun , Hesterberg Paul , Rosenberg Chen E. , Barmettler Sara , Farmer Jocelyn R.
Published: July 2023

Data regarding response to SARS-CoV-2 immunization in pediatric patients with predominantly antibody deficiency (PAD) is limited. We evaluated SARS-CoV-2 immunization response by anti-SARS-CoV-2-spike antibody level in 15 pediatric PAD patients. These data were compared to a published cohort of adult PAD patients (n=62) previously analyzed following SARS-CoV-2 immunization at our single center institution. We evaluated demographics, clinical characteristics, immunophenotype, infection history, and past medication use by chart review. Following a two-dose monovalent initial series SARS-CoV-2 immunization, mean anti-SARS-CoV-2-spike antibody levels were significantly higher in pediatric PAD patients compared to adult PAD patients (2,890.7 vs. 140.1 U/mL; p<0.0001). Pediatric PAD patients with low class-switched memory B-cells, defined as <2% of total CD19+ B-cells, had significantly lower mean anti-SARS-CoV-2-spike antibody levels than those without (p=0.02). Following a third-dose monovalent SARS-CoV-2 immunization, the mean anti-SARS-CoV-2-spike antibody levels in pediatric PAD patients significantly increased (2,890.7 to 18,267.2 U/mL; p<0.0001). These data support Centers for Disease Control guidelines regarding three-part SARS-CoV-2 vaccine series, including in the pediatric PAD patient demographic.
Influence of soil nutrients on the presence and distribution of CPR bacteria in a long-term crop rotation experiment
Authors: Santana-Pereira Alinne L. R. , Moen Francesco S. , Severance Beatrice , Liles Mark R.
Published: July 2023

Bacteria affiliated with the Candidate Phyla Radiation (CPR) are a hyper-diverse group of ultra-small bacteria with versatile yet sparse metabolisms. However, most insights into this group come from a surprisingly small number of environments, and recovery of CPR bacteria from soils has been hindered due to their extremely low abundance within complex microbial assemblages. In this study we enriched soil samples from 14 different soil fertility treatments for ultra-small (<0.45 μm) bacteria in order to study rare soil CPR. 42 samples were sequenced, enabling the reconstruction of 27 quality CPR metagenome-assembled genomes (MAGs) further classified as Parcubacteria/Paceibacteria, Saccharibacteria/Saccharimonadia and ABY1, in addition to representative genomes from Gemmatimonadetes, Dependentiae and Chlamydae phyla. These genomes were fully annotated and used to reconstruct the CPR community across all 14 plots. Additionally, for five of these plots, the entire microbiota was reconstructed using 16S amplification, showing that specific soil CPR may form symbiotic relationships with a varied and circumstantial range of hosts. Cullars CPR had a prevalence of enzymes predicted to degrade plant-derived carbohydrates, which suggests they have a role in plant biomass degradation. Parcubacteria appear to be more apt at microfauna necromass degradation. Cullars Saccharibacteria and a Parcubacteria group were shown to carry a possible aerotolerance mechanism coupled with potential for aerobic respiration, which appear to be a unique adaptation to the oxic soil environment. Reconstruction of CPR communities across treatment plots showed that they were not impacted by changes in nutrient levels or microbiota composition, being only impacted by extreme conditions, causing some CPR to dominate the community. These findings corroborate the understanding that soil-dwelling CPR bacteria have a very broad symbiont range and have metabolic capabilities associated to soil environments which allows them to scavenge resources and form resilient communities. The contributions of these microbial dark matter species to soil ecology and plant interactions will be of significant interest in future studies.
Genetic characterization of MDR genomic elements carrying two aac(6′)-aph(2″) genes in feline-derived clinical Enterococcus faecalis isolate
Authors: Li Xue-Song , Qi Yu , Li Peng-hui , Xue Jun-ze , Li Xuan-yu , Muhammad Inam , Li Ya-zhuo , Zhu Dao-mi , Ma Ying , Kong Ling-Cong , Ma Hong-Xia
Published: July 2023

Multidrug-resistant Enterococcus faecalis (E. faecalis) often cause intestinal infections in cats. The aim of this study was to investigate a multidrug-resistant E. faecalis isolate for plasmidic and chromosomal antimicrobial resistance and their genetic environment. E. faecalis strain ESC1 was obtained from the feces of a cat. Antimicrobial susceptibility testing was carried out using the broth microdilution method. Conjugation experiments were performed using Escherichia coli and Staphylococcus aureus as receptors. Complete sequences of chromosomal DNA and plasmids were generated by whole genome sequencing (WGS) and bioinformatics analysis for the presence of drug resistance genes and mobile elements. Multidrug-resistant E. faecalis ESC1 contained a chromosome and three plasmids. The amino acid at position 80 of the parC gene on the chromosome was mutated from serine to isoleucine, and hence the amino acid mutation at this site led to the resistance of ESC1 strain to fluoroquinolones. Eleven antibiotic resistance genes were located on two plasmids. We identified a novel composite transposon carrying two aminoglycoside resistance genes aac(6′)-aph(2″). This study reported the coexistence of a novel 5.4 kb composite transposon and a resistance plasmid with multiple homologous recombination in an isolate of E. faecalis ESC1. This data provides a basis for understanding the genomic signature and antimicrobial resistance mechanisms of this pathogen.
Influence of probiotic supplementation on the growth performance, plasma variables, and ruminal bacterial community of growth-retarded lamb
Authors: Mao Huiling , Ji Wenwen , Yun Yan , Zhang Yanfang , Li Zhefeng , Wang Chong
Published: July 2023

Introduction

Growth-retarded lambs would reduce the economic incomes of sheep farming. Nutritional interventions are supposed to promote gastrointestinal health and the compensatory growth of growth-retarded lambs. This study evaluated the effects of probiotic supplementation on the growth performance, plasma characteristics and ruminal bacterial community of growth-retarded lambs.

Methods

Twenty-four 50-days old male Hu lambs, including 8 healthy lambs (13.2 ± 1.17 kg) and 16 growth-retarded lambs (9.46 ± 0.81 kg), were used in this study. The 8 healthy lambs were fed the basal diet and considered the positive control (GN), and the other 16 growth-retarded lambs were randomly assigned into 2 groups (basal diet without probiotic [negative control, GR] and basal diet supplementation with 1 g/kg concentrate feed probiotic [GRP]), with each group having 4 replicate pens. The feeding trial lasted for 60 days with 7 days for adaptation.

Results

The results showed that dietary supplementation with probiotic increased (p < 0.05) the average daily gain and dry matter intake of growth-retarded lambs. For growth-retarded lambs, supplementation with probiotic increased (p < 0.05) the activities of superoxide dismutase and glutathione peroxidase, as well as the concentrations of growth hormone and immunoglobulin G. Furthermore, the highest (p < 0.05) concentrations of interleukin-6, interferon-gamma and tumor necrosis factor alpha were observed in the GR group. The concentrations of total volatile fatty acids and acetate in growth-retarded lambs were increased by probiotic supplementation (p < 0.05). The relative abundances of Ruminococcus, Succiniclasticum and Acidaminococcus were lower (p < 0.05) in growth-retarded lambs. However, probiotic supplementation increased (p < 0.05) the relative abundances of these three genera.

Discussion

These results indicate that dietary supplementation with probiotic are promising strategies for improving the growth performance of growth-retarded lambs by enhancing immunity and altering the ruminal microbiota.
Molecular epidemiology, risk factors, and outcomes of carbapenem-resistant Klebsiella pneumoniae infection in a tertiary hospital in eastern China: for a retrospective study conducted over 4 years
Authors: Cheng Jun , Zhao Dongmei , Ma Xuejiao , Li Jiabin
Published: July 2023

Objectives

Carbapenem-resistant Klebsiella pneumoniae (CRKP) have been extensively disseminated worldwide, resulting in increased mortality. We performed a retrospective analysis of the epidemiology and risk factors for the outcome of CRKP infection in a general teaching hospital in China.

Methods

A molecular and clinical study was conducted for 98 CRKP in a tertiary hospital from January 2013 to December 2016. Carbapenemase gene detection, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. Logistic regression was also used to identify the risk factors associated with 30-day mortality.

Results

The production of KPC carbapenemase was the main resistant mechanism, and KPC carbapenemase increased annually with a significant difference. However, the molecular outcome revealed the dominance and diversity in CRKP with 24 sequence types (STs) and 59 PFGE types (PTs). The ST11 CRKP strains, which showed a significant increasing trend year by year, were documented as predominant in our study. Additionally, the predominant ST11 CRKP corresponding to PT10 and PT15 continued to exhibit their characteristic patterns. Importantly, the newly identified PT09 and PT16 strains, corresponding to the ST11 lineage, were only discovered in 2016. Meanwhile, factors affecting 30-day mortality and ST11 proportionality with CRKP infection were assessed, and ST11, appropriate empirical treatment, and hospital stays were found to be independently associated with 30-day mortality.

Conclusion

The ST11 CRKP strains played a dominant role in the process; however, the homology of these strains was polymorphic, and the advantage clusters were subject to changes through evolution. Furthermore, in addition to appropriate empirical treatment and hospital stays, ST11 CRKP was independently associated with 30-day mortality. To the best of our knowledge, this association was reported for the first time.
Identification of a novel CNV at the APC gene in a Chinese family with familial adenomatous polyposis
Authors: Li Juyi , He Chengzhi , Gong Jing , Wang Xiufang , Liu Chao , Deng Aiping , Zhu Lin
Published: July 2023

Introduction: Familial adenomatous polyposis (FAP) is the second most commonly inherited colorectal cancer (CRC) predisposition caused by germline mutations within the adenomatous polyposis coli (APC) gene. The molecular defects and clinical manifestations of two FAP families were analyzed, and individual prevention strategies suitable for mutation carriers in different families were proposed.

Methods and results: The pathogenic gene mutations were identified among the two families using whole-exome sequencing and verified with Sanger sequencing or quantitative polymerase chain reaction (qPCR). One novel (GRCh37:Chr5: 112145676–112174368, del, 28,692 bp) and a known (c.C847T:p.R283X) mutation in the APC gene were pathogenic mutations for FAP, according to the sequencing data and tumorigenesis pattern among the family members. The two mutations led to a premature translational stop signal, synthesizing an absent or disrupted protein product.

Conclusion: Our findings expand the known germline mutation spectrum of the APC gene among the Chinese population. This reaffirms the importance of genetic testing in FAP. Genetic consultation and regular follow-ups are necessary for the individualized treatment of cancer-afflicted families with APC expression deficiency. Additional work is required to develop safe and effective chemotherapy and immunotherapy for FAP based on the mutation type.
Pregnancy after kidney transplantation: an observational study on maternal, graft and offspring outcomes in view of current literature
Authors: Stavart Louis , Verly Camille , Venetz Jean-Pierre , Baud David , Legardeur Helene , Vial Yvan , Golshayan Dela
Published: July 2023

Introduction

Pregnancy after kidney transplantation (KTx) is considered to have a high risk of non-negligible complications for the mother, the allograft, and the offspring. With an increased incidence of these pregnancies over the past decades, transplant nephrologists and specialized obstetricians face increasing challenges, with scarce literature regarding long-term outcomes.

Methods

We retrospectively collected data from all women with at least one live birth pregnancy after KTx who were followed at our tertiary hospital between 2000 and 2021 to study maternal, graft and fetal outcomes.

Results

Ten patients underwent 14 live birth pregnancies after KTx. Preponderant maternal complications were stage 1 acute kidney injury (43%), urinary tract infections (UTI, 43%), progression of proteinuria without diagnostic criteria for preeclampsia (29%), and preeclampsia (14%). Median baseline serum creatinine at conception was 126.5 µmol/L [median estimated glomerular filtration rate (eGFR) 49 mL/min/1.73m2], and eGFR tended to be lower than baseline at follow-ups. Overall, there was no increase in preexisting or occurrence of de novo donor-specific antibodies. No graft loss was documented within the 2-year follow-up. There were nine premature births (64%), with a median gestational age of 35.7 weeks. The median birth weight, height, and head circumference were 2,560 g, 45.5 cm, and 32.1 cm, respectively. These measurements tended to improve over time, reaching a higher percentile than at birth, especially in terms of height, but on average remained under the 50th percentile curve.

Discussion

Overall, pregnancies after KTx came with a range of risks for the mother, with a high prevalence of cesarean sections, emergency deliveries, UTI, and preeclampsia, and for the child, with a high proportion of prematurity, lower measurements at birth, and a tendency to stay under the 50th percentile in growth charts. The short- and long-term impact on the allograft seemed reassuring; however, there was a trend toward lower eGFR after pregnancy. With these data, we emphasize the need for a careful examination of individual risks via specialized pre-conception consultations and regular monitoring by a transplant nephrologist and a specialist in maternal–fetal medicine during pregnancy. More data about the long-term development of children are required to fully apprehend the impact of KTx on offspring.
Senolytic therapy is neuroprotective and improves functional outcome long-term after traumatic brain injury in mice
Authors: Wang Jing , Lu Yujiao , Carr Christopher , Dhandapani Krishnan M. , Brann Darrell W.
Published: July 2023

Introduction

Chronic neuroinflammation can exist for months to years following traumatic brain injury (TBI), although the underlying mechanisms remain poorly understood.

Methods

In the current study, we used a controlled cortical impact mouse model of TBI to examine whether proinflammatory senescent cells are present in the brain long-term (months) after TBI and whether ablation of these cells via administration of senolytic drugs can improve long-term functional outcome after TBI. The results revealed that astrocytes and microglia in the cerebral cortex, hippocampus, corpus callosum and lateral posterior thalamus colocalized the senescent cell markers, p16Ink4a or p21Cip1/Waf1 at 5 weeks post injury (5wpi) and 4 months post injury (4mpi) in a controlled cortical impact (CCI) model. Intermittent administration of the senolytic drugs, dasatinib and quercetin (D + Q) beginning 1-month after TBI for 13 weeks significantly ablated p16Ink4a-positive- and p21Cip1/Waf1-positive-cells in the brain of TBI animals, and significantly reduced expression of the major senescence-associated secretory phenotype (SASP) pro-inflammatory factors, interleukin-1β and interleukin-6. Senolytic treatment also significantly attenuated neurodegeneration and enhanced neuron number at 18 weeks after TBI in the ipsilateral cortex, hippocampus, and lateral posterior thalamus. Behavioral testing at 18 weeks after TBI further revealed that senolytic therapy significantly rescued defects in spatial reference memory and recognition memory, as well as depression-like behavior in TBI mice.

Discussion

Taken as a whole, these findings indicate there is robust and widespread induction of senescent cells in the brain long-term after TBI, and that senolytic drug treatment begun 1-month after TBI can efficiently ablate the senescent cells, reduce expression of proinflammatory SASP factors, reduce neurodegeneration, and rescue defects in reference memory, recognition memory, and depressive behavior.
Efficacy of opioids for traumatic pain in the emergency department: a systematic review and Bayesian network meta-analysis
Authors: Fu Yawen , Liu Qiang , Nie Hu
Published: July 2023

Aim: To systematically assess and rank the efficacy of opioid medications for traumatic pain in the emergency department in terms of pain relief, adverse events and rescue analgesia.

Methods: Four databases were systematically searched until 26 September 2022: PubMed, Embase, Cochrane Library, and Web of Science. Outcomes were pain relief, adverse events (dizziness, hypotension, pruritus, sedation), and rescue analgesia. For each outcome, network plots were drawn to exhibit direct and indirect comparisons, and rank probabilities were utilized to rank the efficacy of different opioids.

Results: Twenty studies of 3,040 patients were eligible for this network meta-analysis. According to the rank probabilities, the top three analgesic medications for pain relief may be sufentanil (78.29% probability of ranking first), buprenorphine (48.54% probability of ranking second) and fentanyl (53.25% probability of ranking third); buprenorphine (31.20%), fentanyl (20.14%) and sufentanil (21.55%) were least likely to cause dizziness; the top three analgesic medications which were least likely to cause hypotension were buprenorphine (81.64%), morphine (45.02%) and sufentanil (17.27%); butorphanol (40.56%), morphine (41.11%) and fentanyl (14.63%) were least likely to cause pruritus; the top three medications which were least likely to cause sedation were hydrocodone + acetaminophen (97.92%), morphine (61.85%) and butorphanol (55.24%); patients who received oxycodone (83.64%), butorphanol (38.31%) and fentanyl (25.91%) were least likely to need rescue analgesia in sequence.

Conclusion: Sufentanil, buprenorphine and fentanyl may be superior to other opioid medications in terms of pain relief and the incidence of dizziness, hypotension and pruritus, which might be selected as opioid analgesics for traumatic pain in the emergency setting.